Prescribing drugs of dependence in general practice

Part C2 - The role of opioids in pain management - Chapter 6

Overview of opioid analgesics

Last revised: 02 Jun 2020

There are significant difficulties translating evidence from clinical pain trials into pain management in practice. This is not only because of issues around the number, quality, bias, duration and construction of studies,90,96,286 but also because pain is a subjective experience influenced by a complex range of factors.

Additionally, labels such as CNCP do not just describe one condition, but a variety of conditions with diverse aetiologies, for which the evidence for therapeutic impact varies. Patients with the same condition will have unique pain experiences and respond differently to therapeutic interventions.

No analgesic drug works well in all patients. Most analgesics work well in a small proportion of patients. There is often a strong placebo (contextual) effect. Pain relief from therapeutic interventions is not normally distributed but is usually bimodal, being either very good (above 50%) or poor (below 15%).287–289 Hence, using averages is unhelpful and misleading because few (if any) patients experience ‘average’ pain relief and it tells us nothing about how many patients will experience clinically useful analgesia.221

Clinical trials designed for regulatory purposes consider single interventions and fixed dose regimens, which may exacerbate adverse events and withdrawals, resulting in higher failure rates.221 For example:

  • failure rates for NSAIDs are ≥70% in osteoarthritis, ≥80% in chronic low back pain and 58–72% in ankylosing spondylitis221
  • for neuropathic conditions, antidepressants and anticonvulsants have failure rates of ≥70% in painful diabetic neuropathy and post-herpetic neuralgia, and ≥87% in fibromyalgia.221

This does not reflect the clinical reality of choosing options and individualising doses. For example, about half of osteoarthritis patients with moderate or severe pain on treatment had a significant (30%) reduction in pain intensity when switched to another NSAID.290

On review of pain trial studies, it was noted that patient response distributions are U-shaped, not Gaussian, making average values inappropriate. In fact, the ‘average pain score’ data may mislead. Since 2011, the editors of the Cochrane Pain, Palliative and Supportive Care Systematic Review Group have established new criteria for examining evidence in pain.291 It is now standard to measure ‘responder’ analyses; reporting the proportion of patients achieving outcomes that patients consider worthwhile221 (that is, the proportion of patients who experience at least 30–50% pain reduction).

A minority of patients achieve very large reductions in pain (responders) whereas the majority achieve little relief (non-responders).292 Individual patient analyses for chronic pain interventions have shown that people who respond also experience improvements in fatigue, depression, and sleep interference.53,293

It is standard for patients to delegate ‘at least 50% pain reduction’ as a successful outcome. It is the minimum outcome that patients want,293 and may be associated with restoration of function, work, and quality of life lost with chronic pain.29 Clinically, this has major implications for practice. Use of responder analysis changes judgement of benefit and risk and suggests that classical trials in pain using ‘averages’ may underestimate efficacy.221

Responder analysis also supports clinical practice focus on individual responses to therapy. It enables trialling numerous treatment options to achieve pain relief for the individual.221 Similarly, non-responders should stop treatment that does not work.

The evidence of failure for paracetamol295 and NSAIDs296,297 in musculoskeletal pain and the poor efficacy for opioids, anticonvulsants (gabapentin, pregabalin) and antidepressants for neuropathic pains100 need to be reconsidered in the light of responders and non-responders. Evidence about a single intervention needs to be considered with individual patient circumstances, tempered with wisdom and experience to be used sensibly in clinical setting.286

It is with these caveats in mind that evidence of effect of pain medications in chronic pain should be considered.

The efficacy of opioid therapy in acute pain is supported by strong evidence from RCTs5,7 and by systematic reviews in cancer pain,298,299 palliative care300 and opioid dependence.301

CNCP is very different. It is not a diagnosis, but a group of entities with various aetiologies. The pathophysiologic descriptors of these aetiologies are still changing. Studies examining chronic pain often have methodological weaknesses that make interpretation difficult, and transfer into clinical practice requires care.

The evidence on long-term opioid therapy for chronic pain outside of end-of-life care remains limited; however, this does not mean there is no evidence to guide care.

Evidence in different chronic pain conditions

Musculoskeletal pain

Musculoskeletal conditions account for a large proportion of general practice opioid prescriptions.302 In trials with at least 12 weeks’ duration of opioids for managing osteoarthritis, there is:

  • fair evidence for tramadol303
  • limited evidence for transdermal buprenorphine303 – it has been shown to be effective and well tolerated (with analgesic effects similar to tramadol)304
  • limited evidence for tapentadol for arthritic pain.303,305

Reviews of opioid therapy in chronic low back pain provide some support for short-term use, but evidence beyond three months is lacking.306,307 In trials with at least 12 weeks’ duration of opioids for managing chronic low back pain, there is some evidence for transdermal buprenorphine,308 tapentadol305 and tramadol/paracetamol combinations.309–311

Caution should be used in extrapolating evidence from short-term trials into longer-term care. Analysis of openlabel extension trials provides some support for sustained opioid effect, but in only 25% of patients originally enrolled.312 The harms (abuse of prescribed opioids, mortality) of long-term opioid therapy in clinical practice are underestimated by long-term extension studies, probably because patients with major medical diseases and mental disorders were excluded.312

Neuropathic pain

Several guidelines support opioid use in neuropathic pain, but not as a first-line treatment. When first-line medications fail or provide inadequate pain relief, tramadol or a conventional opioid analgesic may be useful as a second-line or third-line treatment.94,96 For management of neuropathic pain:

  • tramadol has weak GRADE recommendations for its use; generally it is considered a second-line treatment  because of safety and tolerability.96 The tramadol NNT for 50% pain reduction is approximately five96
  • strong opioids, particularly oxycodone and morphine, have weak GRADE recommendations for use and are recommended as third-line treatments mainly because of safety concerns.96 The oxycodone NNT for 50% pain reduction is approximately four.96 Other reviews are less favourable for oxycodone and report a moderate benefit (at least 30% pain relief) NNT at 5.7.313

The NNT for benefit in opioids appears similar to other drugs (eg antidepressants, anticonvulsants) used in painful neuropathies such as diabetic neuropathy, post-herpetic neuralgia, peripheral nerve injury, HIV neuropathy, central pain, trigeminal neuralgia and mixed neuropathic pain. The NNT for these non-opioid medications range from around four to eight. Continual critical appraisal of all classes of medication used in long-term pain management is warranted.

Combination therapies are common though few are studied. One meta-analysis demonstrated modest superiority of gabapentin plus opioid versus gabapentin alone, although the combination produced significantly more dropouts due to accentuated side effects related to combination treatments.314

Summary

There is limited evidence for opioids for management of CNCP and insufficient evidence to determine long-term benefits. For well-selected patients with no history of SUDs, proper management with opioids can contribute to long-term pain relief.11However, long-term opioid treatment (≥26 weeks) benefits only about 25%

Presented in alphabetical order

Buprenorphine

Buprenorphine is a partial agonist at mu opioid receptors and an antagonist at delta and kappa receptors. It is typically used for analgesia (in low-dose patch formulation) and in ORT, where sublingual formulations are usually used.

Musculoskeletal pain

There is limited evidence regarding buprenorphine for CNCP due to a lack of high-quality RCTs.303 However, transdermal buprenorphine for osteoarthritis has been shown to be effective and well tolerated, with analgesic effects similar to tramadol.304

Neuropathic pain

Case reports suggest that buprenorphine is effective in peripheral315,316 and central neuropathic pain in the clinical setting.317 However, large trials are lacking and currently there is not enough evidence to support or dispute efficacy of buprenorphine in any neuropathic pain condition.318

Addiction medicine

Buprenorphine is listed for use in ORT (as Section100 [S100]).

In practice

Buprenorphine is PBS listed for chronic severe pain and ORT.

Transdermal patches (used for pain, not ORT) generally provide a week of analgesia. Occasionally, patients complain that there is release of the drug from the transdermal patch for only six, or rarely five, days. In these instances, the patches may need to be changed more frequently than weekly.

Buprenorphine can be safely used in patients with renal impairment and has less immunosuppressive effect than pure mu-opioid agonists.319

As long as sedative medication is not given concurrently, the risk of respiratory depression with buprenorphine is low compared to morphine, methadone, hydromorphone and fentanyl.320 There is a ceiling effect for respiratory depression but not for analgesia.321 If buprenorphine-induced respiratory depression occurs it may be completely reversed with naloxone,319 although higher than usual doses and a longer duration infusion of naloxone are required.322

Withdrawal symptoms may occur if buprenorphine is ceased after long-term treatment; however, these symptoms are milder and more delayed in onset (≥72 hours) compared with other opioids.320

Buprenorphine binds strongly to the mu receptor site, but does not fully activate it.323 Therefore, if buprenorphine is combined with pure mu agonists (eg morphine, fentanyl), interactions may occur. For example, if a pure mu agonist is given to a person on maintenance buprenorphine it may be less effective. Conversely, buprenorphine could theoretically cause a withdrawal reaction if given to a patient taking longer-term opioid (mu) therapy.323

Antagonism of response to pure mu agonists (precipitated withdrawal) can occur with buprenorphine but it has only been demonstrated at buprenorphine doses exceeding the ranges used for analgesia (eg at dosages for ORT). In practice, these drug interactions are unlikely.

Codeine

Codeine is a weak mu receptor agonist (200-fold weaker affinity than morphine) and its analgesic action depends on the metabolism of about 10% of the dose to morphine, via CYP2D6.324,325 Ultrarapid metabolisers have significantly higher levels of morphine and morphine metabolites after the same dose of codeine.326 Poor metabolisers do not produce any morphine or gain any analgesic effect.

Codeine is subject to misuse and dependence, and is the commonest prescription opioid associated with fatal overdoses in Victoria.327 Rates of misuse average between 21% and 29%, and dependence average between 8% and 12%.327

Musculoskeletal pain

Codeine is commonly used in combination with other minor analgesics (eg paracetamol, ibuprofen). There is highquality evidence that combination codeine medicines provide clinically important pain relief in the immediate term, but this is mostly in acute pain.16

In practice

Codeine is classified as a weak opioid. It is listed by the PBS for mild to moderate pain. There is no role for codeine in chronic pain.

A single 60 mg dose provides good analgesia to few adults: 12 patients need to be treated for one to achieve a 50% reduction in postoperative pain.328 OTC preparations containing low doses of 8–15 mg codeine phosphate are considered sub-therapeutic.

Combining codeine with non-opioid analgesics provides limited additional analgesic benefit: seven patients need to be treated with ibuprofen 400 mg/codeine 25.6–60 mg for one to obtain at least a 50% reduction in postoperative pain when compared to treatment with ibuprofen 400 mg alone.328,329

Given the variability in response and risk of harm, use of codeine should be closely monitored.

Dextropropoxyphene

In November 2011, the TGA decided to remove the registration of dextropropoxyphene in Australia.330 It was withdrawn from the Food and Drug Administration (FDA) in the US due to risks of QT-interval prolongation and possibility of Torsades de Pointes (TdP) and cardiogenic death.

Oral dextropropoxyphene alone is a poorly effective analgesic.331 In combination with paracetamol, it also provides little benefit above paracetamol alone.332

In practice

Dextropropoxyphene has now been limited to authorised users for previous users only. To prescribe this medication, GPs need to:

  • be aware that the medicine is only approved for use in patients not able to be adequately treated with other mild pain killers
  • have considered the contraindications for the medicine outlined in the product information and have explained them to the patient at the time of prescribing
  • have considered any recent changes to the patient’s clinical presentation or biochemical status
  • have warned the patient at the time of prescribing about appropriate use of the medicine
  • be satisfied at the time of prescribing that the patient’s history does not indicate that the patient is at risk of accidental or intentional self-harm.

The conditions also require that a signed Prescriber Confirmation form is presented to the pharmacist dispensing these medicines before supplying them to the patient every time a patient presents for a prescription.

Fentanyl

Fentanyl is a highly potent opioid, which is active at the mu receptor. It is metabolised almost exclusively in the liver to minimally active metabolites. This makes it particularly useful in renal failure: <10% of unmetabolised fentanyl is renally excreted.333

It is available as transdermal patches, oral transmucosal lozenges or lollipops and injectable preparations. The transdermal system offers an excellent option for long-term treatment of cancer pain, but the RACGP believes it is not suitable for CNCP. A 25 ug/hour fentanyl patch is equivalent to approximately 90 mg of oral morphine per day. Oral transmucosal fentanyl rapidly achieves high plasma concentrations and is indicated to treat breakthrough pain in cancer patients who are not opioid naïve.333

Fentanyl-related mortality is currently relatively low in Australia compared to the US and parts of Europe. However, fentanyl misuse is on the rise in Australia with a large proportion of these deaths occurring among at-risk groups who inject drugs.334 Because of the misuse potential, this drug should be used only as indicated. It has known diversional potential, extremely high street value and risk of misuse.

In practice

Fentanyl is PBS listed for severe disabling pain and is usually used in cancer care or in acute hospital settings.

In the opioid-naïve patient, there is a significant risk of toxicity and overdose. Fentanyl patches are not suitable to be used as the initial agent in the management of pain for opioid-naïve patients due to high morphine-equivalent doses. Fentanyl should only be used in the case of cancer pain when all other options have been exhausted.

Be aware that local heat (eg hydrotherapy pool) may increase absorption from the patch.

Hydromorphone

Hydromorphone is an effective strong opioid acting as a mu receptor agonist. It is approximately five times as potent as morphine and provides slightly better clinical analgesia than morphine, but has similar adverse effects.335,336 The main metabolite of hydromorphone is hydromorphone-3-glucuronide (H3G), which is dependent on the kidneys for excretion, has no analgesic action and can lead to dose-dependent neurotoxic effects.337

It is available as solution for injection, oral liquid and tablets. It also has extremely high potential for misuse and high street value for those who divert this drug.

In practice

Hydromorphone is PBS listed for severe disabling pain, but in practice is usually restricted to malignant pain, or patients undergoing dialysis. It is not suitable to be used as the initial agent in the management of pain for opioidnaïve patients.

Methadone

Methadone is a synthetic opioid acting as an agonist at the mu receptor with additional ketamine-like antagonism at the N-methyl-D-aspartate receptor. It is commonly used for the maintenance treatment of patients with an addiction to opioids and in patients with chronic pain.

It has good oral bioavailability (70–80%), high potency, a long duration of action and no active metabolites.338 But it also has a long and unpredictable half-life (mean of 22 hours; range 4–190 hours), which increases the risk of accumulation.339

Concurrent administration of other drugs that are metabolised by the P450 enzyme system may have significant effects. P450 inducers (eg carbamazepine, rifampicin, phenytoin, St John’s wort (Hypericum perforatum), some antiretroviral agents) may increase methadone metabolism, which lowers methadone blood levels and leads to potential reduced efficacy or even withdrawal.340 Use of P450 inhibitors (eg other antiretroviral agents, some SSRIs, grapefruit juice, antifungal agents) may lead to raised methadone levels, which increases risk of adverse effects or overdose.340 Checking for drug interactions with methadone can be done online.

In practice

Methadone is PBS listed for severe disabling pain and for ORT (as S100). Two formulations are available in Australia. Methadone liquid is used once daily for maintenance in opioid dependent patients. Methadone tablets may be used two to four times daily to manage persistent pain.341

Methadone use is usually confined to specialist pain medicine areas342 as it has complicated and unpredictable pharmacokinetics. Extreme caution must be taken when inducting a person onto an appropriate dose of methadone, with a slow titration regimen and close monitoring required. It may take up to two weeks to reach steady state levels, and drug accumulation may cause excessive sedation and high risk of overdose and death if the dose is increased rapidly.341

Morphine

Morphine has been the most widely used opioid in acute, persistent and cancer pain, and remains the standard against which other opioids are compared.

The main metabolites of morphine (primarily formed by hepatic glucuronidation) are morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G). M6G is a mu opioid receptor agonist and is the main mediator of analgesia.343 M3G has very low affinity for opioid receptors and no analgesic activity, but may be responsible for the neurotoxic symptoms such as hyperalgesia, allodynia and myoclonus, sometimes associated with high doses of morphine.325 Both metabolites are renally eliminated.

Higher doses, older age, impaired renal function and the oral administration (due to first-pass metabolism) are associated with higher M3G and M6G concentrations and therefore with the potential risk of severe long-lasting sedation and respiratory depression.344,345

While the clinical significance is uncertain, morphine is the most immunosuppressive of the currently available opioids.346,347

There has been a decrease in morphine prescribing in Australia.334 Prescriptions are most prevalent among older Australians.

Musculoskeletal pain

The evidence for morphine in managing CNCP, including low back pain, is poor.303

Neuropathic pain

Strong opioids including morphine have weak GRADE recommendations for use and are recommended as third line mainly because of safety concerns.96

In practice

Morphine formulations are indicated by the PBS for severe disabling pain (cancer, palliative care) and chronic severe pain. Commencement doses vary according to patient selection and age.

Oxycodone

Oxycodone action appears to be mediated primarily by mu receptor agonism. Oxycodone contributes the majority of drug effect, as its metabolites, noroxycodone and oxymorphone (via CYP3A4), are only weakly active. However, oxycodone concentration may be dependent on CYP2D6 activity, resulting in ultrarapid metabolisers experiencing better analgesic effects than poor metabolisers, but also higher toxicity.348,349

Paradoxically, in acute postoperative pain, the CYP2D6 genotype does not appear to influence oxycodone requirements.350 There is an increasing use of oxycodone in the acute, hospital and perioperative settings as it has a faster onset of action than morphine, better oral bioavailability, longer duration of action, fewer concerns about metabolites and lower rate of adverse effects based on these pharmacological properties.350–352

Oxycodone-related deaths are currently relatively low in Australia; they are not comparable to numbers reported in the US.334

Musculoskeletal pain

The evidence for oxycodone in the management of CNCP is poor.303

Neuropathic pain

Strong opioids including oxycodone have weak GRADE recommendations for use and are recommended as third line mainly because of safety concerns.96

In practice

Oxycodone is PBS listed for severe disabling pain and chronic severe pain. It is particularly popular in hospital and acute pain settings. Care should be used in rehabilitation settings to minimise chronic use.

Care should also be taken by GPs continuing to prescribe oxycodone in the community post discharge from the hospital setting. All patients should have plans to be weaned off their opioid analgesics post discharge.

The use of oxycodone is increasing rapidly and addiction specialists report that it is often a drug of choice for misuse. A combination of oxycodone with naloxone has recently been released in Australia. This combination substantially reduces the chance of constipation,353 but the risks of misuse and diversion still exist.

Note that St John’s wort (H. perforatum) induces metabolism of oxycodone, significantly reducing its plasma concentrations and efficacy.354

Pethidine

Pethidine is a synthetic opioid active at the mu receptor. IM pethidine has been widely used in Australia for a range of pain problems. Its use is decreasing because of multiple disadvantages compared to other opioids. Repeated dosing or renal failure leads to accumulation of its active metabolite (norpethidine), which is associated with neuroexcitatory effects that range from nervousness to tremors, twitches, multifocal myoclonus and seizures.355

When used parenterally, pethidine does not provide better analgesia than morphine, but does induce more nausea and vomiting than morphine.356

In practice

Use of pethidine is discouraged in favour of other opioids.357,358

It has high addiction potential and is not recommended for the treatment of persistent pain.

Pethidine is no longer indicated for the treatment of migraines.

Tapentadol

Tapentadol is a combined weak mu agonist and noradrenaline reuptake inhibitor (acting on descending pain inhibition pathways) with no active metabolites.359–361 In a number of chronic pain conditions, tapentadol shows efficacy that is comparable or better than conventional opioids but with reduced rates of gastrointestinal adverse effects (eg nausea, vomiting, constipation), which results in less treatment discontinuation.362

At doses up to the maximum recommended 500 mg/day, tapentadol has no effect on heart rate or blood pressure due to noradrenaline reuptake inhibition, even in patients with hypertension and/or on antihypertensives.363 However, as it is metabolised by the liver, impaired hepatic function may require dose adjustment.364

Despite widespread use over several years in the US and Europe, there are only two reported cases of an overdose death.365 Although it is a controlled medicine in all countries, tapentadol shows a lower rate of misuse and diversion than oxycodone and hydrocodone and a rate comparable to tramadol.366,367 There are limited data to support a role for tapentadol in cancer pain.368

Musculoskeletal pain

Currently, relatively few RCTs have studied tapentadol. There is evidence of benefit in osteoarthritis, low back pain and postoperative pain.305,369–371 Three randomised trials studying tapentadol for managing chronic pain of osteoarthritis and low back found that 32% of patients received greater than 50% pain relief.303

Neuropathic pain

Due to effect of noradrenaline uptake inhibition on descending pathways of pain, tapentadol modulates increased conditioned pain seen with neuropathic pain.372 This effect has been confirmed in diabetic neuropathy.360

In practice

Tapentadol is PBS listed for chronic severe pain.

Start at low dose 50 mg and titrate the dose according to response increase: every three days, increase the dose by 50 mg for each twice-daily dose until adequate analgesia or the 50 mg OME dose of 125 mg/day is reached.

Tramadol

Tramadol acts as both a weak opioid agonist and as a serotonin and noradrenaline reuptake inhibitor. Due to the combined effects, it is commonly referred to as an atypical centrally acting analgesic.361,373

Tramadol is metabolised by CYP2D6 to an active metabolite, O-desmethyltramadol (M1), which is a more potent mu opioid receptor agonist than the parent drug.374 Hence, patients who are poor metabolisers receive less analgesic effect from tramadol.375

The adverse-effect profile of tramadol is different from other opioids. The most common side effects are nausea and vomiting, which occur at rates similar to morphine.376,377 However, tramadol has less effect on gastrointestinal motor function than morphine.377,378 It causes less respiratory depression than other opioids at equianalgesic doses.379,380 Tramadol does not increase the incidence of seizures compared with other analgesic agents,381,382 although there is a risk of inducing serotonin toxicity when tramadol is combined with other serotonergic medicines, in particular SSRIs.383

Tramadol has a lower potential for misuse than conventional opioids.384

Musculoskeletal pain

There is fair evidence for tramadol in managing osteoarthritis.303

Neuropathic pain

Tramadol has a weak GRADE recommendation for use in neuropathic pain,96 and is regarded as generally second line because due to tolerability and safety.96,385

In practice

Tramadol is listed on the PBS for acute or chronic pain not responding to aspirin and/or paracetamol; short-term treatment of acute pain.

Side effects often limit use, but tramadol can be useful if tolerated.

Formulations

The practical usefulness of opioids is related to the available formulations (Table 10).

Approximate equivalence doses

Oral morphine is the standard that other opioids are measured against. Full opioid agonists given in equianalgesic doses produce the same analgesic effect.387 However, accurate determination of equianalgesic doses is difficult due to individual variability in pharmacokinetics and dynamics.147

There are several published tables providing approximate equianalgesic doses. These are typically based on singledose studies in opioid-naïve subjects and may not be as relevant when conversions are made after repeated doses of an opioid.337 They also do not take into account incomplete cross-tolerance and patient-specific factors.342 

Converting to methadone requires special caution. Regardless of how much other opioid the patient is being prescribed, commence methadone at low doses in accordance with the National guidelines for medicationassisted treatment for opioid dependence  or in consultation with pain or addiction specialists.

Box 13.

Useful tools for calculating equivalent doses

Commencing and increasing dosage

Starting doses are a guide only and may vary according to the clinical situation, condition of the patient and previous analgesic requirements. For example, older patients generally require lower opioid doses.388

At each review, assess pain intensity, cardiorespiratory status, level of sedation and other adverse effects. Titrate dose according to response, sedation score (an early indicator of respiratory depression) and respiratory rate. Use small dose increments as the dose required may vary more than 10-fold between patients of similar age, irrespective of weight.388

Adjust the dose of controlled-release (CR) opioids, not the frequency of administration. However, if increasing the dose fails, it may occasionally be appropriate to administer doses more frequently for patients with pain that regularly occurs shortly before the next dose is due.388

Opioid ceiling doses

Use caution when prescribing opioids at any dosage. Many harms are dose related, so aim for the lowest effective dose then carefully reassess for evidence of individual benefits and risks, especially when increasing dosage to 50 mg OME or more per day. GPs must be able to justify a decision to titrate dosage to 100 mg or more OME per day and should avoid increasing dosage to 100 mg or more OME per day without specialist involvement.8 Higher opioid doses may be acceptable in cancer-related pain.


 

Tolerance is a predictable state of adaption in which exposure to a drug induces changes that result in diminution of one or more of the drug’s effects over time.389 The patient become ‘desensitised’ to the drug and increased doses are then needed to get the same effect.

The decrease in the effectiveness of opioid analgesia has traditionally been attributed to opioid tolerance (a desensitisation of anti-nociceptive pathways to opioids). However, it is now known that administration of opioids can also result in opioid-induced hyperalgesia (OIH), which is a sensitisation of pro-nociceptive pathways leading to pain hypersensitivity. Both tolerance and OIH can significantly reduce the analgesic effect of opioids.390,391

The predictable and physiological decrease in the effect of a drug over time may be referred to as ‘pharmacological tolerance’. ‘Apparent tolerance’ occurs when both tolerance and OIH contribute to a decrease in the effectiveness of opioids.392,393

There is some evidence that administration of ‘commonly used’ dosages of oral opioids does not result in abnormal pain sensitivity.394

In an individual patient displaying decreased effectiveness of opioid therapy, it can be impossible to determine whether tolerance or OIH is causing a reduction in pain control, creating a management dilemma: inadequate pain relief due to tolerance may improve with opioid dose escalation, while improvements in analgesia in the presence of OIH may follow a reduction in opioid dose.392 The only reasonable action in these circumstances is to reduce opioid doses.

Tolerance also occurs to some of the adverse effects of opioids. Rapid tolerance may develop to sedation, cognitive effects, nausea and respiratory depression. However, there is little, if any, change in miosis or constipation.392

‘Dependence’ has historically been defined in pharmacological terms: a time-limited state that develops during chronic drug treatment in which cessation elicits an abstinence reaction (withdrawal) and is reversed by renewed administration of the drug.157

Opioid withdrawal syndrome is characterised by signs and symptoms of sympathetic stimulation due to decreased sympathetic antagonism by opioids (Table 12).157 Symptoms start two to three half-lives after the last dose of opioid. For example, oxycodone has a half-life of 3–4 hours: symptoms would start after 6–12 hours, peak at approximately 48–72 hours, and resolve within 7–14 days.157 Timelines and symptoms vary depending on the duration of action,19 specific dose, speed of taper, and duration of use.157

Withdrawal can be minimised by gradual reduction of opioid use. Where it does occur, unless a patient has significant comorbidity or is otherwise medically unstable, withdrawal is not life threatening, although it may be very distressing.19,157 Acute withdrawal (when opioids are stopped suddenly, or an antagonist such as naloxone or naltrexone is administered) should be treated by reintroducing opioids or by IV fluids, glucose, and adrenergic-blocking drugs. Clonidine is useful in this situation.157 Reassurance and comfort measures may also be required.157

Common opioid-related adverse effects are sedation, pruritus, nausea, vomiting, slowing of gastrointestinal function and urinary retention.395–397 Uncommonly, opioids (methadone, oxycodone) are associated with prolonged QT-interval with a risk of TdP and cardiac arrest.398,399 These effects are dose related.

  1. Cohen M, Quintner J, Buchanan D. Is chronic pain a disease? Pain Med 2013;14(9):1284–88.
  2. Upshur CC, Luckmann RS, Savageau JA. Primary care provider concerns about management of chronic pain in community clinic populations. J Gen Intern Med 2006;21(6):652–55.
  3. Henderson JV, Harrison CM, Britt HC, Bayram CF, Miller GC. Prevalence, causes, severity, impact, and management of chronic pain in Australian general practice patients. Pain Med 2013;14(9):1346–61.
  4. O’Rorke JE, Chen I, Genao I, Panda M, Cykert S. Physicians’ comfort in caring for patients with chronic nonmalignant pain. Am J Med Sci 2007;333(2):93–100.
  5. Australian and New Zealand College of Anaesthetists. Recommendations regarding the use of opioid analgesics in patients with chronic non-cancer pain. Melbourne: ANZCA, 2015 PM1-2010.pdf [Accessed 19 July 2017].
  6. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: An emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336(7650):924–26. [Accessed 19 July 2017].
  7. Schug S, Palmer G, Scott D, et al. Acute pain management: Scientific evidence. 4th edn. Melbourne: ANZCA, 2015 Documents/APMSE4_2015_Final [Accessed 19 July 2017].
  8. Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain – United States, 2016. JAMA 2016;315(15):1624–45. [Accessed 19 July 2017].
  9. Saragiotto BT, Machado GC, Ferreira ML, Pinheiro MB, Abdel Shaheed C, Maher CG. Paracetamol for low back pain. Cochrane Database Syst Rev 2016(6):CD012230. [Accessed 19 July 2017].
  10. Williams CM, Maher CG, Latimer J, et al. Efficacy of paracetamol for acute low-back pain: A double-blind, randomised controlled trial. Lancet 2014;384(9954):1586–96. [Accessed 19 July 2017].
  11. Moore RA, Derry S, Aldington D, Wiffen PJ. Single dose oral analgesics for acute postoperative pain in adults – An overview of Cochrane reviews. Cochrane Database Syst Rev 2015(9):CD008659. [Accessed 19 July 2017].
  12. Moore RA, Derry S, Wiffen PJ, Straube S, Aldington DJ. Overview review: Comparative efficacy of oral ibuprofen and paracetamol (acetaminophen) across acute and chronic pain conditions. Eur J Pain 2015;19(9):1213–23. [Accessed 19 July 2017].
  13. Moore RA, Derry S, Aldington D, Wiffen PJ. Adverse events associated with single dose oral analgesics for acute postoperative pain in adults – An overview of Cochrane reviews. Cochrane Database Syst Rev 2015(10):CD011407. [Accessed 19 July 2017].
  14. Ong CK, Seymour RA, Lirk P, Merry AF. Combining paracetamol (acetaminophen) with nonsteroidal antiinflammatory drugs: A qualitative systematic review of analgesic efficacy for acute postoperative pain. Anesth Analg 2010;110(4):1170–79. [Accessed 19 July 2017].
  15. Bailey E, Worthington HV, van Wijk A, Yates JM, Coulthard P, Afzal Z. Ibuprofen and/or paracetamol (acetaminophen) for pain relief after surgical removal of lower wisdom teeth. Cochrane Database Syst Rev 2013;12:CD004624. [Accessed 19 July 2017].
  16. Shaheed CA, Maher CG, McLachlan AJ. Investigating the efficacy and safety of over-the-counter codeine containing combination analgesics for pain and codeine based antitussives. Canberra: Therapeutic Goods Association, 2016 [Accessed 19 July 2017].
  17. Blondell RD, Azadfard M, Wisniewski AM. Pharmacologic therapy for acute pain. Am Fam Physician 2013;87(11):766–72. [Accessed 19 July 2017].
  18. Bendtsen L, Evers S, Linde M, et al. EFNS guideline on the treatment of tension-type headache – Report of an EFNS task force. Eur J Neurol 2010;17(11):1318–25. [Accessed 19 July 2017].
  19. Thorson D, Biewen P, Bonte B, et al. Acute pain assessment and opioid prescribing protocol. Bloomington, MN: Institute for Clinical Systems Improvement, 2014 Opioids.pdf [Accessed 1 September 2017].
  20. Australian and New Zealand College of Anaesthetists. Guidelines on acute pain management. Melbourne: ANZCA, 2013 Documents/ps41-2013-guidelines-on-acute-painmanagement [Accessed 19 July 2017].
  21. Traeger AC, Hubscher M, Henschke N, Moseley GL, Lee H, McAuley JH. Effect of primary care-based education on reassurance in patients with acute low back pain: Systematic review and meta-analysis. JAMA Intern Med 2015;175(5):733–43. [Accessed 19 July 2017].
  22. Qaseem A, Wilt TJ, McLean RM, Forciea MA, Clinical Guidelines Committee of the American College of Physicians. Noninvasive treatments for acute, subacute, and chronic low back pain: A clinical practice guideline from the American College of Physicians. Ann Intern Med 2017;166(7):514–30. [Accessed 19 July 2017].
  23. Chung JW, Zeng Y, Wong TK. Drug therapy for the treatment of chronic nonspecific low back pain: Systematic review and meta-analysis. Pain Physician 2013;16(6):E685–704. [Accessed 19 July 2017].
  24. van den Bekerom MP, Sjer A, Somford MP, Bulstra GH, Struijs PA, Kerkhoffs GM. Non-steroidal anti-inflammatory drugs (NSAIDs) for treating acute ankle sprains in adults: Benefits outweigh adverse events. Knee Surg Sports Traumatol Arthrosc 2015;23(8):2390–99. [Accessed 19 July 2017].
  25. Massey T, Derry S, Moore RA, McQuay HJ. Topical NSAIDs for acute pain in adults. Cochrane Database Syst Rev 2010(6):CD007402. [Accessed 19 July 2017].
  26. Predel HG, Giannetti B, Seigfried B, Novellini R, Menke G. A randomized, double-blind, placebo-controlled multicentre study to evaluate the efficacy and safety of diclofenac 4% [Accessed 19 July 2017].
  27. spray gel in the treatment of acute uncomplicated ankle sprain. J Int Med Res 2013;41(4):1187–202. [Accessed 19 July 2017].
  28. Predel HG, Hamelsky S, Gold M, Giannetti B. Efficacy and safety of diclofenac diethylamine 2.32% gel in acute ankle sprain. Med Sci Sports Exerc 2012;44(9):1629–36. [Accessed 19 July 2017].
  29. Serinken M, Eken C, Turkcuer I, Elicabuk H, Uyanik E, Schultz CH. Intravenous paracetamol versus morphine for renal colic in the emergency department: A randomised double-blind controlled trial. Emerg Med J 2012;29(11):902–95. [Accessed 19 July 2017].
  30. Holdgate A, Pollock T. Nonsteroidal anti-inflammatory drugs (NSAIDs) versus opioids for acute renal colic. Cochrane Database Syst Rev 2005(2):CD004137. [Accessed 19 July 2017].
  31. Afshar K, Jafari S, Marks AJ, Eftekhari A, MacNeily AE. Nonsteroidal anti-inflammatory drugs (NSAIDs) and nonopioids for acute renal colic. Cochrane Database Syst Rev 2015(6):CD006027. [Accessed 19 July 2017].
  32. Turk C, Petrik A, Sarica K, et al. EAU guidelines on diagnosis and conservative management of urolithiasis. Eur Urol 2016;69(3):468–74. [Accessed 19 July 2017].
  33. Sin B, Koop K, Liu M, Yeh JY, Thandi P. Intravenous acetaminophen for renal colic in the emergency department: Where do we stand? Am J Ther 2017;24(1):e12–e19. [Accessed 19 July 2017].
  34. Campschroer T, Zhu Y, Duijvesz D, Grobbee DE, Lock MT. Alpha-blockers as medical expulsive therapy for ureteral stones. Cochrane Database Syst Rev 2014;4:CD008509. [Accessed 19 July 2017].
  35. Colli A, Conte D, Valle SD, Sciola V, Fraquelli M. Metaanalysis: Nonsteroidal anti-inflammatory drugs in biliary colic. Aliment Pharmacol Ther 2012;35(12):1370–78. [Accessed 19 July 2017].
  36. National Institute for Health and Clinical Excellence. Gallstone disease: Diagnosis and initial management. NICE guidelines CG188. London: NICE, 2014. Available at www. [Accessed 21 July 2017].
  37. Zakko SF. Uncomplicated gallstone disease in adults. UpToDate, 2016 uncomplicated-gallstone-disease-in-adults?topicKey=GAST %2F654&elapsedTimeMs=5&source=machineLearning&se archTerm=biliary+colic&selectedTitle=1%7E150&view=print &displayedView=full&anchor=H25 [Accessed 21 July 2017].
  38. Moore PA, Hersh EV. Combining ibuprofen and acetaminophen for acute pain management after thirdmolar extractions: Translating clinical research to dental practice. J Am Dent Assoc 2013;144(8):898–908. [Accessed 21 July 2017].
  39. Marjoribanks J, Proctor M, Farquhar C, Derks RS. [Accessed 21 July 2017].
  40. Nonsteroidal anti-inflammatory drugs for dysmenorrhoea. Cochrane Database Syst Rev 2010(1):CD001751. [Accessed 21 July 2017].
  41. Cunningham A, Breuer J, Dwyer D, et al. The prevention and management of herpes zoster. Med J Aust 2008;188(3):171–76. [Accessed 21 July 2017].
  42. Dworkin RH, Johnson RW, Breuer J, et al. [Accessed 21 July 2017].
  43. Recommendations for the management of herpes zoster. Clin Infect Dis 2007;44(Suppl 1):S1–26. [Accessed 21 July 2017].
  44. Dwyer DE, Cunningham AL. 10: Herpes simplex and varicella-zoster virus infections. Med J Aust 2002;177(5):267–73. [Accessed 21 July 2017].
  45. Berry JD, Petersen KL. A single dose of gabapentin reduces acute pain and allodynia in patients with herpes zoster. Neurology 2005;65(3):444–47. [Accessed 21 July 2017].
  46. Jensen-Dahm C, Rowbotham MC, Reda H, Petersen KL. [Accessed 21 July 2017].
  47. Effect of a single dose of pregabalin on herpes zoster pain. Trials 2011;12:55. [Accessed 21 July 2017].
  48. Lin PL, Fan SZ, Huang CH, et al. Analgesic effect of lidocaine patch 5% in the treatment of acute herpes zoster: A double-blind and vehicle-controlled study. Reg Anesth Pain Med 2008;33(4):320–25. [Accessed 21 July 2017].
  49. Chen N, Li Q, Yang J, Zhou M, Zhou D, He L. Antiviral treatment for preventing postherpetic neuralgia. Cochrane Database Syst Rev 2014(2):CD006866. [Accessed 21 July 2017].
  50. Chen N, Yang M, He L, Zhang D, Zhou M, Zhu C. [Accessed 21 July 2017].
  51. Corticosteroids for preventing postherpetic neuralgia. Cochrane Database Syst Rev 2010(12):CD005582. [Accessed 21 July 2017].
  52. Saarto T, Wiffen PJ. Antidepressants for neuropathic pain: A Cochrane review. J Neurol Neurosurg Psychiatry 2010;81(12):1372–73. [Accessed 21 July 2017].
  53. Moore RA, Derry S, Wiffen PJ, Straube S, Bendtsen L. Evidence for efficacy of acute treatment of episodic tensiontype headache: Methodological critique of randomised trials for oral treatments. Pain 2014;155(11):2220–28. [Accessed 21 July 2017].
  54. Chaibi A, Russell MB. Manual therapies for cervicogenic headache: A systematic review. J Headache Pain 2012;13(5):351–59. [Accessed 21 July 2017].
  55. Luedtke K, Allers A, Schulte LH, May A. Efficacy of interventions used by physiotherapists for patients with headache and migraine-systematic review and metaanalysis. Cephalalgia 2016;36(5):474–92. [Accessed 21 July 2017].
  56. Derry S, Moore RA. Paracetamol (acetaminophen) with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev 2013;4:CD008040. [Accessed 21 July 2017].
  57. Kirthi V, Derry S, Moore RA. Aspirin with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev 2013;4:CD008041. [Accessed 21 July 2017].
  58. Rabbie R, Derry S, Moore RA. Ibuprofen with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev 2013;4:CD008039. [Accessed 21 July 2017].
  59. Derry S, Rabbie R, Moore RA. Diclofenac with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev 2013;4:CD008783. [Accessed 21 July 2017].
  60. Colman I, Brown MD, Innes GD, Grafstein E, Roberts TE, Rowe BH. Parenteral metoclopramide for acute migraine: Meta-analysis of randomised controlled trials. BMJ 2004;329(7479):1369–73. [Accessed 21 July 2017].
  61. Friedman BW, Esses D, Solorzano C, et al. A randomized controlled trial of prochlorperazine versus metoclopramide for treatment of acute migraine. Ann Emerg Med 2008;52(4):399–406. [Accessed 21 July 2017].
  62. Coppola M, Yealy DM, Leibold RA. Randomized, placebo-controlled evaluation of prochlorperazine versus metoclopramide for emergency department treatment of migraine headache. Ann Emerg Med 1995;26(5):541–46. [Accessed 21 July 2017].
  63. Taggart E, Doran S, Kokotillo A, Campbell S, Villa-Roel C, Rowe BH. Ketorolac in the treatment of acute migraine: A systematic review. Headache 2013;53(2):277–87. [Accessed 21 July 2017].
  64. Thorlund K, Mills EJ, Wu P, et al. Comparative efficacy of triptans for the abortive treatment of migraine: A multiple treatment comparison meta-analysis. Cephalalgia 2014;34(4):258-67. [Accessed 21 July 2017].
  65. Tepper SJ. Opioids should not be used in migraine. Headache 2012;52(Suppl 1):30–34. [Accessed 21 July 2017].
  66. Buse DC, Pearlman SH, Reed ML, Serrano D, Ng-Mak DS, Lipton RB. Opioid use and dependence among persons with migraine: Results of the AMPP study. Headache 2012;52(1):18–36. [Accessed 21 July 2017].
  67. Finocchi C, Viani E. Opioids can be useful in the treatment of headache. Neurol Sci 2013;34(Suppl 1):S119–24. [Accessed 21 July 2017].
  68. Broner SW, Sun-Edelstein C, Lay CL. Cluster headache in women. Curr Pain Headache Rep 2007;11(2):127–30. [Accessed 21 July 2017].
  69. Finkel AG. Epidemiology of cluster headache. Curr Pain Headache Rep 2003;7(2):144–49. [Accessed 21 July 2017].
  70. Fischera M, Marziniak M, Gralow I, Evers S. The incidence and prevalence of cluster headache: A meta-analysis of population-based studies. Cephalalgia 2008;28(6):614–18. [Accessed 21 July 2017].
  71. Bennett MH, French C, Schnabel A, Wasiak J, Kranke P. Normobaric and hyperbaric oxygen therapy for migraine and cluster headache. Cochrane Database Syst Rev 2008(3):CD005219. [Accessed 21 July 2017].
  72. Cohen AS, Burns B, Goadsby PJ. High-flow oxygen for treatment of cluster headache: A randomized trial. JAMA 2009;302(22):2451–57. [Accessed 21 July 2017].
  73. Robbins MS, Starling AJ, Pringsheim TM, Becker WJ, [Accessed 21 July 2017].
  74. Schwedt TJ. Treatment of cluster headache: American Headache Society evidence-based guidelines. Headache 2016;56(7):1093–106. [Accessed 21 July 2017].
  75. Bennett MH, French C, Schnabel A, Wasiak J, Kranke P, Weibel S. Normobaric and hyperbaric oxygen therapy for the treatment and prevention of migraine and cluster headache. Cochrane Database Syst Rev 2015(12):CD005219. [Accessed 21 July 2017].
  76. Law S, Derry S, Moore RA. Triptans for acute cluster headache. Cochrane Database Syst Rev 2013;7:CD008042. [Accessed 21 July 2017].
  77. Francis GJ, Becker WJ, Pringsheim TM. Acute and preventive pharmacologic treatment of cluster headache. Neurology 2010;75(5):463–73. [Accessed 21 July 2017].
  78. van der Meer HA, Speksnijder CM, Engelbert R, [Accessed 21 July 2017].
  79. Lobbezoo F, Nijhuis-van der Sanden MW, Visscher CM. The association between headaches and temporomandibular disorders is confounded by bruxism and somatic complaints. Clin J Pain 2016. doi: 10.1097/ AJP.0000000000000470. [Accessed 21 July 2017].
  80. Costa YM, Conti PC, de Faria FA, Bonjardim LR. [Accessed 21 July 2017].
  81. Temporomandibular disorders and painful comorbidities: Clinical association and underlying mechanisms. Oral Surg Oral Med Oral Pathol Oral Radiol 2017;123(3):288–97. [Accessed 21 July 2017].
  82. Schiffman E, Ohrbach R, List T, et al. Diagnostic criteria for headache attributed to temporomandibular disorders. Cephalalgia 2012;32(9):683–92. [Accessed 21 July 2017].
  83. Mujakperuo HR, Watson M, Morrison R, Macfarlane TV. [Accessed 21 July 2017].
  84. Pharmacological interventions for pain in patients with temporomandibular disorders. Cochrane Database Syst Rev 2010(10):CD004715. [Accessed 21 July 2017].
  85. Ta LE, Dionne RA. Treatment of painful temporomandibular joints with a cyclooxygenase-2 inhibitor: A randomized placebo-controlled comparison of celecoxib to naproxen. Pain 2004;111(1-2):13–21. [Accessed 21 July 2017].
  86. Kelley JM, Kraft-Todd G, Schapira L, Kossowsky J, Riess H. The influence of the patient-clinician relationship on healthcare outcomes: A systematic review and metaanalysis of randomized controlled trials. PLoS One 2014;9(4):e94207. [Accessed 21 July 2017].
  87. National Opioid Use Guideline Group. Canadian guideline for safe and effective use of opioids for chronic non-cancer pain. Part B: Recommendations for practice. Ontario: [Accessed 21 July 2017].
  88. NOUGG, 2010. Available at http://nationalpaincentre. [Accessed 21 July 2017].
  89. Klinger R, Colloca L, Bingel U, Flor H. Placebo analgesia: Clinical applications. Pain 2014;155(6):1055–58. [Accessed 21 July 2017].
  90. Miller FG, Kaptchuk TJ. The power of context: Reconceptualizing the placebo effect. J R Soc Med 2008;101(5):222–25. [Accessed 21 July 2017].
  91. Lee C, Crawford C, Swann S, Active Self-Care Therapies for Pain Working Group. Multimodal, integrative therapies for the self-management of chronic pain symptoms. Pain Med 2014;15(Suppl 1):S76–85. [Accessed 21 July 2017].
  92. Hayden JA, van Tulder MW, Malmivaara A, Koes BW. Exercise therapy for treatment of non-specific low back pain. Cochrane Database Syst Rev 2005(3):CD000335. [Accessed 21 July 2017].
  93. Fransen M, McConnell S, Harmer AR, Van der Esch M, Simic M, Bennell KL. Exercise for osteoarthritis of the knee: A Cochrane systematic review. Br J Sports Med 2015;49(24):1554–57. [Accessed 21 July 2017].
  94. Fransen M, McConnell S, Hernandez-Molina G, [Accessed 21 July 2017].
  95. Reichenbach S. Exercise for osteoarthritis of the hip. Cochrane Database Syst Rev 2014;4:CD007912. [Accessed 21 July 2017].
  96. Busch AJ, Barber KA, Overend TJ, Peloso PM, Schachter CL. Exercise for treating fibromyalgia syndrome. Cochrane Database Syst Rev 2007(4):CD003786. [Accessed 21 July 2017].
  97. Scottish Intercollegiate Guidelines Network. Management of chronic pain (SIGN 136). Edinburgh: SIGN, 2013 [Accessed 1 September 2017].
  98. Williams AC, Eccleston C, Morley S. Psychological therapies for the management of chronic pain (excluding headache) in adults. Cochrane Database Syst Rev 2012;11:CD007407. [Accessed 1 September 2017].
  99. Eccleston C, Hearn L, Williams AC. Psychological therapies for the management of chronic neuropathic pain in adults. Cochrane Database Syst Rev 2015;10:CD011259. [Accessed 1 September 2017].
  100. Hooten W, Timming R, Belgrade M, et al. Assessment and management of chronic pain. Bloomington, MN: Institute for Clinical Systems Improvement, 2013 c26a36d83686607ad89ee835daa3c9db3f4c.pdf [Accessed 1 September 2017].
  101. Kahan M, Mailis-Gagnon A, Wilson L, Srivastava A, National [Accessed 1 September 2017].
  102. Opioid Use Guideline Group. Canadian guideline for safe and effective use of opioids for chronic noncancer pain: Clinical summary for family physicians. Part 1: General population. Can Fam Physician 2011;57(11):1257–66, e407-18. [Accessed 1 September 2017].
  103. The Royal Australasian College of Physicians. Prescription opioid policy: Improving management of chronic nonmalignant pain and prevention of problems associated with prescription opioid use. Sydney: RACP, 2009. [Accessed 1 September 2017].
  104. Manchikanti L, Abdi S, Atluri S, et al. American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic non-cancer pain: Part 2: Guidance. Pain Physician 2012;15(3 Suppl):S67–116. [Accessed 1 September 2017].
  105. National Center for Injury Prevention and Control. Common elements in guidelines for prescribing opioids for chronic pain. NCIPC, 2014 drugoverdose/pdf/common_elements_in_guidelines_for_ prescribing_opioids-a.pdf [Accessed 21 July 2017].
  106. Moulin D, Boulanger A, Clark AJ, et al. Pharmacological management of chronic neuropathic pain: Revised consensus statement from the Canadian Pain Society. Pain Res Manag 2014;19(6):328–35. [Accessed 21 July 2017].
  107. Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for medical use: A systematic review and meta-analysis. JAMA. 2015;313(24):2456-73. [Accessed 21 July 2017].
  108. Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for neuropathic pain in adults: A systematic review and meta-analysis. Lancet Neurol 2015;14(2):162–73. [Accessed 21 July 2017].
  109. Australian and New Zealand College of Anaesthetists. Statement on ‘medicinal cannabis’ with particular reference to its use in the management of patients with chronic noncancer pain (PM10). Melbourne: ANZCA, 2015 [Accessed 21 July 2017].
  110. Stacey BR, Barrett JA, Whalen E, Phillips KF, Rowbotham MC. Pregabalin for postherpetic neuralgia: Placebocontrolled trial of fixed and flexible dosing regimens on allodynia and time to onset of pain relief. J Pain 2008;9(11):1006–17. [Accessed 21 July 2017].
  111. Wang F, Ruberg SJ, Gaynor PJ, Heinloth AN, Arnold LM. Early improvement in pain predicts pain response at endpoint in patients with fibromyalgia. J Pain 2011;12(10):1088–94. [Accessed 21 July 2017].
  112. Therapeutics Initiative. Benefits and harms of drugs for ‘neuropathic’ pain. Vancouver: University of British Columbia, 2015 [Accessed 21 July 2017].
  113. Hughes MA, Biggs JJ, Theise MS, Graziano K, Robbins RB, Effiong AC. Recommended opioid prescribing practices for use in chronic non-malignant pain: A systematic review of treatment guidelines. J Manag Care Med 2011;14(3):52. [Accessed 21 July 2017].
  114. National Opioid Use Guideline Group. Canadian guideline for safe and effective use of opioids for chronic non-cancer pain. Ontario: NOUGG, 2010. Available at http://nationalpaincentre. [Accessed 21 July 2017].
  115. Deyo RA, Von Korff M, Duhrkoop D. Opioids for low back pain. BMJ 2015;350:g6380. [Accessed 21 July 2017].
  116. Chou R, Fanciullo GJ, Fine PG, et al. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain 2009;10(2):113–30. [Accessed 21 July 2017].
  117. Fagan MJ, Chen JT, Diaz JA, Reinert SE, Stein MD. Do internal medicine residents find pain medication agreements useful? Clin J Pain 2008;24(1):35–38. [Accessed 21 July 2017].
  118. Bazazi AR, Zaller ND, Fu JJ, Rich JD. Preventing opiate overdose deaths: Examining objections to takehome naloxone. J Health Care Poor Underserved 2010;21(4):1108–13. [Accessed 21 July 2017].
  119. McDonald R, Strang J. Are take-home naloxone programmes effective? Systematic review utilizing application of the Bradford Hill criteria. Addiction 2016;111(7):1177–87. [Accessed 21 July 2017].
  120. Strang J, McDonald R, Alqurshi A, Royall P, Taylor D, Forbes B. Naloxone without the needle – Systematic review of candidate routes for non-injectable naloxone for opioid overdose reversal. Drug Alcohol Depend 2016;163:16–23. [Accessed 21 July 2017].
  121. Krebs EE, Lorenz KA, Bair MJ, et al. Development and initial validation of the PEG, a three-item scale assessing pain intensity and interference. J Gen Intern Med 2009;24(6):733–38. [Accessed 21 July 2017].
  122. Boudreau D, Von Korff M, Rutter CM, et al. Trends in long-term opioid therapy for chronic non-cancer pain. Pharmacoepidemiol Drug Saf 2009;18(12):1166–75. [Accessed 21 July 2017].
  123. Smith HS, Peppin JF. Toward a systematic approach to opioid rotation. J Pain Res 2014;7:589–608. [Accessed 21 July 2017].
  124. The British Pain Society. Opioids for persistent pain: Good practice. London: The British Pain Society, 2010. [Accessed 21 July 2017].
  125. Becker WC, Fraenkel L, Edelman EJ, et al. Instruments to assess patient-reported safety, efficacy, or misuse of current opioid therapy for chronic pain: A systematic review. Pain 2013;154(6):905–16. [Accessed 21 July 2017].
  126. Gourlay DL, Heit HA, Almahrezi A. Universal precautions in pain medicine: A rational approach to the treatment of chronic pain. Pain Med 2005;6(2):107–12. [Accessed 21 July 2017].
  127. Jammal W, Gown G. Opioid prescribing pitfalls: Medicolegal and regulatory issues. Aust Prescr 2015;38:198–203. [Accessed 21 July 2017].
  128. Noble M, Treadwell JR, Tregear SJ, et al. Long-term opioid management for chronic noncancer pain. Cochrane Database Syst Rev 2010(1):CD006605. [Accessed 21 July 2017].
  129. Häuser W, Bock F, Engeser P, Tölle T, Willweber-Strumpf A, Petzke F. Long-term opioid use in non-cancer pain. Dtsch Ärztebl Int 2014;111(43):732–40. [Accessed 21 July 2017].
  130. Tawfic Q, Kumar K, Pirani Z, Armstrong K. Prevention of chronic post-surgical pain: The importance of early identification of risk factors. J Anesth 2017;31(3):424–31. [Accessed 21 July 2017].
  131. Wylde V, Hewlett S, Learmonth ID, Dieppe P. Persistent pain after joint replacement: Prevalence, sensory qualities, and postoperative determinants. Pain 2011;152(3):566–72. [Accessed 21 July 2017].
  132. Chan MT, Wan AC, Gin T, Leslie K, Myles PS. Chronic postsurgical pain after nitrous oxide anesthesia. Pain 2011;152(11):2514–20. [Accessed 21 July 2017].
  133. Macrae WA. Chronic post-surgical pain: 10 years on. Br J Anaesth 2008;101(1):77–86. [Accessed 21 July 2017].
  134. Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: Risk factors and prevention. Lancet 2006;367(9522):1618–25. [Accessed 21 July 2017].
  135. Treede RD, Rief W, Barke A, et al. A classification of chronic pain for ICD-11. Pain 2015;156(6):1003–7. [Accessed 21 July 2017].
  136. Theunissen M, Peters ML, Bruce J, Gramke HF, Marcus MA. Preoperative anxiety and catastrophizing: A systematic review and meta-analysis of the association with chronic postsurgical pain. Clin J Pain 2012;28(9):819–41. [Accessed 21 July 2017].
  137. Hinrichs-Rocker A, Schulz K, Jarvinen I, Lefering R, Simanski C, Neugebauer EA. Psychosocial predictors and correlates for chronic post-surgical pain (CPSP) – A systematic review. Eur J Pain 2009;13(7):719–30. [Accessed 21 July 2017].
  138. Buchheit T, Van de Ven T, Shaw A. Epigenetics and the transition from acute to chronic pain. Pain Med 2012;13(11):1474–90. [Accessed 21 July 2017].
  139. Mauck M, Van de Ven T, Shaw AD. Epigenetics of chronic pain after thoracic surgery. Curr Opin Anaesthesiol 2014;27(1):1–5. [Accessed 21 July 2017].
  140. Wesselmann U, Baranowski AP, Borjesson M, et al. [Accessed 21 July 2017].
  141. Emerging therapies and novel approaches to visceral pain. Drug Discov Today Ther Strateg 2009;6(3):89–95. [Accessed 21 July 2017].
  142. Olesen AE, Farmer AD, Olesen SS, Aziz Q, Drewes AM. Management of chronic visceral pain. Pain Manag 2016;6(5):469–86. [Accessed 21 July 2017].
  143. Queiroz LP. Worldwide epidemiology of fibromyalgia. Curr Pain Headache Rep 2013;17(8):356. [Accessed 21 July 2017].
  144. Hauser W, Zimmer C, Felde E, Kollner V. What are the key symptoms of fibromyalgia? Results of a survey of the German Fibromyalgia Association. Schmerz 2008;22(2):176–83. [Accessed 21 July 2017].
  145. Clauw DJ, Arnold LM, McCarberg BH, FibroCollaborative. The science of fibromyalgia. Mayo Clin Proc 2011;86(9):907–11. [Accessed 21 July 2017].
  146. Macfarlane GJ, Kronisch C, Dean LE, et al. EULAR revised recommendations for the management of fibromyalgia. Ann Rheum Dis 2017;76(2):318–28. [Accessed 21 July 2017].
  147. Angel Garcia D, Martinez Nicolas I, Saturno Hernandez PJ. Clinical approach to fibromyalgia: Synthesis of evidencebased recommendations, a systematic review. Reumatol Clin 2016;12(2):65–71. [Accessed 21 July 2017].
  148. Clauw DJ. Fibromyalgia: A clinical review. JAMA 2014;311(15):1547–55. [Accessed 21 July 2017].
  149. Fitzcharles MA, Ste-Marie PA, Goldenberg DL, et al. 2012 Canadian guidelines for the diagnosis and management of fibromyalgia syndrome: Executive summary. Pain Res Manag 2013;18(3):119–26. [Accessed 21 July 2017].
  150. Hauser W, Thieme K, Turk DC. Guidelines on the management of fibromyalgia syndrome – A systematic review. Eur J Pain 2010;14(1):5–10. [Accessed 21 July 2017].
  151. Goebel A, Barker C, Turner-Stokes L, et al. Complex regional pain syndrome in adults: UK guidelines for diagnosis, referral and management in primary and secondary care. London: RCP, 2012. [Accessed 21 July 2017].
  152. Casale R, Atzeni F, Sarzi-Puttini P. The therapeutic approach to complex regional pain syndrome: Light and shade. Clin Exp Rheumatol 2015;33(1 Suppl 88):S126–39. [Accessed 21 July 2017].
  153. Birklein F, O’Neill D, Schlereth T. Complex regional pain syndrome: An optimistic perspective. Neurology 2015;84(1):89–96. [Accessed 21 July 2017].
  154. Borchers AT, Gershwin ME. Complex regional pain syndrome: A comprehensive and critical review. Autoimmun Rev 2014;13(3):242–65. [Accessed 21 July 2017].
  155. Lohnberg JA, Altmaier EM. A review of psychosocial factors in complex regional pain syndrome. J Clin Psychol Med Settings 2013;20(2):247–54. [Accessed 21 July 2017].
  156. Cossins L, Okell RW, Cameron H, Simpson B, Poole HM, Goebel A. Treatment of complex regional pain syndrome in adults: A systematic review of randomized controlled trials published from June 2000 to February 2012. Eur J Pain 2013;17(2):158–73. [Accessed 21 July 2017].
  157. Goh EL, Chidambaram S, Ma D. Complex regional pain syndrome: A recent update. Burns Trauma 2017;5:2. [Accessed 21 July 2017].
  158. Larochelle MR, Liebschutz JM, Zhang F, Ross-Degnan D, Wharam JF. Opioid prescribing after nonfatal overdose and association with repeated overdose: A cohort study. Ann Intern Med 2016;164(1):1–9. [Accessed 21 July 2017].
  159. Zanini C, Sarzi-Puttini P, Atzeni F, Di Franco M, Rubinelli S. Building bridges between doctors and patients: The design and pilot evaluation of a training session in argumentation for chronic pain experts. BMC Med Educ 2015;15:89. [Accessed 21 July 2017].
  160. Gammaitoni AR, Fine P, Alvarez N, McPherson ML, Bergmark S. Clinical application of opioid equianalgesic data. Clin J Pain 2003;19(5):286–97. [Accessed 21 July 2017].
  161. NSW Therapeutic Advisory Group Inc. Preventing and managing problems with opioid prescribing for chronic noncancer pain. Sydney: NSW TAG, 2015. Available at www. practical-guidance/pain-guidance-july-2015.pdf [Accessed 26 July 2017].
  162. Busse JW, Craigie S, Juurlink DN, et al. Guideline for opioid therapy and chronic noncancer pain. CMAJ 2017;189(18):E659–E66. [Accessed 26 July 2017].
  163. Windmill J, Fisher E, Eccleston C, et al. Interventions for the reduction of prescribed opioid use in chronic non-cancer pain. Cochrane Database Syst Rev 2013(9):CD010323. [Accessed 26 July 2017].
  164. Nilsen HK, Stiles TC, Landro NI, Fors EA, Kaasa S, Borchgrevink PC. Patients with problematic opioid use can be weaned from codeine without pain escalation. Acta Anaesthesiol Scand 2010;54(5):571–79. [Accessed 26 July 2017].
  165. Baron MJ, McDonald PW. Significant pain reduction in chronic pain patients after detoxification from high-dose opioids. J Opioid Manag 2006;2(5):277–82. [Accessed 26 July 2017].
  166. Crisostomo RA, Schmidt JE, Hooten WM, Kerkvliet JL, Townsend CO, Bruce BK. Withdrawal of analgesic medication for chronic low-back pain patients: Improvement in outcomes of multidisciplinary rehabilitation regardless of surgical history. Am J Phys Med Rehabil 2008;87(7):527–36. [Accessed 26 July 2017].
  167. Younger J, Barelka P, Carroll I, et al. Reduced cold pain tolerance in chronic pain patients following opioid detoxification. Pain Med 2008;9(8):1158–63. [Accessed 26 July 2017].
  168. Hooten WM, Mantilla CB, Sandroni P, Townsend CO. Associations between heat pain perception and opioid dose among patients with chronic pain undergoing opioid tapering. Pain Med 2010;11(11):1587–98. [Accessed 26 July 2017].
  169. Wang H, Akbar M, Weinsheimer N, Gantz S, Schiltenwolf M. Longitudinal observation of changes in pain sensitivity during opioid tapering in patients with chronic low-back pain. Pain Med 2011;12(12):1720–26. [Accessed 26 July 2017].
  170. Berna C, Kulich RJ, Rathmell JP. Tapering long-term opioid therapy in chronic noncancer pain: Evidence and recommendations for everyday practice. Mayo Clin Proc 2015;90(6):828–42. [Accessed 26 July 2017].
  171. International Association for the Study of Pain. Classification of chronic pain. 2nd edn. Washington DC: IASP, 2011 aspx?ItemNumber=1673 [Accessed 26 July 2017].
  172. Katz J, Weinrib A, Fashler SR, et al. The Toronto General Hospital Transitional Pain Service: Development and implementation of a multidisciplinary program to prevent chronic postsurgical pain. J Pain Res 2015;8:695–702. [Accessed 26 July 2017].
  173. Denk F, McMahon SB, Tracey I. Pain vulnerability: A neurobiological perspective. Nat Neurosci 2014;17(2):192– 200. [Accessed 26 July 2017].
  174. Eisenberger NI. The neural bases of social pain: Evidence for shared representations with physical pain. Psychosom Med 2012;74(2):126–35. [Accessed 26 July 2017].
  175. Kosek E, Cohen M, Baron R, et al. Do we need a third mechanistic descriptor for chronic pain states? Pain 2016;157:1382–86. [Accessed 26 July 2017].
  176. Merskey H, Bogduk N. International Association for the Study of Pain Task Force on Taxonomy. Classification of chronic pain: Descriptions of chronic pain syndromes and definitions of pain terms. 2nd edn. Seattle: IASP Press, 1994; p. 222. [Accessed 26 July 2017].
  177. Smart KM, Blake C, Staines A, Thacker M, Doody C. Mechanisms-based classifications of musculoskeletal pain: Part 3 of 3: Symptoms and signs of nociceptive pain in patients with low back (+/– leg) pain. Man Ther 2012;17(4):352–57. [Accessed 26 July 2017].
  178. Costigan M, Scholz J, Woolf CJ. Neuropathic pain: A maladaptive response of the nervous system to damage. Annu Rev Neurosci 2009;32:1–32. [Accessed 26 July 2017].
  179. Freynhagen R, Baron R, Gockel U, Tolle TR. painDETECT: A new screening questionnaire to identify neuropathic components in patients with back pain. Curr Med Res Opin 2006;22(10):1911–20. [Accessed 26 July 2017].
  180. O’Connor AB, Dworkin RH. Treatment of neuropathic pain: An overview of recent guidelines. Am J Med 2009;122(10 Suppl):S22–32. [Accessed 26 July 2017].
  181. Arendt-Nielsen L, Nie H, Laursen MB, et al. Sensitization in patients with painful knee osteoarthritis. Pain 2010; 149(3):573–81. [Accessed 26 July 2017].
  182. Kosek E, Ordeberg G. Lack of pressure pain modulation by heterotopic noxious conditioning stimulation in patients with painful osteoarthritis before, but not following, surgical pain relief. Pain 2000;88(1):69–78. [Accessed 26 July 2017].
  183. Aranda-Villalobos P, Fernandez-de-Las-Penas C, NavarroEspigares JL, et al. Normalization of widespread pressure pain hypersensitivity after total hip replacement in patients with hip osteoarthritis is associated with clinical and functional improvements. Arthritis Rheum 2013;65(5):1262–70. [Accessed 26 July 2017].
  184. Graven-Nielsen T, Wodehouse T, Langford RM, ArendtNielsen L, Kidd BL. Normalization of widespread hyperesthesia and facilitated spatial summation of deep-tissue pain in knee osteoarthritis patients after knee replacement. Arthritis Rheum 2012;64(9):2907–16. [Accessed 26 July 2017].
  185. Kosek E, Ordeberg G. Abnormalities of somatosensory perception in patients with painful osteoarthritis normalize following successful treatment. Eur J Pain 2000;4(3):229–38. [Accessed 26 July 2017].
  186. Rosenquist EWK. Evaluation of chronic pain in adults. UpToDate 2016 evaluation-of-chronic-pain-in-adults?source=search_ result&search=pain%20assessment&selectedTitle=1~150 - H15544430 [Accessed 3 March 2017].
  187. Kirsh KL, Jass C, Bennett DS, Hagen JE, Passik SD. Initial development of a survey tool to detect issues of chemical coping in chronic pain patients. Palliat Support Care 2007;5(3):219–26. [Accessed 3 March 2017].
  188. Flor H. Psychological pain interventions and neurophysiology: Implications for a mechanism-based approach. Am Psychol 2014;69(2):188–96. [Accessed 3 March 2017].
  189. Nicholas MK, Linton SJ, Watson PJ, Main CJ, Decade of the Flags Working Group. Early identification and management of psychological risk factors (‘yellow flags’) in patients with low back pain: A reappraisal. Phys Ther 2011;91(5):737–53. [Accessed 3 March 2017].
  190. Ip HY, Abrishami A, Peng PW, Wong J, Chung F. Predictors of postoperative pain and analgesic consumption: A qualitative systematic review. Anesthesiology 2009;111(3):657–77. [Accessed 3 March 2017].
  191. Leeuw M, Goossens ME, Linton SJ, Crombez G, Boersma K, Vlaeyen JW. The fear-avoidance model of musculoskeletal pain: Current state of scientific evidence. J Behav Med 2007;30(1):77–94. [Accessed 3 March 2017].
  192. Hjermstad MJ, Fayers PM, Haugen DF, et al. Studies comparing numerical rating scales, verbal rating scales, and visual analogue scales for assessment of pain intensity in adults: A systematic literature review. J Pain Symptom Manage 2011;41(6):1073–93. [Accessed 3 March 2017].
  193. Chen L, Vo T, Seefeld L, et al. Lack of correlation between opioid dose adjustment and pain score change in a group of chronic pain patients. J Pain 2013;14(4):384–92. [Accessed 3 March 2017].
  194. Chou R, Turner JA, Devine EB, et al. The effectiveness and risks of long-term opioid therapy for chronic pain: A systematic review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med 2015;162(4):276–86. [Accessed 3 March 2017].
  195. Sehgal N, Manchikanti L, Smith HS. Prescription opioid abuse in chronic pain: A review of opioid abuse predictors and strategies to curb opioid abuse. Pain Physician 2012;15(3 Suppl):ES67–92. [Accessed 3 March 2017].
  196. Gordon A, Cone EJ, DePriest AZ, Axford-Gatley RA, Passik SD. Prescribing opioids for chronic noncancer pain in primary care: Risk assessment. Postgrad Med 2014;126(5):159–66. [Accessed 3 March 2017].
  197. Di Blasi Z, Harkness E, Ernst E, Georgiou A, Kleijnen J. Influence of context effects on health outcomes: [Accessed 3 March 2017].
  198. A systematic review. Lancet 2001;357(9258):757–62. [Accessed 3 March 2017].
  199. Cohen ML. Placebo theory. In: Hutson M, Ward A, editors. [Accessed 3 March 2017].
  200. Oxford textbook of musculoskeletal medicine. 2nd edn. Oxford: Oxford University Press, 2016; p. 200–06. [Accessed 3 March 2017].
  201. Manchikanti L, Giordano J, Fellows B, Hirsch JA. Placebo and nocebo in interventional pain management: A friend or a foe – or simply foes? Pain Physician 2011;14(2):E157–75. [Accessed 3 March 2017].
  202. Benedetti F, Amanzio M. The neurobiology of placebo analgesia: From endogenous opioids to cholecystokinin. Prog Neurobiol 1997;52(2):109–25. [Accessed 3 March 2017].
  203. Finniss DG, Kaptchuk TJ, Miller F, Benedetti F. Biological, clinical, and ethical advances of placebo effects. Lancet 2010;375(9715):686–95. [Accessed 3 March 2017].
  204. Finniss DG, Benedetti F. The placebo response: Implications for neural blockade. In: Cousins M, Carr D, Horlocker T, Bridenbaugh P, editors. Cousins and Bridenbaugh’s neural blockade in clinical anaesthesia and pain medicine. Philadelphia: Lippincott Williams and Wilkins, 2009, p. 794–800. [Accessed 3 March 2017].
  205. Oeltjenbruns J, Schafer M. Clinical significance of the placebo effect. Anaesthesist 2008;57(5):447–63. [Accessed 3 March 2017].
  206. Hrobjartsson A, Gotzsche PC. Placebo interventions for all clinical conditions. Cochrane Database Syst Rev 2010(1):CD003974. [Accessed 3 March 2017].
  207. Vase L, Riley JL 3rd, Price DD. A comparison of placebo effects in clinical analgesic trials versus studies of placebo analgesia. Pain 2002;99(3):443–52. [Accessed 3 March 2017].
  208. Vase L, Petersen GL, Riley JL 3rd, Price DD. Factors contributing to large analgesic effects in placebo mechanism studies conducted between 2002 and 2007. Pain 2009;145(1–2):36–44. [Accessed 3 March 2017].
  209. Petersen GL, Finnerup NB, Colloca L, et al. The magnitude of nocebo effects in pain: A meta-analysis. Pain 2014;155(8):1426–34. [Accessed 3 March 2017].
  210. Peerdeman KJ, van Laarhoven AI, Keij SM, et al. Relieving patients’ pain with expectation interventions: A metaanalysis. Pain 2016;157(6):1179–91. [Accessed 3 March 2017].
  211. Levine JD, Gordon NC, Fields HL. The mechanism of placebo analgesia. Lancet 1978;2(8091):654–57. [Accessed 3 March 2017].
  212. Benedetti F, Amanzio M, Maggi G. Potentiation of placebo analgesia by proglumide. Lancet 1995;346(8984):1231. [Accessed 3 March 2017].
  213. Benedetti F, Amanzio M, Rosato R, Blanchard C. Nonopioid placebo analgesia is mediated by CB1 cannabinoid receptors. Nat Med 2011;17(10):1228–30. [Accessed 3 March 2017].
  214. Jarcho JM, Feier NA, Labus JS, et al. Placebo analgesia: Self-report measures and preliminary evidence of cortical dopamine release associated with placebo response. Neuroimage Clin 2016;10:107–14. [Accessed 3 March 2017].
  215. Brody H. The lie that heals: The ethics of giving placebos. Ann Intern Med 1982;97(1):112–18. [Accessed 3 March 2017].
  216. Wluka A, Chou L, Briggs A, Cicuttini F. Understanding the needs of consumers with musculoskeletal conditions: Consumers’ perceived needs of health information, health services and other non-medical services: A systematic scoping review. Melbourne: MOVE muscle, bone & joint health, 2016 Completed/Needs-of-Consumers/Consumer_Needs_Report_ Web.aspx [Accessed 26 July 2017].
  217. Crichton B, Green M. GP and patient perspectives on treatment with non-steroidal anti-inflammatory drugs for the treatment of pain in osteoarthritis. Curr Med Res Opin 2002;18(2):92–96. [Accessed 26 July 2017].
  218. McHugh G, Thoms G. Living with chronic pain: The patient’s perspective. Nurs Stand 2001;15(52):33–37. [Accessed 26 July 2017].
  219. Heiberg T, Kvien TK. Preferences for improved health examined in 1024 patients with rheumatoid arthritis: Pain has highest priority. Arthritis Rheum 2002;47(4):391–97. [Accessed 26 July 2017].
  220. O’Brien EM, Staud RM, Hassinger AD, et al. Patientcentered perspective on treatment outcomes in chronic pain. Pain Med 2010;11(1):6–15. [Accessed 26 July 2017].
  221. Toye F, Seers K, Allcock N, et al. Patients’ experiences of chronic non-malignant musculoskeletal pain: A qualitative systematic review. Br J Gen Pract 2013;63(617):e829–41. [Accessed 26 July 2017].
  222. Zanini C, Sarzi-Puttini P, Atzeni F, Di Franco M, Rubinelli S. Doctors’ insights into the patient perspective: A qualitative study in the field of chronic pain. Biomed Res Int 2014;2014:514230. [Accessed 26 July 2017].
  223. Fu Y, McNichol E, Marczewski K, Closs SJ. Patientprofessional partnerships and chronic back pain selfmanagement: A qualitative systematic review and synthesis. Health Soc Care Community 2016;24(3):247–59. [Accessed 26 July 2017].
  224. Coulter A, Collins A. Making shared decision-making a reality: No decision about me, without me. London: The King’s Fund; 2011. [Accessed 26 July 2017].
  225. O’Shea E. Communicating risk to patients. ICGP Quality in Practice Committee, 2014. [Accessed 26 July 2017].
  226. Hoffmann TC, Montori VM, Del Mar C. The connection between evidence-based medicine and shared decision making. JAMA 2014;312(13):1295–96. [Accessed 26 July 2017].
  227. Stacey D, Bennett CL, Barry MJ, et al. Decision aids for people facing health treatment or screening decisions. Cochrane Database Syst Rev 2011(10):CD001431. [Accessed 26 July 2017].
  228. Hoffmann TC, Legare F, Simmons MB, et al. Shared decision making: What do clinicians need to know and why should they bother? Med J Aust 2014;201(1):35–39. [Accessed 26 July 2017].
  229. Ahmed H, Naik G, Willoughby H, Edwards AG. Communicating risk. BMJ 2012;344:e3996. [Accessed 26 July 2017].
  230. Chewning B, Bylund CL, Shah B, Arora NK, Gueguen JA, Makoul G. Patient preferences for shared decisions: A systematic review. Patient Educ Couns 2012;86(1):9–18. [Accessed 26 July 2017].
  231. Cepeda MS, Africano JM, Polo R, Alcala R, Carr DB. What decline in pain intensity is meaningful to patients with acute pain? Pain 2003;105(1–2):151–57. [Accessed 26 July 2017].
  232. Jensen MP, Chen C, Brugger AM. Interpretation of visual analog scale ratings and change scores: A reanalysis of two clinical trials of postoperative pain. J Pain 2003;4(7):407–14. [Accessed 26 July 2017].
  233. Lee JS, Hobden E, Stiell IG, Wells GA. Clinically important change in the visual analog scale after adequate pain control. Acad Emerg Med 2003;10(10):1128–30. [Accessed 26 July 2017].
  234. Farrar JT, Portenoy RK, Berlin JA, Kinman JL, Strom BL. Defining the clinically important difference in pain outcome measures. Pain 2000;88(3):287–94. [Accessed 26 July 2017].
  235. Farrar JT, Young JP Jr, LaMoreaux L, Werth JL, Poole RM. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain 2001;94(2):149–58. [Accessed 26 July 2017].
  236. Moore A, Derry S, Eccleston C, Kalso E. Expect analgesic failure; pursue analgesic success. BMJ 2013;346:f2690. [Accessed 26 July 2017].
  237. Kamper SJ, Apeldoorn AT, Chiarotto A, et al. Multidisciplinary biopsychosocial rehabilitation for chronic low back pain: Cochrane systematic review and metaanalysis. BMJ 2015;350:h444. [Accessed 26 July 2017].
  238. Crowe M, Jordan J, Burrell B, Jones V, Gillon D, Harris S. Mindfulness-based stress reduction for long-term physical conditions: A systematic review. Aust N Z J Psychiatry 2016;50(1):21–32. [Accessed 26 July 2017].
  239. Bawa FL, Mercer SW, Atherton RJ, et al. Does mindfulness improve outcomes in patients with chronic pain? Systematic review and meta-analysis. Br J Gen Pract 2015;65(635):e387–400. [Accessed 26 July 2017].
  240. Australasian Faculty of Occupational and Environmental Medicine. Australian consensus statement on the health benefits of work. RACP, 2015 [Accessed 26 July 2017].
  241. Veehof MM, Trompetter HR, Bohlmeijer ET, Schreurs KM. Acceptance- and mindfulness-based interventions for the treatment of chronic pain: A meta-analytic review. Cogn Behav Ther 2016;45(1):5–31. [Accessed 26 July 2017].
  242. Gallagher L, McAuley J, Moseley GL. A randomizedcontrolled trial of using a book of metaphors to reconceptualize pain and decrease catastrophizing in people with chronic pain. Clin J Pain 2013;29(1):20–25. [Accessed 26 July 2017].
  243. Clarke CL, Ryan CG, Martin DJ. Pain neurophysiology education for the management of individuals with chronic low back pain: Systematic review and meta-analysis. Man Ther 2011;16(6):544–49. [Accessed 26 July 2017].
  244. Louw A, Diener I, Butler DS, Puentedura EJ. The effect of neuroscience education on pain, disability, anxiety, and stress in chronic musculoskeletal pain. Arch Phys Med Rehabil 2011;92(12):2041–56. [Accessed 26 July 2017].
  245. Chou R, Deyo R, Friedly J, et al. Nonpharmacologic therapies for low back pain: A systematic review for an American College of Physicians clinical practice guideline. Ann Intern Med 2017;166(7):493–505. [Accessed 26 July 2017].
  246. Geneen LJ, Moore RA, Clarke C, Martin D, Colvin LA, Smith BH. Physical activity and exercise for chronic pain in adults: An overview of Cochrane reviews. Cochrane Database Syst Rev 2017;1:Cd011279. [Accessed 26 July 2017].
  247. Yamato TP, Maher CG, Saragiotto BT, et al. Pilates for low back pain. Cochrane Database Syst Rev 2015(7):Cd010265. [Accessed 26 July 2017].
  248. Australasian Faculty of Occupational and Environmental Medicine. Australian consensus statement on the health benefits of work RACP, 2015 [Accessed 26 July 2017].
  249. Australasian Faculty of Occupational and Evironmental Medicine. Helping people return to work: Using evidence for better outcomes. RACP, 2010. Available at www.workcover. people_return_to_work.pdf [Accessed 26 July 2017].
  250. Qaseem A, Wilt TJ, McLean RM, Forciea MA. Noninvasive treatments for acute, subacute, and chronic low back pain: A clinical practice guideline from the American College of Physicians. Ann Intern Med 2017;166(7):514–30. [Accessed 26 July 2017].
  251. Steffens D, Maher CG, Pereira LS, et al. Prevention of low back pain: A systematic review and meta-analysis. JAMA Intern Med 2016;176(2):199–208. [Accessed 26 July 2017].
  252. Page MJ, Green S, McBain B, et al. Manual therapy and exercise for rotator cuff disease. Cochrane Database Syst Rev 2016(6):Cd012224. [Accessed 26 July 2017].
  253. Oliveira CB, Franco MR, Maher CG, et al. Physical activity interventions for increasing objectively measured physical activity levels in patients with chronic musculoskeletal pain: A systematic review. Arthritis Care Res (Hoboken) 2016;68(12):1832–42. [Accessed 26 July 2017].
  254. O’Keeffe M, Purtill H, Kennedy N, et al. Comparative effectiveness of conservative interventions for nonspecific chronic spinal pain: Physical, behavioral/psychologically informed, or combined? A systematic review and metaanalysis. J Pain 2016;17(7):755–74. [Accessed 26 July 2017].
  255. Chaibi A, Russell MB. Manual therapies for primary chronic headaches: A systematic review of randomized controlled trials. J Headache Pain 2014;15:67. [Accessed 26 July 2017].
  256. Damgaard P, Bartels EM, Ris I, Christensen R, JuulKristensen B. Evidence of physiotherapy interventions for patients with chronic neck pain: A systematic review of randomised controlled trials. ISRN Pain 2013;2013:567175. [Accessed 26 July 2017].
  257. Ebadi S, Henschke N, Nakhostin Ansari N, Fallah E, van Tulder MW. Therapeutic ultrasound for chronic low-back pain. Cochrane Database Syst Rev 2014(3):Cd009169. [Accessed 26 July 2017].
  258. Geneen LJ, Martin DJ, Adams N, et al. Effects of education to facilitate knowledge about chronic pain for adults: A systematic review with meta-analysis. Syst Rev 2015;4:132. [Accessed 26 July 2017].
  259. Wong JJ, Cote P, Sutton DA, et al. Clinical practice guidelines for the noninvasive management of low back pain: A systematic review by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration. Eur J Pain 2017;21(2):201–16. [Accessed 26 July 2017].
  260. Moseley GL, Butler DS. Fifteen years of explaining pain: [Accessed 26 July 2017].
  261. The past, present, and future. J Pain 2015;16(9):807–13. [Accessed 26 July 2017].
  262. Louw A, Zimney K, Puentedura EJ, Diener I. The efficacy of pain neuroscience education on musculoskeletal pain: A systematic review of the literature. Physiother Theory Pract 2016;32(5):332–55. [Accessed 26 July 2017].
  263. Derry S, Wiffen PJ, Aldington D, Moore RA. Nortriptyline for neuropathic pain in adults. Cochrane Database Syst Rev 2015;1:CD011209. [Accessed 26 July 2017].
  264. 248. Moore RA, Derry S, Aldington D, Cole P, Wiffen PJ. Amitriptyline for neuropathic pain in adults. Cochrane Database Syst Rev 2015;7:CD008242. [Accessed 26 July 2017].
  265. Hauser W, Wolfe F, Tolle T, Uceyler N, Sommer C. The role of antidepressants in the management of fibromyalgia syndrome: A systematic review and meta-analysis. CNS Drugs 2012;26(4):297–307. [Accessed 26 July 2017].
  266. Van Oosterwijck J, Meeus M, Paul L, et al. Pain physiology education improves health status and endogenous pain inhibition in fibromyalgia: A double-blind randomized controlled trial. Clin J Pain 2013;29(10):873–82. [Accessed 26 July 2017].
  267. Friedman AJ, Cosby R, Boyko S, Hatton-Bauer J, Turnbull G. Effective teaching strategies and methods of delivery for patient education: A systematic review and practice guideline recommendations. J Cancer Educ 2011;26(1):12–21. [Accessed 26 July 2017].
  268. Derry CJ, Derry S, Moore RA. Caffeine as an analgesic adjuvant for acute pain in adults. Cochrane Database Syst Rev 2014;12:CD009281. [Accessed 26 July 2017].
  269. Haddad PM, Anderson IM. Recognising and managing antidepressant discontinuation symptoms. Adv Psychiatr Treat 2007;13(6):447–57. [Accessed 26 July 2017].
  270. Fava GA, Gatti A, Belaise C, Guidi J, Offidani E. Withdrawal symptoms after selective serotonin reuptake inhibitor discontinuation: A systematic review. Psychother Psychosom 2015;84(2):72–81. [Accessed 26 July 2017].
  271. Gallagher HC, Gallagher RM, Butler M, Buggy DJ, Henman MC. Venlafaxine for neuropathic pain in adults. Cochrane Database Syst Rev 2015;8:CD011091. [Accessed 26 July 2017].
  272. Lunn MP, Hughes RA, Wiffen PJ. Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia. Cochrane Database Syst Rev 2014;1:CD007115. [Accessed 26 July 2017].
  273. Kuijpers T, van Middelkoop M, Rubinstein SM, et al. A systematic review on the effectiveness of pharmacological interventions for chronic non-specific low-back pain. Eur Spine J 2011;20(1):40–50. [Accessed 26 July 2017].
  274. Urquhart DM, Hoving JL, Assendelft WW, Roland M, van Tulder MW. Antidepressants for non-specific low back pain. Cochrane Database Syst Rev 2008(1):CD001703. [Accessed 26 July 2017].
  275. Attal N, Cruccu G, Baron R, et al. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. Eur J Neurol 2010;17(9):1113–e88. [Accessed 26 July 2017].
  276. Moulin DE, Clark AJ, Gilron I, et al. Pharmacological management of chronic neuropathic pain – Consensus statement and guidelines from the Canadian Pain Society. Pain Res Manag 2007;12(1):13–21. [Accessed 26 July 2017].
  277. Bril V, England J, Franklin GM, et al. Evidence-based guideline: Treatment of painful diabetic neuropathy: Report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology 2011;76(20):1758–65. [Accessed 26 July 2017].
  278. Saarto T, Wiffen PJ. Antidepressants for neuropathic pain. Cochrane Database Syst Rev 2007(4):CD005454. [Accessed 26 July 2017].
  279. Rudroju N, Bansal D, Talakokkula ST, et al. Comparative efficacy and safety of six antidepressants and anticonvulsants in painful diabetic neuropathy: A network meta-analysis. Pain Physician 2013;16(6):E705–14. [Accessed 26 July 2017].
  280. Hearn L, Derry S, Phillips T, Moore RA, Wiffen PJ. Imipramine for neuropathic pain in adults. Cochrane Database Syst Rev 2014;5:CD010769. [Accessed 26 July 2017].
  281. Hearn L, Moore RA, Derry S, Wiffen PJ, Phillips T. Desipramine for neuropathic pain in adults. Cochrane Database Syst Rev 2014;9:CD011003. [Accessed 26 July 2017].
  282. Moore RA, Derry S, Aldington D, Cole P, Wiffen PJ. [Accessed 26 July 2017].
  283. Amitriptyline for neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev 2012;12:CD008242. [Accessed 26 July 2017].
  284. Fox C, Richardson K, Maidment ID, et al. Anticholinergic medication use and cognitive impairment in the older population: The medical research council cognitive function and ageing study. J Am Geriatr Soc 2011;59(8):1477–83. [Accessed 26 July 2017].
  285. Wiffen PJ, Derry S, Moore RA, Kalso EA. Carbamazepine for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev 2014;4:CD005451. [Accessed 26 July 2017].
  286. McAlindon TE, Bannuru RR, Sullivan MC, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis Cartilage 2014;22(3):363–88. [Accessed 26 July 2017].
  287. Chappell AS, Ossanna MJ, Liu-Seifert H, et al. Duloxetine, a centrally acting analgesic, in the treatment of patients with osteoarthritis knee pain: A 13-week, randomized, placebocontrolled trial. Pain 2009;146(3):253–60. [Accessed 26 July 2017].
  288. Myers J, Wielage RC, Han B, et al. The efficacy of duloxetine, non-steroidal anti-inflammatory drugs, and opioids in osteoarthritis: A systematic literature review and meta-analysis. BMC Musculoskelet Disord 2014;15:76. [Accessed 26 July 2017].
  289. Goldstein DJ, Lu Y, Detke MJ, Lee TC, Iyengar S. Duloxetine vs. placebo in patients with painful diabetic neuropathy. Pain 2005;116(1-2):109–18. [Accessed 26 July 2017].
  290. Smith EM, Pang H, Cirrincione C, et al. Effect of duloxetine on pain, function, and quality of life among patients with chemotherapy-induced painful peripheral neuropathy: A randomized clinical trial. JAMA 2013;309(13):1359–67. [Accessed 26 July 2017].
  291. Hauser W, Urrutia G, Tort S, Uceyler N, Walitt B. Serotonin and noradrenaline reuptake inhibitors (SNRIs) for fibromyalgia syndrome. Cochrane Database Syst Rev 2013;1:CD010292. [Accessed 26 July 2017].
  292. Sultan A, Gaskell H, Derry S, Moore RA. Duloxetine for painful diabetic neuropathy and fibromyalgia pain: Systematic review of randomised trials. BMC Neurol 2008;8:29. [Accessed 26 July 2017].
  293. Wiffen PJ, Derry S, Moore RA, et al. Antiepileptic drugs for neuropathic pain and fibromyalgia – An overview of Cochrane reviews. Cochrane Database Syst Rev 2013;11:CD010567. [Accessed 26 July 2017].
  294. Moore RA, Wiffen PJ, Derry S, Toelle T, Rice AS. Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev 2014;4:CD007938. [Accessed 26 July 2017].
  295. Snedecor SJ, Sudharshan L, Cappelleri JC, et al. Systematic review and meta-analysis of pharmacological therapies for pain associated with postherpetic neuralgia and less common neuropathic conditions. Int J Clin Pract 2014;68(7):900–18. [Accessed 26 July 2017].
  296. Moore RA, Straube S, Wiffen PJ, Derry S, McQuay HJ. Pregabalin for acute and chronic pain in adults. Cochrane Database Syst Rev 2009(3):CD007076. [Accessed 26 July 2017].
  297. Gordh TE, Stubhaug A, Jensen TS, et al. Gabapentin in traumatic nerve injury pain: A randomized, double-blind, placebo-controlled, cross-over, multi-center study. Pain 2008;138(2):255–66. [Accessed 26 July 2017].
  298. Uceyler N, Sommer C, Walitt B, Hauser W. Anticonvulsants for fibromyalgia. Cochrane Database Syst Rev 2013;10:CD010782. [Accessed 26 July 2017].
  299. Schifano F. Misuse and abuse of pregabalin and gabapentin: Cause for concern? CNS Drugs 2014;28(6):491–96. [Accessed 26 July 2017].
  300. Canadian Agency for Drugs and Technologies in Health. Abuse and misuse potential of pregabalin: A review of the clinical evidence. Ottawa: CADTH, 2012. Available at www. Pregabalin draft report Final.pdf [Accessed 26 July 2017].
  301. National Health Service (NHS) England. Advice for prescribers on the risk of the misuse of pregabalin and gabapentin: Public Health England, 2014. Available at www. data/file/385791/PHE-NHS_England_pregabalin_and_ gabapentin_advice_Dec_2014.pdf [Accessed 26 July 2017].
  302. Gill D, Derry S, Wiffen PJ, Moore RA. Valproic acid and sodium valproate for neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev 2011(10):CD009183. [Accessed 26 July 2017].
  303. Moore RA, Derry S, Wiffen PJ. Challenges in design and interpretation of chronic pain trials. Br J Anaesth 2013;111(1):38–45. [Accessed 26 July 2017].
  304. Moore RA, Straube S, Paine J, Derry S, McQuay HJ. Minimum efficacy criteria for comparisons between treatments using individual patient meta-analysis of acute pain trials: Examples of etoricoxib, paracetamol, ibuprofen, and ibuprofen/paracetamol combinations after third molar extraction. Pain 2011;152(5):982–89. [Accessed 26 July 2017].
  305. Moore RA, Smugar SS, Wang H, Peloso PM, Gammaitoni A. Numbers-needed-to-treat analyses – Do timing, dropouts, and outcome matter? Pooled analysis of two randomized, placebo-controlled chronic low back pain trials. Pain 2010;151(3):592–97. [Accessed 26 July 2017].
  306. Moore RA, Moore OA, Derry S, Peloso PM, Gammaitoni AR, Wang H. Responder analysis for pain relief and numbers needed to treat in a meta-analysis of etoricoxib osteoarthritis trials: Bridging a gap between clinical trials and clinical practice. Ann Rheum Dis 2010;69(2):374–79. [Accessed 26 July 2017].
  307. Lin HY, Cheng TT, Wang JH, et al. Etoricoxib improves pain, function and quality of life: Results of a real-world effectiveness trial. Int J Rheum Dis 2010;13(2):144–50. [Accessed 26 July 2017].
  308. Andrew Moore R, Eccleston C, Derry S, et al. ‘Evidence’ in chronic pain – Establishing best practice in the reporting of systematic reviews. Pain 2010;150(3):386–89. [Accessed 26 July 2017].
  309. Moore A. What works for whom? Determining the efficacy and harm of treatments for pain. Pain 2013;154 Suppl 1:S77–S86. [Accessed 26 July 2017].
  310. Moore RA, Straube S, Aldington D. Pain measures and cut-offs – ‘No worse than mild pain’ as a simple, universal outcome. Anaesthesia 2013;68(4):400–12. [Accessed 26 July 2017].
  311. Andrew R, Derry S, Taylor RS, Straube S, Phillips CJ. The costs and consequences of adequately managed chronic non-cancer pain and chronic neuropathic pain. Pain Pract 2014;14(1):79–94. [Accessed 26 July 2017].
  312. Machado GC, Maher CG, Ferreira PH, et al. Efficacy and safety of paracetamol for spinal pain and osteoarthritis: [Accessed 26 July 2017].
  313. Systematic review and meta-analysis of randomised placebo controlled trials. BMJ 2015;350:h1225. [Accessed 26 July 2017].
  314. da Costa BR, Reichenbach S, Keller N, et al. Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: A network metaanalysis. Lancet 2016;387(10033):2093–105. [Accessed 26 July 2017].
  315. Enthoven WT, Roelofs PD, Deyo RA, van Tulder MW, Koes BW. Non-steroidal anti-inflammatory drugs for chronic low back pain. Cochrane Database Syst Rev 2016;2:CD012087. [Accessed 26 July 2017].
  316. Colson J, Koyyalagunta D, Falco FJ, Manchikanti L. A systematic review of observational studies on the effectiveness of opioid therapy for cancer pain. Pain Physician 2011;14(2):E85–102. [Accessed 26 July 2017].
  317. Caraceni A, Hanks G, Kaasa S, et al. Use of opioid analgesics in the treatment of cancer pain: Evidencebased recommendations from the EAPC. Lancet Oncol 2012;13(2):e58–68. [Accessed 26 July 2017].
  318. National Institute for Health and Clinical Excellence. Opioids in palliative care: Safe and effective prescribing of strong opioids for pain in palliative care of adults. NICE guidelines CG140 2012 cg140 [Accessed 26 July 2017].
  319. Amato L, Davoli M, Perucci CA, Ferri M, Faggiano F, Mattick RP. An overview of systematic reviews of the effectiveness of opiate maintenance therapies: Available evidence to inform clinical practice and research. J Subst Abuse Treat 2005;28(4):321–29. [Accessed 26 July 2017].
  320. Harrison CM, Charles J, Henderson J, Britt H. Opioid prescribing in Australian general practice. Med J Aust 2012;196(6):380–81. [Accessed 26 July 2017].
  321. Manchikanti L, Ailinani H, Koyyalagunta D, et al. A systematic review of randomized trials of long-term opioid management for chronic non-cancer pain. Pain Physician 2011;14(2):91–121. [Accessed 26 July 2017].
  322. Karlsson M, Berggren AC. Efficacy and safety of lowdose transdermal buprenorphine patches (5, 10, and 20 microg/h) versus prolonged-release tramadol tablets (75, 100, 150, and 200 mg) in patients with chronic osteoarthritis pain: A 12-week, randomized, open-label, controlled, parallel-group noninferiority study. Clin Ther 2009;31(3):503–13. [Accessed 26 July 2017].
  323. Buynak R, Shapiro DY, Okamoto A, et al. Efficacy and safety of tapentadol extended release for the management of chronic low back pain: Results of a prospective, randomized, double-blind, placebo- and activecontrolled Phase III study. Expert Opin Pharmacother 2010;11(11):1787–804. [Accessed 26 July 2017].
  324. Chaparro LE, Furlan AD, Deshpande A, Mailis-Gagnon A, Atlas S, Turk DC. Opioids compared to placebo or other treatments for chronic low-back pain. Cochrane Database Syst Rev 2013(8):CD004959. [Accessed 26 July 2017].
  325. Abdel Shaheed C, Maher CG, Williams KA, Day R, McLachlan AJ. Efficacy, tolerability, and dose-dependent effects of opioid analgesics for low back pain: A systematic review and meta-analysis. JAMA Intern Med 2016;176(7):958–68. [Accessed 26 July 2017].
  326. Steiner DJ, Sitar S, Wen W, et al. Efficacy and safety of the seven-day buprenorphine transdermal system in opioid-naive patients with moderate to severe chronic low back pain: An enriched, randomized, double-blind, placebo-controlled study. J Pain Symptom Manage 2011;42(6):903–17. [Accessed 26 July 2017].
  327. Vorsanger GJ, Xiang J, Gana TJ, Pascual ML, Fleming RR. Extended-release tramadol (tramadol ER) in the treatment of chronic low back pain. J Opioid Manag 2008;4(2):87–97. [Accessed 26 July 2017].
  328. Peloso PM, Fortin L, Beaulieu A, Kamin M, Rosenthal N, Protocol TRPCANSG. Analgesic efficacy and safety of tramadol/ acetaminophen combination tablets (Ultracet) in treatment of chronic low back pain: A multicenter, outpatient, randomized, double blind, placebo controlled trial. J Rheumatol 2004;31(12):2454–63. [Accessed 26 July 2017].
  329. Ruoff GE, Rosenthal N, Jordan D, Karim R, Kamin M, Protocol C-SG. Tramadol/acetaminophen combination tablets for the treatment of chronic lower back pain: A multicenter, randomized, double-blind, placebo-controlled outpatient study. Clin Ther 2003;25(4):1123–41. [Accessed 26 July 2017].
  330. Hauser W, Bock F, Engeser P, Tolle T, Willweber-Strumpfe A, Petzke F. Long-term opioid use in non-cancer pain. Dtsch Arztebl Int 2014;111(43):732–40. [Accessed 26 July 2017].
  331. Gaskell H, Derry S, Stannard C, Moore RA. Oxycodone for neuropathic pain in adults. Cochrane Database Syst Rev 2016;7:CD010692. [Accessed 26 July 2017].
  332. Chaparro LE, Wiffen PJ, Moore RA, Gilron I. Combination pharmacotherapy for the treatment of neuropathic pain in adults. Cochrane Database Syst Rev 2012;7:CD008943. [Accessed 26 July 2017].
  333. The Pharmaceutical Benefits Scheme (PBS) Drug Utilisation Sub-committee (DUSC). Opioid analgesics: Overview. [Accessed 26 July 2017].
  334. Canberra: Australian Government Department of Health, 2014 participants/public-release-docs/opioid-analgesics-overview [Accessed 26 July 2017].
  335. Licina L, Hamsher C, Lautenschager K, Dhanjal S, Williams N, Spevak C. Buprenorphine/naloxone therapy for opioid refractory neuropathic pain following traumatic amputation: A case series. Mil Med 2013;178(7):e858–61. [Accessed 26 July 2017].
  336. Simpson RW, Wlodarczyk JH. Transdermal buprenorphine relieves neuropathic pain: A randomized, double-blind, parallel-group, placebo-controlled trial in diabetic peripheral neuropathic pain. Diabetes Care 2016;39(9):1493–500. [Accessed 26 July 2017].
  337. Guetti C, Angeletti C, Marinangeli F, et al. Transdermal buprenorphine for central neuropathic pain: Clinical reports. Pain Pract 2011;11(5):446–52. [Accessed 26 July 2017].
  338. Wiffen PJ, Derry S, Moore RA, et al. Buprenorphine for neuropathic pain in adults. Cochrane Database Syst Rev 2015(9):CD011603. [Accessed 26 July 2017].
  339. Pergolizzi J, Aloisi AM, Dahan A, et al. Current knowledge of buprenorphine and its unique pharmacological profile. Pain Pract 2010;10(5):428–50. [Accessed 26 July 2017].
  340. Kress HG. Clinical update on the pharmacology, efficacy and safety of transdermal buprenorphine. Eur J Pain 2009;13(3):219–30. [Accessed 26 July 2017].
  341. Dahan A, Yassen A, Romberg R, et al. Buprenorphine induces ceiling in respiratory depression but not in analgesia. Br J Anaesth 2006;96(5):627–32. [Accessed 26 July 2017].
  342. Boom M, Niesters M, Sarton E, Aarts L, Smith TW, Dahan A. Non-analgesic effects of opioids: Opioid-induced respiratory depression. Curr Pharm Des 2012;18(37):5994–6004. [Accessed 26 July 2017].
  343. Hunter Integrated Pain Service. Health professional resources: Opioid selection. Newcastle: Hunter New England Health, 2013 au/__data/assets/pdf_file/0003/212961/Opioid_Selection. pdf [Accessed 26 July 2017].
  344. Crews KR, Gaedigk A, Dunnenberger HM, et al. Clinical pharmacogenetics implementation consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update. Clin Pharmacol Ther 2014;95(4):376–82. [Accessed 26 July 2017].
  345. Lotsch J. Opioid metabolites. J Pain Symptom Manage 2005;29(5 Suppl):S10–24. [Accessed 26 July 2017].
  346. Kirchheiner J, Schmidt H, Tzvetkov M, et al. Pharmacokinetics of codeine and its metabolite morphine in ultra-rapid metabolizers due to CYP2D6 duplication. Pharmacogenomics J 2007;7(4):257–65. [Accessed 26 July 2017].
  347. Vowles KE, McEntee ML, Julnes PS, Frohe T, Ney JP, van der Goes DN. Rates of opioid misuse, abuse, and addiction in chronic pain: A systematic review and data synthesis. Pain 2015;156(4):569–76. [Accessed 26 July 2017].
  348. Derry S, Moore RA, McQuay HJ. Single dose oral codeine, as a single agent, for acute postoperative pain in adults. Cochrane Database Syst Rev 2010(4):CD008099. [Accessed 26 July 2017].
  349. Derry S, Karlin SM, Moore RA. Single dose oral ibuprofen plus codeine for acute postoperative pain in adults. Cochrane Database Syst Rev 2015;2:CD010107. [Accessed 26 July 2017].
  350. Buckley NA, Faunce TA. Trials and tribulations in the removal of dextropropoxyphene from the Australian Register of Therapeutic Goods. Med J Aust 2013;199(4):257–60. [Accessed 26 July 2017].
  351. Collins SL, Edwards JE, Moore RA, McQuay HJ. Single dose dextropropoxyphene, alone and with paracetamol (acetaminophen), for postoperative pain. Cochrane Database Syst Rev 2000(2):CD001440. [Accessed 26 July 2017].
  352. Li Wan Po A, Zhang WY. Systematic overview of co-proxamol to assess analgesic effects of addition of dextropropoxyphene to paracetamol. BMJ 1997;315(7122):1565–71. [Accessed 26 July 2017].
  353. Grape S, Schug SA, Lauer S, Schug BS. Formulations of fentanyl for the management of pain. Drugs 2010;70(1):57–72. [Accessed 26 July 2017].
  354. Roxburgh A, Ritter A, Slade T, Burns L. Trends in drug use and related harms in Australia, 2001 to 2013. Sydney: National Drug and Alcohol Research Centre, University of New South Wales, 2013. [Accessed 26 July 2017].
  355. Quigley C. Hydromorphone for acute and chronic pain. Cochrane Database Syst Rev 2002(1):CD003447. [Accessed 26 July 2017].
  356. Felden L, Walter C, Harder S, et al. Comparative clinical effects of hydromorphone and morphine: A meta-analysis. Br J Anaesth 2011;107(3):319–28. [Accessed 26 July 2017].
  357. Lugo RA, Satterfield KL, Kern SE. Pharmacokinetics of methadone. J Pain Palliat Care Pharmacother 2005;19(4):13–24. [Accessed 26 July 2017].
  358. Weschules DJ, Bain KT, Richeimer S. Actual and potential drug interactions associated with methadone. Pain Med 2008;9(3):315–44. [Accessed 26 July 2017].
  359. Fredheim OM, Moksnes K, Borchgrevink PC, Kaasa S, Dale O. Clinical pharmacology of methadone for pain. Acta Anaesthesiol Scand 2008;52(7):879–89. [Accessed 26 July 2017].
  360. Weschules DJ, Bain KT. A systematic review of opioid conversion ratios used with methadone for the treatment of pain. Pain Med 2008;9(5):595–612. [Accessed 26 July 2017].
  361. Klimas R, Mikus G. Morphine-6-glucuronide is responsible for the analgesic effect after morphine administration: A quantitative review of morphine, morphine-6glucuronide, and morphine-3-glucuronide. Br J Anaesth 2014;113(6):935–44. [Accessed 26 July 2017].
  362. Faura CC, Collins SL, Moore RA, McQuay HJ. Systematic review of factors affecting the ratios of morphine and its major metabolites. Pain 1998;74(1):43–53. [Accessed 26 July 2017].
  363. Klepstad P, Dale O, Kaasa S, et al. Influences on serum concentrations of morphine, M6G and M3G during routine clinical drug monitoring: A prospective survey in 300 adult cancer patients. Acta Anaesthesiol Scand 2003;47(6):725–31. [Accessed 26 July 2017].
  364. Vallejo R, de Leon-Casasola O, Benyamin R. Opioid therapy and immunosuppression: A review. Am J Ther 2004;11(5):354–65. [Accessed 26 July 2017].
  365. Budd K. Pain management: Is opioid immunosuppression a clinical problem? Biomed Pharmacother 2006;60(7):310–17. [Accessed 26 July 2017].
  366. Lalovic B, Kharasch E, Hoffer C, Risler L, Liu-Chen LY, Shen DD. Pharmacokinetics and pharmacodynamics of oral oxycodone in healthy human subjects: Role of circulating active metabolites. Clin Pharmacol Ther 2006;79(5):461–79. [Accessed 26 July 2017].
  367. Samer CF, Daali Y, Wagner M, et al. Genetic polymorphisms and drug interactions modulating CYP2D6 and CYP3A activities have a major effect on oxycodone analgesic efficacy and safety. Br J Pharmacol 2010;160(4):919–30. [Accessed 26 July 2017].
  368. Zwisler ST, Enggaard TP, Mikkelsen S, Brosen K, Sindrup SH. Impact of the CYP2D6 genotype on post-operative intravenous oxycodone analgesia. Acta Anaesthesiol Scand 2010;54(2):232–40. [Accessed 26 July 2017].
  369. Kokki H, Kokki M, Sjovall S. Oxycodone for the treatment of postoperative pain. Expert Opin Pharmacother 2012;13(7):1045–58. [Accessed 26 July 2017].
  370. Olkkola KT, Kontinen VK, Saari TI, Kalso EA. Does the pharmacology of oxycodone justify its increasing use as an analgesic? Trends Pharmacol Sci 2013;34(4):206–14. [Accessed 26 July 2017].
  371. DePriest AZ, Miller K. Oxycodone/naloxone: Role in chronic pain management, opioid-induced constipation, and abuse deterrence. Pain Ther 2014;3(1):1–15. [Accessed 26 July 2017].
  372. Nieminen TH, Hagelberg NM, Saari TI, et al. St John’s wort greatly reduces the concentrations of oral oxycodone. Eur J Pain 2010;14(8):854–59. [Accessed 26 July 2017].
  373. Simopoulos TT, Smith HS, Peeters-Asdourian C, Stevens DS. Use of meperidine in patient-controlled analgesia and the development of a normeperidine toxic reaction. Arch Surg 2002;137(1):84–88. [Accessed 26 July 2017].
  374. Silverman ME, Shih RD, Allegra J. Morphine induces less nausea than meperidine when administered parenterally. J Emerg Med 2004;27(3):241–43. [Accessed 26 July 2017].
  375. Latta KS, Ginsberg B, Barkin RL. Meperidine: A critical review. Am J Ther 2002;9(1):53–68. [Accessed 26 July 2017].
  376. Benner KW, Durham SH. Meperidine restriction in a pediatric hospital. J Pediatr Pharmacol Ther 2011;16(3):185–90. [Accessed 26 July 2017].
  377. Tzschentke TM, Christoph T, Kogel BY. The mu-opioid receptor agonist/noradrenaline reuptake inhibition (MORNRI) concept in analgesia: The case of tapentadol. CNS Drugs 2014;28(4):319–29. [Accessed 26 July 2017].
  378. Vinik AI, Shapiro DY, Rauschkolb C, et al. A randomized withdrawal, placebo-controlled study evaluating the efficacy and tolerability of tapentadol extended release in patients with chronic painful diabetic peripheral neuropathy. Diabetes Care 2014;37(8):2302–9. [Accessed 26 July 2017].
  379. Raffa RB, Buschmann H, Christoph T, et al. Mechanistic and functional differentiation of tapentadol and tramadol. Expert Opin Pharmacother 2012;13(10):1437–49. [Accessed 26 July 2017].
  380. Riemsma R, Forbes C, Harker J, et al. Systematic review of tapentadol in chronic severe pain. Curr Med Res Opin 2011;27(10):1907–30. [Accessed 26 July 2017].
  381. Biondi DM, Xiang J, Etropolski M, Moskovitz B. Evaluation of blood pressure and heart rate in patients with hypertension who received tapentadol extended release for chronic pain: A post hoc, pooled data analysis. Clin Drug Investig 2014;34(8):565–76. [Accessed 26 July 2017].
  382. Xu XS, Smit JW, Lin R, Stuyckens K, Terlinden R, Nandy P. Population pharmacokinetics of tapentadol immediate release (IR) in healthy subjects and patients with moderate or severe pain. Clin Pharmacokinet 2010;49(10):671–82. [Accessed 26 July 2017].
  383. Kemp W, Schlueter S, Smalley E. Death due to apparent intravenous injection of tapentadol. J Forensic Sci 2013;58(1):288–91. [Accessed 26 July 2017].
  384. Dart RC, Cicero TJ, Surratt HL, Rosenblum A, Bartelson BB, Adams EH. Assessment of the abuse of tapentadol immediate release: The first 24 months. J Opioid Manag 2012;8(6):395–402. [Accessed 26 July 2017].
  385. Cepeda MS, Fife D, Ma Q, Ryan PB. Comparison of the risks of opioid abuse or dependence between tapentadol and oxycodone: Results from a cohort study. J Pain 2013;14(10):1227–41. [Accessed 26 July 2017].
  386. Cepeda MS, Fife D, Vo L, Mastrogiovanni G, Yuan Y. Comparison of opioid doctor shopping for tapentadol and oxycodone: A cohort study. J Pain 2013;14(2):158–64. [Accessed 26 July 2017].
  387. Wiffen PJ, Derry S, Naessens K, Bell RF. Oral tapentadol for cancer pain. Cochrane Database Syst Rev 2015;9:CD011460. [Accessed 26 July 2017].
  388. Afilalo M, Etropolski MS, Kuperwasser B, et al. Efficacy and safety of tapentadol extended release compared with oxycodone controlled release for the management of moderate to severe chronic pain related to osteoarthritis of the knee: A randomized, double-blind, placebo- and active-controlled phase III study. Clin Drug Investig 2010;30(8):489–505. [Accessed 26 July 2017].
  389. Lange B, Kuperwasser B, Okamoto A, et al. Efficacy and safety of tapentadol prolonged release for chronic osteoarthritis pain and low back pain. Adv Ther 2010;27(6):381–99. [Accessed 26 July 2017].
  390. Lee YK, Ko JS, Rhim HY, et al. Acute postoperative pain relief with immediate-release tapentadol: Randomized, double-blind, placebo-controlled study conducted in South Korea. Curr Med Res Opin 2014;30(12):2561–70. [Accessed 26 July 2017].
  391. Niesters M, Proto PL, Aarts L, Sarton EY, Drewes AM, Dahan A. Tapentadol potentiates descending pain inhibition in chronic pain patients with diabetic polyneuropathy. Br J Anaesth 2014;113(1):148–56. [Accessed 26 July 2017].
  392. Raffa RB, Friderichs E, Reimann W, Shank RP, Codd EE, Vaught JL. Opioid and nonopioid components independently contribute to the mechanism of action of tramadol, an ‘atypical’ opioid analgesic. J Pharmacol Exp Ther 1992;260(1):275–85. [Accessed 26 July 2017].
  393. Lee CR, McTavish D, Sorkin EM. Tramadol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in acute and chronic pain states. Drugs 1993;46(2):313–40. [Accessed 26 July 2017].
  394. Stamer UM, Lehnen K, Hothker F, et al. Impact of CYP2D6 genotype on postoperative tramadol analgesia. Pain 2003;105(1-2):231–38. [Accessed 26 July 2017].
  395. Radbruch L, Grond S, Lehmann KA. A risk-benefit assessment of tramadol in the management of pain. Drug Saf 1996;15(1):8–29. [Accessed 26 July 2017].
  396. Lim A, Schug S. Tramadol versus morphine as oral stepdown analgesia after postoperative epidural analgesia. Reg Anesth Pain Med 2001;26(2):S133. [Accessed 26 July 2017].
  397. Wilder-Smith CH, Hill L, Wilkins J, Denny L. Effects of morphine and tramadol on somatic and visceral sensory function and gastrointestinal motility after abdominal surgery. Anesthesiology 1999;91(3):639–47. [Accessed 26 July 2017].
  398. Tarkkila P, Tuominen M, Lindgren L. Comparison of respiratory effects of tramadol and oxycodone. J Clin Anesth 1997;9(7):582–85. [Accessed 26 July 2017].
  399. 380. Tarkkila P, Tuominen M, Lindgren L. Comparison of respiratory effects of tramadol and pethidine. Eur J Anaesthesiol 1998;15(1):64–68. [Accessed 26 July 2017].
  400. Jick H, Derby LE, Vasilakis C, Fife D. The risk of seizures associated with tramadol. Pharmacotherapy 1998;18(3):607–11. [Accessed 26 July 2017].
  401. Gasse C, Derby L, Vasilakis-Scaramozza C, Jick H. Incidence of first-time idiopathic seizures in users of tramadol. Pharmacotherapy 2000;20(6):629–34. [Accessed 26 July 2017].
  402. Nelson EM, Philbrick AM. Avoiding serotonin syndrome: The nature of the interaction between tramadol and selective serotonin reuptake inhibitors. Ann Pharmacother 2012;46(12):1712–16. [Accessed 26 July 2017].
  403. Radbruch L, Glaeske G, Grond S, et al. Topical review on the abuse and misuse potential of tramadol and tilidine in Germany. Subst Abus 2013;34(3):313–20. [Accessed 26 July 2017].
  404. Norrbrink C, Lundeberg T. Tramadol in neuropathic pain after spinal cord injury: A randomized, double-blind, placebo-controlled trial. Clin J Pain 2009;25(3):177–84. [Accessed 26 July 2017].
  405. Australian medicines handbook. Adelaide: Australian Medicines Handbook, 2015. Available at http://amhonline. [Accessed 26 July 2017].
  406. McQuay HJ. Opioid clinical pharmacology and routes of administration. Br Med Bull 1991;47(3):703–17. [Accessed 26 July 2017].
  407. Australian medicines handbook. Adelaide: Australian Medicines Handbook, 2015. Available at http://amhonline. [Accessed 26 July 2017].
  408. Public policy statement on the rights and responsibilities of health care professionals in the use of opioids for the treatment of pain: A consensus document from the American Academy of Pain Medicine, the American Pain Society, and the American Society of Addiction Medicine. Pain Med 2004;5(3):301–02. [Accessed 26 July 2017].
  409. Lee M, Silverman SM, Hansen H, Patel VB, Manchikanti L. A comprehensive review of opioid-induced hyperalgesia. Pain Physician 2011;14(2):145–61. [Accessed 26 July 2017].
  410. Low Y, Clarke CF, Huh BK. Opioid-induced hyperalgesia: [Accessed 26 July 2017].
  411. A review of epidemiology, mechanisms and management. Singapore Med J 2012;53(5):357–60. [Accessed 26 July 2017].
  412. Chang G, Chen L, Mao J. Opioid tolerance and hyperalgesia. Med Clin North Am 2007;91(2):199–211. [Accessed 26 July 2017].
  413. Mao J. Opioid-induced hyperalgesia. Pain: Clinical Updates 2008;16(2). Available at www. [Accessed 26 July 2017].
  414. Reznikov I, Pud D, Eisenberg E. Oral opioid administration and hyperalgesia in patients with cancer or chronic nonmalignant pain. Br J Clin Pharmacol 2005;60(3):311–18. [Accessed 26 July 2017].
  415. Ahmedzai SH, Boland J. Constipation in people prescribed opioids. BMJ Clin Evid 2006;12:2407. [Accessed 26 July 2017].
  416. Rosow CE, Gomery P, Chen TY, Stefanovich P, Stambler N, Israel R. Reversal of opioid-induced bladder dysfunction by intravenous naloxone and methylnaltrexone. Clin Pharmacol Ther 2007;82(1):48–53. [Accessed 26 July 2017].
  417. Kjellberg F, Tramer MR. Pharmacological control of opioid-induced pruritus: A quantitative systematic review of randomized trials. Eur J Anaesthesiol 2001;18(6):346–57. [Accessed 26 July 2017].
  418. Mujtaba S, Romero J, Taub CC. Methadone, QTc prolongation and torsades de pointes: Current concepts, management and a hidden twist in the tale? J Cardiovasc Dis Res 2013;4(4):229–35. [Accessed 26 July 2017].
  419. Fanoe S, Jensen GB, Sjogren P, Korsgaard MP, Grunnet M. Oxycodone is associated with dose-dependent QTc prolongation in patients and low-affinity inhibiting of hERG activity in vitro. Br J Clin Pharmacol 2009;67(2):172–79. [Accessed 26 July 2017].
  420. Lowenstein O, Leyendecker P, Lux EA, et al. Efficacy and safety of combined prolonged-release oxycodone and naloxone in the management of moderate/severe chronic non-malignant pain: Results of a prospectively designed pooled analysis of two randomised, double-blind clinical trials. BMC Clin Pharmacol 2010;10:12. [Accessed 26 July 2017].
  421. Soderberg KC, Laflamme L, Moller J. Newly initiated opioid treatment and the risk of fall-related injuries. A nationwide, register-based, case-crossover study in Sweden. CNS Drugs 2013;27(2):155–61. [Accessed 26 July 2017].
  422. Rolita L, Spegman A, Tang X, Cronstein BN. Greater number of narcotic analgesic prescriptions for osteoarthritis is associated with falls and fractures in elderly adults. J Am Geriatr Soc 2013;61(3):335–40. [Accessed 26 July 2017].
  423. Takkouche B, Montes-Martinez A, Gill SS, Etminan M. Psychotropic medications and the risk of fracture: A meta-analysis. Drug Saf 2007;30(2):171–84. [Accessed 26 July 2017].
  424. Teng Z, Zhu Y, Wu F, et al. Opioids contribute to fracture risk: A meta-analysis of 8 cohort studies. PLoS One 2015;10(6):e0128232. [Accessed 26 July 2017].
  425. Li L, Setoguchi S, Cabral H, Jick S. Opioid use for noncancer pain and risk of fracture in adults: A nested case-control study using the general practice research database. Am J Epidemiol 2013;178(4):559–69. [Accessed 26 July 2017].
  426. Kraut A, Shafer LA, Raymond CB. Proportion of opioid use due to compensated workers’ compensation claims in Manitoba, Canada. Am J Ind Med 2015;58(1):33–39. [Accessed 26 July 2017].
  427. Australasian Faculty of Occupational Medicine. [Accessed 26 July 2017].
  428. Compensable injuries and health outcomes. Sydney: RACP, 2001 pdf?sfvrsn=2 [Accessed 26 July 2017].
  429. Australasian Faculty of Occupational and Environmental Medicine. Helping people return to work: Using evidence for better outcomes. RACP, 2010. Available at www.workcover. people_return_to_work.pdf [Accessed 26 July 2017].
  430. Atlas SJ, Deyo RA. Evaluating and managing acute low back pain in the primary care setting. J Gen Intern Med 2001;16(2):120–31. [Accessed 26 July 2017].
  431. Hayden JA, Cartwright JL, Riley RD, Vantulder MW, Chronic Low Back Pain IPDM-AG. Exercise therapy for chronic low back pain: Protocol for an individual participant data metaanalysis. Syst Rev 2012;1:64. [Accessed 26 July 2017].
  432. Dahm KT, Brurberg KG, Jamtvedt G, Hagen KB. Advice to rest in bed versus advice to stay active for acute lowback pain and sciatica. Cochrane Database Syst Rev 2010(6):CD007612. [Accessed 26 July 2017].
  433. Drummer O. The role of drugs in road safety. Australian Prescriber 2008;31:33–35. [Accessed 26 July 2017].
  434. Wilhelmi BG, Cohen SP. A framework for ‘driving under the influence of drugs’ policy for the opioid using driver. Pain Physician 2012;15(3 Suppl):ES215–30. [Accessed 26 July 2017].
  435. Austroads. Assessing fitness to drive for commercial and private vehicle drivers. Sydney: Austroads, 2016 [Accessed 26 July 2017].
  436. Strand MC, Fjeld B, Arnestad M, Morland J. Can patients receiving opioid maintenance therapy safely drive? A systematic review of epidemiological and experimental studies on driving ability with a focus on concomitant methadone or buprenorphine administration. Traffic Inj Prev 2013;14(1):26–38. [Accessed 26 July 2017].
  437. Gomes T, Mamdani MM, Dhalla IA, Paterson JM, Juurlink DN.Opioid dose and drug-related mortality in patients with nonmalignant pain. Arch Intern Med 2011;171(7):686–91. [Accessed 26 July 2017].
  438. Sabatowski R, Mordenti G, Miceli L. Opioids and driving ability: Current data do not support one opioid being more favorable than another. Pain Pract 2014;14(2):196–97. [Accessed 26 July 2017].
  439. Kaye AM, Kaye AD, Lofton EC. Basic concepts in opioid prescribing and current concepts of opioid-mediated effects on driving. Ochsner J 2013;13(4):525–32. [Accessed 26 July 2017].
  440. Currow DC, Phillips J, Clark K. Using opioids in general practice for chronic non-cancer pain: An overview of current evidence. Med J Aust 2016;204(8):305–9. [Accessed 26 July 2017].
  441. Austroads. Assessing fitness to drive for commercial and private vehicle drivers. Sydney: Austroads, 2013. [Accessed 26 July 2017].
  442. Mailis-Gagnon A, Lakha SF, Furlan A, Nicholson K, Yegneswaran B, Sabatowski R. Systematic review of the quality and generalizability of studies on the effects of opioids on driving and cognitive/psychomotor performance. Clin J Pain 2012;28(6):542–55. [Accessed 26 July 2017].
  443. Drug and Alcohol Services South Australia. Prescription drugs and driving: Information for the prescriber. Adelaide: SA Health, 2014 wcm/connect/fe565c00452aa91abac9fa005ba75f87/Pr 2aa91abac9fa005ba75f87 [Accessed 26 July 2017].
  444. Dassanayake T, Michie P, Carter G, Jones A. Effects of benzodiazepines, antidepressants and opioids on driving: A systematic review and meta-analysis of epidemiological and experimental evidence. Drug Saf 2011;34(2):125–56. [Accessed 26 July 2017].
  445. Tan KH. Opioids and driving – A review. Australasian Anaesthesia, 2007. [Accessed 26 July 2017].
  446. Fishbain DA, Cutler RB, Rosomoff HL, Rosomoff RS. Are opioid-dependent/tolerant patients impaired in drivingrelated skills? A structured evidence-based review. J Pain Symptom Manage 2003;25(6):559–77. [Accessed 26 July 2017].
  447. Young T, Skatrud J, Peppard PE. Risk factors for obstructive sleep apnea in adults. JAMA 2004;291(16):2013–16. [Accessed 26 July 2017].
  448. Doufas AG, Tian L, Padrez KA, et al. Experimental pain and opioid analgesia in volunteers at high risk for obstructive sleep apnea. PLoS One 2013;8(1):e54807. [Accessed 26 July 2017].
  449. Mulier JP. Perioperative opioids aggravate obstructive breathing in sleep apnea syndrome: Mechanisms and alternative anesthesia strategies. Curr Opin Anaesthesiol 2016;29(1):129–33. [Accessed 26 July 2017].
  450. Lam KK, Kunder S, Wong J, Doufas AG, Chung F. Obstructive sleep apnea, pain, and opioids: Is the riddle solved? Curr Opin Anaesthesiol 2016;29(1):134–40. [Accessed 26 July 2017].
  451. Guilleminault C, Cao M, Yue HJ, Chawla P. Obstructive sleep apnea and chronic opioid use. Lung 2010;188(6):459–68. [Accessed 26 July 2017].
  452. Teichtahl H, Wang D. Sleep-disordered breathing with chronic opioid use. Expert Opin Drug Saf 2007;6(6):641–49. [Accessed 26 July 2017].
  453. Webster LR, Choi Y, Desai H, Webster L, Grant BJ. Sleepdisordered breathing and chronic opioid therapy. Pain Med 2008;9(4):425–32. [Accessed 26 July 2017].
  454. Ward CW. Safe use of opioids in individuals with obstructive sleep apnea. Pain Manag Nurs 2015;16(3):411–17. [Accessed 26 July 2017].
  455. Krebs EE, Paudel M, Taylor BC, et al. Association of opioids with falls, fractures, and physical performance among older men with persistent musculoskeletal pain. J Gen Intern Med 2016;31(5):463–69. [Accessed 26 July 2017].
  456. Milos V, Bondesson A, Magnusson M, et al. Fall riskincreasing drugs and falls: A cross-sectional study among elderly patients in primary care. BMC Geriatr 2014;14:40. [Accessed 26 July 2017].
  457. Abdulla A, Adams N, Bone M, et al. Guidance on the management of pain in older people. Age and Ageing 2013;42:i1–i57. [Accessed 26 July 2017].
  458. Makris UE, Abrams RC, Gurland B, Reid MC. Management of persistent pain in the older patient: A clinical review. JAMA 2014;312(8):825–36. [Accessed 26 July 2017].
  459. Solomon DH, Rassen JA, Glynn RJ, et al. The comparative safety of analgesics in older adults with arthritis. Arch Intern Med 2010;170(22):1968–76. [Accessed 26 July 2017].
  460. Wehling M. Non-steroidal anti-inflammatory drug use in chronic pain conditions with special emphasis on the elderly and patients with relevant comorbidities: Management and mitigation of risks and adverse effects. Eur J Clin Pharmacol 2014;70(10):1159–72. [Accessed 26 July 2017].
  461. Yang M, He M, Zhao M, et al. Proton pump inhibitors for preventing non-steroidal anti-inflammatory drug induced gastrointestinal toxicity: A systematic review. Curr Med Res Opin 2017:1–8. [Accessed 26 July 2017].
  462. Chau DL, Walker V, Pai L, Cho LM. Opiates and elderly: Use and side effects. Clin Interv Aging 2008;3(2):273–78. [Accessed 26 July 2017].
  463. McLachlan AJ, Bath S, Naganathan V, et al. Clinical pharmacology of analgesic medicines in older people: Impact of frailty and cognitive impairment. Br J Clin Pharmacol 2011;71(3):351–64. [Accessed 26 July 2017].
  464. Scott JC, Stanski DR. Decreased fentanyl and alfentanil dose requirements with age. A simultaneous pharmacokinetic and pharmacodynamic evaluation. J Pharmacol Exp Ther 1987;240(1):159–66. [Accessed 26 July 2017].
  465. Villesen HH, Banning AM, Petersen RH, et al. Pharmacokinetics of morphine and oxycodone following intravenous administration in elderly patients. Ther Clin Risk Manag 2007;3(5):961–67. [Accessed 26 July 2017].
  466. Macintyre PE, Jarvis DA. Age is the best predictor of postoperative morphine requirements. Pain 1996;64(2):357–64. [Accessed 26 July 2017].
  467. Woodhouse A, Mather LE. The influence of age upon opioid analgesic use in the patient-controlled analgesia (PCA) environment. Anaesthesia 1997;52(10):949–55. [Accessed 26 July 2017].
  468. Scott LJ, Perry CM. Tramadol: A review of its use in perioperative pain. Drugs 2000;60(1):139–76. [Accessed 26 July 2017].
  469. Barkin RL, Barkin SJ, Barkin DS. Perception, assessment, treatment, and management of pain in the elderly. Clin Geriatr Med 2005;21(3):465–90. [Accessed 26 July 2017].
  470. Upton RN, Semple TJ, Macintyre PE, Foster DJR. Population pharmacokinetic modelling of subcutaneous morphine in the elderly. Acute Pain 2006;8(3):109–16. [Accessed 26 July 2017].
  471. Davison SN. Pain in hemodialysis patients: Prevalence, cause, severity, and management. Am J Kidney Dis 2003;42(6):1239–47. [Accessed 26 July 2017].
  472. Humphreys BD, Soiffer RJ, Magee CC. Renal failure associated with cancer and its treatment: An update. J Am Soc Nephrol 2005;16(1):151–61. [Accessed 26 July 2017].
  473. Asconape JJ. Use of antiepileptic drugs in hepatic and renal disease. Handb Clin Neurol 2014;119:417–32. [Accessed 26 July 2017].
  474. 453. Raymond CB, Wazny LD, Honcharik PL. Pharmacotherapeutic options for the treatment of depression in patients with chronic kidney disease. Nephrol Nurs J 2008;35(3):257–63; quiz 64. [Accessed 26 July 2017].
  475. Conway BR, Fogarty DG, Nelson WE, Doherty CC. [Accessed 26 July 2017].
  476. Opiate toxicity in patients with renal failure. BMJ 2006;332(7537):345–46. [Accessed 26 July 2017].
  477. Nayak-Rao S. Achieving effective pain relief in patients with chronic kidney disease: A review of analgesics in renal failure. J Nephrol 2011;24(1):35–40. [Accessed 26 July 2017].
  478. Mercadante S, Arcuri E. Opioids and renal function. J Pain 2004;5(1):2–19. [Accessed 26 July 2017].
  479. Imani F, Motavaf M, Safari S, Alavian SM. The therapeutic use of analgesics in patients with liver cirrhosis: A literature review and evidence-based recommendations. Hepat Mon 2014;14(10):e23539. [Accessed 26 July 2017].
  480. Dwyer JP, Jayasekera C, Nicoll A. Analgesia for the cirrhotic patient: A literature review and recommendations. J Gastroenterol Hepatol 2014;29(7):1356–60. [Accessed 26 July 2017].
  481. Staton LJ, Panda M, Chen I, et al. When race matters: Disagreement in pain perception between patients and their physicians in primary care. J Natl Med Assoc 2007;99(5):532–38. [Accessed 26 July 2017].
  482. Merry B, Campbell CM, Buenaver LF, et al. Ethnic group differences in the outcomes of multidisciplinary pain treatment. J Musculoskelet Pain 2011;19(1):24–30. [Accessed 26 July 2017].
  483. Narayan MC. Culture’s effects on pain assessment and management. Am J Nurs 2010;110(4):38–47; quiz 8–9. [Accessed 26 July 2017].
  484. Shavers VL, Bakos A, Sheppard VB. Race, ethnicity, and pain among the U.S. adult population. J Health Care Poor Underserved 2010;21(1):177–220. [Accessed 26 July 2017].
  485. Somogyi AA, Barratt DT, Coller JK. Pharmacogenetics of opioids. Clin Pharmacol Ther 2007;81(3):429–44. [Accessed 26 July 2017].
  486. Stamer UM, Stuber F. Genetic factors in pain and its treatment. Curr Opin Anaesthesiol 2007;20(5):478–84. [Accessed 26 July 2017].
  487. McGrath P. ‘The biggest worry…’: Research findings on pain management for Aboriginal peoples in Northern Territory, Australia. Rural Remote Health 2006;6(3):549. [Accessed 26 July 2017].
  488. Fenwick C. Pain management strategies for health professionals caring for central Australian Aboriginal people. 1st edn. Canberra: Commonwealth Department of Health and Aged Care, 2001. [Accessed 26 July 2017].
  489. Fenwick C, Stevens J. Post operative pain experiences of central Australian Aboriginal women. What do we understand? Aust J Rural Health 2004;12(1):22–27. [Accessed 26 July 2017].
  490. Fenwick C. Assessing pain across the cultural gap: Central Australian Indigenous peoples’ pain assessment. Contemp Nurse 2006;22(2):218–27. [Accessed 26 July 2017].
  491. Australian Institute of Health and Welfare. The health and welfare of Australia’s Aboriginal and Torres Strait Islander people, an overview 2011. Cat. no. IHW 42. Canberra: AIWW, 2011. [Accessed 26 July 2017].
  492. Howe PW, Condon JR, Goodchild CS. Anaesthesia for Aboriginal Australians. Anaesth Intensive Care 1998;26(1):86–91. [Accessed 26 July 2017].
  493. Taylor K, Guerin P. Health care and Indigenous Australians: [Accessed 26 July 2017].
  494. Cultural safety in practice. Melbourne: Palgrave Macmillan, 2014. [Accessed 26 July 2017].
  495. Sabanovic H, Harris B, Clavisi O, Bywaters L. Attitudes towards opioids among patients prescribed medication in Victoria. Melbourne: Move Muscle, Bone & Joint Health, 2016 [Accessed 19 February 2017].
  496. Australian Institute of Health and Welfare. Back problems, associated comorbidities and risk factors Canberra: AIHW; 2016 [Accessed 29 July 2017].
  497. Arnow BA, Hunkeler EM, Blasey CM, et al. Comorbid depression, chronic pain, and disability in primary care. Psychosom Med 2006;68(2):262–68. [Accessed 29 July 2017].
  498. Knaster P, Estlander AM, Karlsson H, Kaprio J, Kalso E. Diagnosing depression in chronic pain patients: DSM-IV major depressive disorder vs. Beck depression inventory (BDI). PLoS One 2016;11(3):e0151982. [Accessed 29 July 2017].
  499. Burke AL, Mathias JL, Denson LA. Psychological functioning of people living with chronic pain: A metaanalytic review. Br J Clin Psychol 2015;54(3):345–60. [Accessed 29 July 2017].
  500. Primary Health Care Advisory Group. Primary Health Care Advisory Group final report: Better outcomes for people with chronic and complex health conditions. Canberra: Department of Health, 2016 54540CA257F72001102B9/$File/Primary-Health-Care-
  501. Advisory-Group_Final-Report.pdf [Accessed 12 July 2017].
  502. Manchikanti L, Kaye AM, Knezevic NN, et al. Responsible, safe, and effective prescription of opioids for chronic non-cancer pain: American Society of Interventional Pain Physicians (ASIPP) guidelines. Pain Physician 2017;20(2S):S3–S92.
  503. Robinson G. Prescription drug misuse: How to identify and manage drug seekers. BPJ 2008(16):18–23.
  504. Friese G, Wojciehoski R, Friese A. Drug seekers: Do you recognize the signs? Emerg Med Serv 2005;34(10):64–67, 88–89.
  505. Moeller KE, Lee KC, Kissack JC. Urine drug screening: Practical guide for clinicians. Mayo Clin Proc 2008; 83(1):66–76.
  506. Melzack R. The McGill Pain Questionnaire: Major properties and scoring methods. Pain 1975;1(3):277–99.
  507. Stein C, Mendl G. The German counterpart to McGill Pain Questionnaire. Pain 1988;32(2):251–55.
  508. Linton SJ, Boersma K. Early identification of patients at risk of developing a persistent back problem: The predictive validity of the Orebro Musculoskeletal Pain Questionnaire. Clin J Pain 2003;19(2):80–86.
  509. Linton SJ, Hallden K. Can we screen for problematic back pain? A screening questionnaire for predicting outcome in acute and subacute back pain. Clin J Pain 1998;14(3):209–15.
  510. Dunstan DA, Covic T, Tyson GA, Lennie IG. Does the Orebro Musculoskeletal Pain Questionnaire predict outcomes following a work-related compensable injury? Int J Rehabil Res 2005;28(4):369–70.
  511. Linton SJ, Ryberg M. A cognitive-behavioral group intervention as prevention for persistent neck and back pain in a non-patient population: a randomized controlled trial. Pain 2001;90(1–2):83–90.
  512. van den Hout JH, Vlaeyen JW, Heuts PH, Zijlema JH, Wijnen JA. Secondary prevention of work-related disability in nonspecific low back pain: Does problem-solving therapy help? A randomized clinical trial. Clin J Pain 2003;19(2):87– 96.
  513. Marhold C, Linton SJ, Melin L. A cognitive-behavioral return-to-work program: Effects on pain patients with a history of long-term versus short-term sick leave. Pain 2001;91(1–2):155–63.
  514. Linton SJ. Understanding pain for better clinical practice – A psychological perspective. Edinburgh: Elsevier, 2005.
This event attracts CPD points and can be self recorded

Did you know you can now log your CPD with a click of a button?

Create Quick log

Advertising