McMaster University

Michael G. DeGroote
National Pain Centre

Scope of Search

Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain

Cluster 1: Deciding to Initiate Opioid Therapy

R04. Recommendation Statement

No. Recommendation Keyword
R04 Before initiating opioid therapy, consider the evidence related to effectiveness in patients with chronic non-cancer pain. (Grade A). Opioid efficacy
  • R04. Discussion
  • R04. Summary of Peer-Reviewed Evidence

R04. Discussion

The systematic review update (see Part A, 10: Literature Search Methods) completed to support this guideline examined the effectiveness of opioids for CNCP. A summary of findings includes:

  • Opioids were more effective than placebo for pain and function, irrespective of the type of opioid (strong or weak) or mechanism of pain (nociceptive or neuropathic).
  • The effect sizes of opioids over placebo were medium1 for pain and small for function. In other words, opioids work better for pain than for function.
  • One opioid (tramadol) was effective for fibromyalgia for pain and function; however there were only two randomized trials, and the effects sizes were small for both pain and function.

1For effect size, most authors use Cohen's three levels (REF Cohen, & REF 2009 Updated Method Guideline)


  • Mean difference less than 10% of the scale (e.g., <10mm on a 100 mm VAS).
  • ES  <0.5.


  • Mean difference 10 to 20% of the scale.
  • ES from 0.5 to <0.8.


  • Mean difference >20% of the scale.
  • ES ≥ 0.8.

Table B-4.1 Evidence of Opioid Efficacy

Examples of CNCP conditions for which opioids were shown to be effective in placebo-controlled trials * Examples of CNCP conditions that have NOT been studied in placebo-controlled trials
Tramadol only Weak or strong opioid  
  • Diabetic neuropathy
  • Peripheral neuropathy
  • Postherpetic neuralgia
  • Phantom limb pain
  • Spinal cord injury with pain below the level of injury
  • Lumbar radiculopathy
  • Osteoarthritis
  • Rheumatoid arthritis
  • Low-back pain
  • Neck pain
  •  Headache
  • Irritable bowel syndrome
  • Pelvic pain
  • Temporomandibular joint dysfunction
  • Atypical facial pain
  • Non-cardiac chest pain
  • Lyme disease
  • Whiplash
  • Repetitive strain Injury

* A limitation of these trials was that the duration of opioid therapy was a maximum of three months.

1. Nociceptive pain of musculoskeletal origin (e.g., osteoarthritis, low-back pain, neck pain)

Opioids showed only small to moderate benefits for nociceptive pain in improving function and relieving pain (Furlan 2006, Furlan unpublished 2010, Nuesch 2009). If opioids are required, patients generally respond to moderate doses. Acetaminophen, NSAIDs and non-pharmacological treatments are often effective for patients with low back pain and other common musculoskeletal problems.

2. Neuropathic pain

Opioids showed only small to moderate benefits for neuropathic pain (Furlan 2006, Furlan 2009, Eisenberg 2005). Patients with neuropathic pain may require higher opioid doses, in combination with tricyclic antidepressants (Khoromi 2007) or anticonvulsants (Gilron 2005).

3. Migraine, tension headache, functional GI problems

Opioids are usually not indicated for migraine or tension headaches, or for patients with functional gastro-intestinal problems such as irritable bowel syndrome (Bigal 2009).

4. Widespread soft tissue pain

The benefit of the weak opioid tramadol for fibromyalgia was small. Other pain-relief options should be considered.

R04. Summary of Peer-Reviewed Evidence

The updated systematic review of opioids for CNCP included 62 randomized trials (see Appendix B-13). Opioids were compared to placebos in 47 randomized trials. The effect size for improvement in pain was medium (0.58 95% confidence interval [CI]: 0.48 to 0.67, extracted from 47 RCTs). For functional outcomes, the effect size was small (0.34 95% CI: 0.25 to 0.43, extracted from 31 RCTs) (Furlan unpublished 2010).

1. Nociceptive pain and osteoarthritis.

The meta-analysis of 31 randomized trials of opioids for nociceptive pain showed a medium-effect size for pain relief outcomes (0.60 95% CI: 0.49 to 0.72, extracted from 31 trials), and small for functional outcomes (0.38 95% CI: 0.26 to 0.49, extracted from 21 trials) (Furlan unpublished 2010).

A recently published Cochrane review of opioids for osteoarthritis showed that the small-to-moderate beneficial effects of non-tramadol opioids are outweighed by large increases in the risk of adverse events. They concluded that non-tramadol opioids should therefore not be routinely used, even if osteoarthritic pain is severe (Nuesch 2009).

2. Neuropathic pain.

The meta-analysis of 13 randomized trials of opioids for neuropathic pain showed a medium effect size for pain relief outcomes (0.56 95% CI: 0.38  to 0.73, extracted from 13 trials), and small for functional outcomes (0.24 95% CI: 0.09  to 0.39, extracted from 7 trials) (Furlan unpublished 2010).

A fixed-effects model meta-analysis of 6 randomized trials of opioids for neuropathic pain showed mean post-treatment visual analog scale scores of pain intensity after opioids to be 14 units lower on a scale from 0 to 100 than after placebo (95% CI : −18 to −10; P<.001) (Eisenberg 2005).

3. Widespread soft tissue pain.

There are no randomized trials of strong opioids for fibromyalgia. There are two randomized trials of the weak opioid, tramadol for fibromyalgia. They showed small benefits in reducing pain (Russell 2000, Bennett 2003). The EULAR (European League Against Rheumatism) guidelines for the treatment of fibromyalgia recommend tramadol but not strong opioids (Carville 2008).