Dwight E. Moulin

Controlled-release oxycodone relieves neuropathic pain: a randomized controlled trial in painful diabetic neuropathy.

Background: Painful neuropathy is one of the most common long‐term complications of diabetes mellitus and often proves difficult to relieve. Methods: Patients with diabetic neuropathy with moderate or greater pain for at least 3 months, were evaluated for efficacy, safety and health‐related quality of life (QOL) while receiving controlled‐release (CR) oxycodone (OxyContin®) or active placebo. Patients underwent washout from all opioids 2–7 days before randomization to 10 mg CR oxycodone or active placebo (0.25 mg benztropine) q12h. The dose was increased, approximately weekly, to a maximum of 40 mg q12h CR oxycodone or 1 mg q12h benztropine, with crossover to the alternate treatment after a maximum of 4 weeks. Acetaminophen, 325–650 mg q4‐6h prn was provided as rescue. Results: Thirty‐six patients were evaluable for efficacy (21 men, 15 women, mean age 63.0±9.4 years). CR oxycodone resulted in significantly lower (P=0.0001) mean daily pain (21.8±20.7 vs. 48.6±26.6 mm VAS), steady pain (23.5±23.0 vs. 47.6±30.7 mm VAS), brief pain (21.8±23.5 vs. 46.7±30.8 mm VAS), skin pain (14.3±20.4 vs. 43.2±31.3 mm VAS), and total pain and disability (16.8±15.6 vs. 25.2±16.7; P=0.004). Scores from 6 of the 8 SF‐36 domains and both summary scales, Standardized Physical Component (P=0.0002) and Standardized Mental Component (P=0.0338) were significantly better during CR oxycodone treatment. The number needed to treat to obtain one patient with at least 50% pain relief is 2.6 and clinical effectiveness scores favoured treatment with CR oxycodone over placebo (P=0.0001). Conclusion: CR oxycodone is effective and safe for the management of painful diabetic neuropathy and improves QOL.

Chronic pain in Canada--prevalence, treatment, impact and the role of opioid analgesia.

OBJECTIVE To assess the prevalence, treatment and impact of chronic pain in Canada. METHODS A stratified random sample of 2012 adult Canadians (weighted by sex, age and region according to 1996 census data) was surveyed by telephone in 2001 to determine the prevalence of chronic pain, defined as continuous or intermittent pain for at least six months. A second sample of 340 chronic pain sufferers who were taking prescription medication for their pain was studied in detail to determine current therapeutic approaches and to assess the social and economic impact of chronic pain. RESULTS Chronic noncancer pain was reported by 29% of the respondents, with increased frequency in women and older age groups. The average duration of pain was 10.7 years and the average intensity was 6.3 (on a scale from 1 to 10), with 80% reporting moderate or severe pain. Anti-inflammatory agents were prescribed for 49% of respondents and opioid analgesics were prescribed for 22% (two-thirds of these were codeine). Almost 70% were worried about addiction potential, and one-third felt that strong analgesics should be reserved for terminal illnesses. Almost one-half were unable to attend social and family events, and the mean number of days absent from work in the past year due to chronic pain was 9.3. INTERPRETATION Chronic noncancer pain is common in Canadian adults and has a major social and economic impact. Despite growing evidence supporting the efficacy and safety of major opioid analgesics for chronic noncancer pain, less than 10% of chronic pain patients taking prescription medication were treated with a major opioid. Chronic pain is undertreated in Canada, and major opioid analgesics are probably underutilized in the management of moderate to severe pain as part of a multidisciplinary treatment program.

Pain syndromes in multiple sclerosis

To determine the prevalence and nature of pain in multiple sclerosis, we evaluated by questionnaire, interview, and chart review 159 patients residing in Middlesex County and followed in the MS Clinic at University Hospital, London, Ontario, Canada. Eighty-eight patients (55%) had either an acute or chronic pain syndrome at some time during their disease. Fifteen patients (9%) with acute pain syndromes had episodes of paroxysmal tic-like pain diagnosed in seven as trigeminal neuralgia. Chronic pain syndromes, present for a mean duration of 4.9 years, occurred in 76 patients (48%) and included dysesthetic extremity pain (29%), back pain (14%), painful leg spasms (13%), and abdominal pain (2%). MS patients with pain were similar to the pain-free group in mean age of onset (34.0 versus 31.9 years), average duration of disease (13.3 versus 12.1 years), spinal cord involvement (97% for each group), and mean rating on Kurtzke Disability Status Scale (4.2 versus 3.5). They differed in sex ratio with a higher female-to-male ratio in the pain group (3:1 versus 1.4:1). Chronic pain is a common feature of well-established MS and is usually associated with a myelopathy. Therapy must be individualized for each specific pain syndrome.

Use of opioid analgesics for the treatment of chronic noncancer pain - A consensus statement and guidelines from the Canadian Pain Society, 2002

The original document was approved by the Executive of the Canadian Pain Society on November 18, 1998 and the updated version was approved on November 5, 2002. 1Alcohol & Drug Treatment Program, Credit Valley Hospital, Mississauga, Ontario; 2Departments of Physical Medicine and Rehabilitation/Psychiatry, McMaster University, Hamilton, Ontario; 3Department of Anaesthesia, University of Toronto, Toronto, Ontario; St Michael’s Hospital Pain Clinic, Toronto, Ontario and Pain Management Programme, Sunnybrook and Women’s College Health Sciences Programme, Toronto, Ontario; 4Mount Sinai Hospital, Toronto, Ontario and Department of Family and Community Medicine, University of Toronto, Toronto, Ontario; 5Department of Family Medicine, University of Alberta, Edmonton, Alberta; 6Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia and Pain Management Unit, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia; 7Departments of Clinical Neurological Sciences and Oncology, University of Western Ontarion, London, Ontario Correspondence: Dr RD Jovey, Alcohol & Drug Treatment Program, Credit Valley Hospital, Suite G-01, 2300 Eglinton Avenue West, Mississauga, Ontario L5M 2V8. Telephone 905-813-4402, fax 905-567-0241, e-mail drjovey@sympatico.ca. RD Jovey, J Ennis, J Gardner-Nix, B Goldman, H Hays, M Lynch, D Moulin. Use of opioid analgesics for the treatment of chronic noncancer pain – A consenus statement and guidelines from the Canadian Pain Society, 2002. Pain Res Manage 2003;8(Suppl A):3A-14A.

2012 Canadian Guidelines for the diagnosis and management of fibromyalgia syndrome: executive summary.

BACKGROUND Recent neurophysiological evidence attests to the validity of fibromyalgia (FM), a chronic pain condition that affects >2% of the population. OBJECTIVES To present the evidence-based guidelines for the diagnosis, management and patient trajectory of individuals with FM. METHODS A needs assessment following consultation with diverse health care professionals identified questions pertinent to various aspects of FM. A literature search identified the evidence available to address these questions; evidence was graded according to the standards of the Oxford Centre for Evidence-Based Medicine. Drafted recommendations were appraised by an advisory panel to reflect meaningful clinical practice. RESULTS The present recommendations incorporate the new clinical concepts of FM as a clinical construct without any defining physical abnormality or biological marker, characterized by fluctuating, diffuse body pain and the frequent symptoms of sleep disturbance, fatigue, mood and cognitive changes. In the absence of a defining cause or cure, treatment objectives should be patient-tailored and symptom-based, aimed at reducing global complaints and enhancing function. Healthy lifestyle practices with active patient participation in health care forms the cornerstone of care. Multimodal management may include nonpharmacological and pharmacological strategies, although it must be acknowledged that pharmacological treatments provide only modest benefit. Maintenance of function and retention in the workforce is encouraged. CONCLUSIONS The new Canadian guidelines for the treatment of FM should provide health professionals with confidence in the complete care of these patients and improve clinical outcomes.

PAIN IN CENTRAL AND PERIPHERAL DEMYELINATING DISORDERS: Multiple Sclerosis and Guillain-Barré Syndrome

Moderate to severe pain is a common feature of central and peripheral demyelinating disorders. Pain in multiple sclerosis tends to occur when the disease is well-established and usually lingers infinitely. Pain in Guillain-Barré syndrome tends to be particularly severe at the time of initial presentation and usually resolves over 8 to 12 weeks. Pain in both conditions is generally caused by either the direct effects of nerve injury or the result of paralysis and prolonged immobilization. Pain syndromes are well-defined in each disorder based on the underlying pathophysiology. Treatment involves a variety of pharmacologic and nonpharmacologic approaches individualized for each specific pain syndrome.

A randomized, double-blind, placebo-controlled clinical trial using a low-frequency magnetic field in the treatment of musculoskeletal chronic pain

Exposure to a specific pulsed electromagnetic field (PEMF) has been shown to produce analgesic (antinociceptive) effects in many organisms. In a randomized, double-blind, sham-controlled clinical trial, patients with either chronic generalized pain from fibromyalgia (FM) or chronic localized musculoskeletal or inflammatory pain were exposed to a PEMF (400 microT) through a portable device fitted to their head during twice-daily 40 min treatments over seven days. The effect of this PEMF on pain reduction was recorded using a visual analogue scale. A differential effect of PEMF over sham treatment was noticed in patients with FM, which approached statistical significance (P=0.06) despite low numbers (n=17); this effect was not evident in those without FM (P=0.93; n=15). PEMF may be a novel, safe and effective therapeutic tool for use in at least certain subsets of patients with chronic, nonmalignant pain. Clearly, however, a larger randomized, double-blind clinical trial with just FM patients is warranted.

Buprenorphine transdermal system for opioid therapy in patients with chronic low back pain.

OBJECTIVE The present randomized, double-blinded, crossover study compared the efficacy and safety of a seven-day buprenorphine transdermal system (BTDS) and placebo in patients with low back pain of moderate or greater severity for at least six weeks. METHODS Prestudy analgesics were discontinued the evening before random assignment to 5 microg/h BTDS or placebo, with acetaminophen 300 mg/codeine 30 mg, one to two tablets every 4 h to 6 h as needed, for rescue analgesia. The dose was titrated to effect weekly, if tolerated, to 10 microg/h and 20 microg/h BTDS. Each treatment phase was four weeks. RESULTS Fifty-three patients (28 men, 25 women, mean [+/- SD] age 54.5+/-12.7 years) were evaluable for efficacy (completed two weeks or more in each phase). Baseline pain was 62.1+/-15.5 mm (100 mm visual analogue scale) and 2.5+/-0.6 (five-point ordinal scale). BTDS resulted in lower mean daily pain scores than in the placebo group (37.6+/-20.7 mm versus 43.6+/-21.2 mm on a visual analogue scale, P=0.0487; and 1.7+/-0.6 versus 2.0+/-0.7 on the ordinal scale, P=0.0358). Most patients titrated to the highest dose of BTDS (59% 20 microg/h, 31% 10 microg/h and 10% 5 microg/h). There were improvements from baseline in pain and disability (Pain Disability Index), Pain and Sleep (visual analogue scale), Quebec Back Pain Disability Scale and Short-Form 36 Health Survey scores for both BTDS and placebo groups, without significant differences between treatments. While there were more opioid-related side effects with BTDS treatment than with placebo, there were no serious adverse events. A total of 82% of patients chose to continue BTDS in a long-term open-label evaluation, in whom improvements in pain intensity, functionality and quality of life were sustained for up to six months without analgesic tolerance. CONCLUSION BTDS (5 microg/h to 20 microg/h) represents a new treatment option for initial opioid therapy in patients with chronic low back pain.

Comparative Efficacy and Safety of Controlled‐Release Morphine Suppositories and Tablets in Cancer Pain

Although the oral route is the preferred method of opioid therapy in patients with cancer pain, many patients will require an alternate route of analgesic administration at some point during the trajectory of their illness. This study compared the efficacy and safety of a novel, controlled‐release suppository of morphine (MSC‐R) and controlled‐release morphine tablets (MSC‐T) in patients with cancer pain. In a double‐blind crossover study, 27 patients with cancer pain were randomized to receive MSC‐R or MSC‐T every 12 hours for 7 days each, using a 1:1 analgesic equivalence ratio. Pain intensity was assessed using a visual analog scale (VAS) and the Present Pain Intensity Index of the McGill Pain Questionnaire. Nausea and sedation were also assessed with a VAS. Pharmacodynamic assessments were made by the patient at 8:00 am, 12:00 pm, 4:00 pm, and 8:00 pm and rescue morphine use recorded in a daily diary. There were no significant differences between MSC‐R and MSC‐T in overall scores for pain intensity VAS, ordinal pain intensity, and sedation. There was a small but significant difference in overall nausea VAS score in favor of MSC‐R. Mean daily rescue analgesic use did not differ significantly during between treatment with MSC‐R and MSC‐T. MSC‐R provides pain control comparable to that provided by MSC‐T when given every 12 hours at a 1:1 dose ratio, and represents a reliable alternative method of pain control for patients unable to take oral opioid agents.

Systemic drug treatment for chronic musculoskeletal pain

Objective: The purpose of this review was to determine how effective different classes of analgesic agents are in the management of chronic pain. Methodology: The literature search identified five systematic reviews and 18 randomized controlled trials to provide evidence about systemic drug treatment for chronic pain. Results: Studies in the systematic reviews were mainly of low back pain, and studies in the randomized controlled trials were mainly of fibromyalgia. Other studies investigated of rheumatic pain, musculoskeletal pain, chronic low back pain, and temporomandibular pain. Classes of analgesic agents reviewed were antidepressants, nonsteroidal anti-inflammatory drugs, muscle relaxants, opioid analgesics, and a number of miscellaneous agents. Conclusions: For chronic pain, opioid analgesics provide benefit for up to 9 weeks (level 2). For chronic low back pain, the evidence shows that various types of nonsteroidal antiinflammatory drugs are equally effective or ineffective, and that antidepressants provide no benefit in the short to intermediate term (level 2). Muscle relaxants showed limited effectiveness (level 3) for chronic neck pain and for chronic low back pain for up to 4 weeks. For fibromyalgia, there is limited evidence (level 3) of the effectiveness of amitryptiline, ondansetron, zoldipem, or growth hormone, and evidence of no effectiveness for nonsteroidal anti-inflammatory drugs, malic acid with magnesium, calcitonin injections, or s-adenyl-L-methionine. For temporomandibular pain, oral sumatriptan is not effective (level 2). The remaining evidence was inadequate (level 4a) or contradictory (level 4b).