C. Peter N. Watson

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.

Neuropathic pain: a practical guide for the clinician

Neuropathic pain, caused by various central and peripheral nerve disorders, is especially problematic because of its severity, chronicity and resistance to simple analgesics. The condition affects 2%–3% of the population, is costly to the health care system and is personally devastating to the people who experience it. The diagnosis of neuropathic pain is based primarily on history (e.g., underlying disorder and distinct pain qualities) and the findings on physical examination (e.g., pattern of sensory disturbance); however, several tests may sometimes be helpful. Important pathophysiologic mechanisms include sodium-and calcium-channel upregulation, spinal hyperexcitability, descending facilitation and aberrant sympathetic–somatic nervous system interactions. Treatments are generally palliative and include conservative nonpharmacologic therapies, drugs and more invasive interventions (e.g., spinal cord stimulation). Individualizing treatment requires consideration of the functional impact of the neuropathic pain (e.g., depression, disability) as well as ongoing evaluation, patient education, reassurance and specialty referral. We propose a primary care algorithm for treatments with the most favourable risk–benefit profile, including topical lidocaine, gabapentin, pregabalin, tricyclic antidepressants, mixed serotonin–norepinephrine reuptake inhibitors, tramadol and opioids. The field of neuropathic pain research and treatment is in the early stages of development, with many unmet goals. In coming years, several advances are expected in the basic and clinical sciences of neuropathic pain, which will provide new and improved therapies for patients who continue to experience this disabling condition.

The epidemiological, clinical, and pathological rationale for the herpes zoster vaccine.

Worldwide, herpes zoster (HZ) affects millions of patients (particularly older adults) annually and causes significant suffering due to acute and chronic pain, or postherpetic neuralgia (PHN). The objective of this article is to explain the rationale for the HZ vaccine by summarizing data on the epidemiology of HZ in the immunocompetent host, with a focus on recent incidence and risk factor studies; to review information on the burden of HZ; and to discuss the challenges of lessening the morbidity of the disease. The incidence and severity of HZ and PHN are highest in older adults. Given the central nervous system damage caused by HZ, the difficulty of adequately treating HZ to prevent PHN, and the intractability of PHN, the advent of the HZ vaccine appears to be a crucial innovation for preventing HZ and PHN.

Antidepressant drugs as adjuvant analgesics

This article reviews the history of the use of antidepressants in painful states and traces the evolution of thinking from initially considering them as antidepressants to the current concept that they have an analgesic action. The greatest part of this paper considers chronic, nonmalignant, painful states and the evidence with each for the efficacy of some of these drugs. The mechanism of action, pharmacokinetics and adverse effects are discussed. Practical suggestions are made regarding their usage. Although antidepressants are imperfect analgesics because of limited efficacy and untoward effects, they may be the only avenue of relief for a painful condition. The correct choice of agent and proper administration are critical.

The prognosis with postherpetic neuralgia.

One hundred and fifty-six patients with moderate to severe postherpetic neuralgia (PHN) were followed for up to 11 years. Nearly half of all patients were doing well at the final assessment (median 2 years) and more than half of these were on no therapy at this time. The most commonly used agents associated with a good outcome were antidepressants, topical capsaicin and analgesics of various kinds. Longer duration PHN appeared to have a worse prognosis. More of these patients were noted to be using some form of treatment at follow up. A group of patients seemed to follow a progressive course and were refractory to all treatments used in this study.

Topical capsaicin as an adjuvant analgesic

Topical capsaicin has been studied in a variety of conditions by uncontrolled and controlled trials. It is attractive because it is a simple, safe treatment. Although these studies suggest an analgesic effect, even placebo-controlled trials have been impossible to blind due to the burning sensation induced by the capsaicin. A high placebo response rate in the controlled trials is an interesting observation and may account for the apparent salutary effect reported in the studies lacking a control. A careful scrutiny of the results of these trials to date as well as clinical experience indicate at best a modest effect with the currently available preparations with many patients failing to find relief, finding the relief unsatisfactory, or being unable to tolerate the burning sensation. Occasional patients appear to have a very good result, and these unusual cases may not be reflected by clinical trials. Topical capsaicin is generally not satisfactory as a sole therapy for chronic painful conditions, although it may serve as an adjuvant to other approaches.

Canadian Pain Society Position Statement on Pain Relief

The present report outlines key requirements that are central to helping patients manage pain effectively. Although current standards are available as guides for practice, the prevalence of pain suggests that many health professionals do not know and/or cannot relate to these standards. Therefore, a brief, pragmatic statement may be more useful initially for health professionals and patients learning about problematic pain outcomes. The principles in the brief statement produced by the Canadian Pain Society clarify and emphasize key underlying assumptions that have directed the development of many pain standards. The aim of the present paper is to increase awareness of ineffective pain practices and the importance of pain relief, and to stimulate further work in this area.

Herpes zoster and postherpetic neuralgia

See related research article by Drolet and colleagues, page [1731][1] “I wish I could state anything very satisfactory as to treatment of the after-pains, which are sometimes so severe as to make the patient weary of existence.” — William Bowman (1867) [1][2] Some progress has been made in

The long-term safety and efficacy of opioids: a survey of 84 selected patients with intractable chronic noncancer pain.

BACKGROUND The use of opioids for chronic noncancer pain (CNCP) remains controversial. Despite a number of randomized controlled trials showing efficacy and safety in the short term, long-term data are limited. OBJECTIVE To survey a selected cohort of patients with intractable CNCP with regard to long-term efficacy and safety of opioids. METHODS The present study reports long-term results from a survey of 84 patients with CNCP. The majority of patients had neuropathic pain, were treated with opioids and were followed every three months for a median of 8.4 years. Outcomes examined were pain severity, adverse effects, pain relief, satisfaction, mood, problematic opioid use, tolerance, physical dependency, functional status, health-related quality of life, immune status, sexual function, morbidity and mortality. Measures included a numerical rating scale, the Hospital Anxiety and Depression Scale, Brief Pain Inventory interference scale, Pain Disability Index and Short-Form Health Survey 12, version 2. RESULTS AND CONCLUSIONS Both long- and short-acting opioids were reported to be effective, with few significant long-term adverse effects in many subjects in the present selected cohort. The majority of patients reported at least 50% or greater pain relief and a moderate improvement in disability. Functional status and health-related quality of life scores were not severely affected. Problematic opioid use, tolerance and serious adverse effects, including constipation, were not major issues. The authors emphasize that the results obtained in the present selected group may not be generalizable to all CNCP patients in whom opioids are being initiated.

Herpes zoster and postherpetic neuralgia: past, present and future.

OBJECTIVES The history behind the current understanding of the varicella-zoster virus and its relationship to the pain conditions caused by shingles and postherpetic neuralgia are reviewed. The framework for the current conceptualization is Hope-Simpsons latency hypothesis. Data from recent work in virology, neuroanatomy and epidemiology are reviewed, as is work using varicella-zoster virus-infected animals. The recent data largely confirm Hope-Simpsons hypothesis and extend it significantly.