Pharmacological management of chronic neuropathic pain - consensus statement and guidelines from the Canadian Pain Society.

Neuropathic pain (NeP), generated by disorders of the peripheral and central nervous system, can be particularly severe and disabling. Prevalence estimates indicate that 2% to 3% of the population in the developed world suffer from NeP, which suggests that up to one million Canadians have this disabling condition. Evidence-based guidelines for the pharmacological management of NeP are therefore urgently needed. Randomized, controlled trials, systematic reviews and existing guidelines focusing on the pharmacological management of NeP were evaluated at a consensus meeting. Medications are recommended in the guidelines if their analgesic efficacy was supported by at least one methodologically sound, randomized, controlled trial showing significant benefit relative to placebo or another relevant control group. Recommendations for treatment are based on degree of evidence of analgesic efficacy, safety, ease of use and cost-effectiveness. Analgesic agents recommended for first-line treatments are certain antidepressants (tricyclics) and anticonvulsants (gabapentin and pregabalin). Second-line treatments recommended are serotonin noradrenaline reuptake inhibitors and topical lidocaine. Tramadol and controlled-release opioid analgesics are recommended as third-line treatments for moderate to severe pain. Recommended fourth-line treatments include cannabinoids, methadone and anticonvulsants with lesser evidence of efficacy, such as lamotrigine, topiramate and valproic acid. Treatment must be individualized for each patient based on efficacy, side-effect profile and drug accessibility, including cost. Further studies are required to examine head-to-head comparisons among analgesics, combinations of analgesics, long-term outcomes, and treatment of pediatric and central NeP.

Chronic noncancer pain and the long term utility of opioids.

OBJECTIVE: To report on a long term experience in treating patients with chronic noncancer pain (CNCP). METHODS: One hundred two patients with CNCP were seen every three months and followed for one year or more (median eight years, range one to 22). Demographic data, diagnostic categories and response to therapies were recorded. The utility and safety of opioid therapy, adverse events, impact on disability and issues related to previous psychiatric or chemical dependency history were documented. RESULTS: Most patients reported a variety of neuropathic pain problems and most required chronic opioid therapy after the failure of other treatments. Although 44% reported being satisfied with pain relief despite adverse events, it is noteworthy that the remaining patients chose to continue therapy for the modest benefit of pain relief despite adverse events. Moreover, 54% were less disabled on opioid therapy. CONCLUSIONS: This is a large sample of CNCP patients, most taking opioids over a long period of time. CNCP can be treated by opioids safely and with a modest effect, with improvement in functioning in some patients who are refractory to other measures. If care is taken, opioids may even be used effectively for patients with a history of chemical dependency.

Post-herpetic neuralgia: further post-mortem studies of cases with and without pain.

The pathological features associated with post-herpetic neuralgia require further study. We report here 5 cases, 3 with severe post-herpetic neuralgia (PHN) and 2 with no persistent pain. The findings of dorsal horn atrophy and cell, axon and myelin loss with fibrosis in the sensory ganglion were found only in patients with persistent pain. Marked loss of myelin and axons in the nerve and/or sensory root were found in cases with and without pain. Some evidence is presented for a more generalized subacute or chronic inflammatory process which may explain the clinical features of some patients. Further studies will be necessary to fully describe the morbid anatomy of this disorder.

Post-herpetic neuralgia: post-mortem analysis of a case.

The morphological and biochemical substrates of the severe pain in post-herpetic neuralgia (PHN) are unclear. This report is an autopsy study of a 67-year-old male with severe PHN during the last 5 years of his life over the right T7-8 dermatomes. The dorsal horn of the thoracic spinal cord of the affected side was atrophic from T4 to T8, with loss of both myelin and axons. Despite this, only the T8 ganglion was affected by fibrosis and cell loss and only the nerve roots at that level appeared affected. Markers of unmyelinated afferents (substance P), substantia gelatinosa neurons (opiate receptors), glial cells (glial fibrillary acidic protein), and descending spinal projections (dopamine-beta-hydroxylase and serotonin) were not different at affected versus non-affected spinal cord levels. The pain of PHN may result from the uninhibited activity of unmyelinated primary afferents as a result of the loss of myelinated afferent fibers and the possible presence of hypersensitive neurons in the dorsal horn.

A comparative trial of amitriptyline and zimelidine in post-herpetic neuralgia.

Serotoninergic pathways are believed to be important in pain mechanisms. Accordingly, we studied the action of zimelidine, a very highly serotoninergic antidepressant, in relieving the pain of post-herpetic neuralgia. Fifteen patients received zimelidine and amitriptyline in that order in an open-label cross-over study. Only one patient with zimelidine obtained a good result, whereas 8 patients on amitriptyline amitriptyline has a pain-relieving action, at least in post-herpetic neuralgia, which is not primarily linked with its serotoninergic effects and which is also independent of its effects on depression.