The Effect of Once-Daily Gabapentin Extended Release Formulation in Patients With Postamputation Pain

New studies of the treatment of neuropathic pain have increased the need for an updated review of randomized, double-blind, placebo-controlled trials to support an evidence based algorithm to treat neuropathic pain conditions. Available studies were identified using a MEDLINE and EMBASE search. One hundred and five studies were included. Numbers needed to treat (NNT) and numbers needed to harm (NNH) were used to compare efficacy and safety of the treatments in different neuropathic pain syndromes. The quality of each trial was assessed. Tricyclic antidepressants and the anticonvulsants gabapentin and pregabalin were the most frequently studied drug classes. In peripheral neuropathic pain, the lowest NNT was for tricyclic antidepressants, followed by opioids and the anticonvulsants gabapentin and pregabalin. For central neuropathic pain there is limited data. NNT and NNH are currently the best way to assess relative efficacy and safety, but the need for dichotomous data, which may have to be estimated retrospectively for old trials, and the methodological complexity of pooling data from small cross-over and large parallel group trials, remain as limitations.

Peripheral tissue damage or nerve injury often leads to pathological pain processes, such as spontaneous pain, hyperalgesia and allodynia, that persist for years or decades after all possible tissue healing has occurred. Although peripheral neural mechanisms, such as nociceptor sensitization and neuroma formation, contribute to these pathological pain processes, recent evidence indicates that changes in central neural function may also play a significant role. In this review, we examine the clinical and experimental evidence which points to a contribution of central neural plasticity to the development of pathological pain. We also assess the physiological, biochemical, cellular and molecular mechanisms that underlie plasticity induced in the central nervous system (CNS) in response to noxious peripheral stimulation. Finally, we examine theories which have been proposed to explain how injury or noxious stimulation lead to alterations in CNS function which influence subsequent pain experience.

Patients with neuropathic pain (NeuP) experience substantially lower health-related quality of life (HRQoL) than the general population. The aim of this systematic review and meta-analysis is to test the hypothesis that NeuP is associated with low levels of health utility. A structured search of electronic databases (MEDLINE, EMBASE, Cochrane Library and CINAHL) was undertaken. Reference lists of retrieved reports were also reviewed. Studies reporting utility single-index measures (preference based) in NeuP were included. Random effects meta-analysis was used to pool EQ-5D index utility estimates across NeuP conditions. The association of utilities and pre-defined factors (NeuP condition, patient age, sex, duration and severity of pain and method of utility scoring) was examined using meta-regression. Twenty-four studies reporting health utility values in patients with NeuP were included in the review. Weighted pooled utility score across the studies varied from a mean of 0.15 for failed back surgery syndrome to 0.61 for post-herpetic neuralgia and diabetic neuropathy. Although there was substantial heterogeneity (P<0.0001) across studies, we found little variation in utility as a function of patient and study characteristics. The single exception was a significant relationship (P<0.0001) between increasing neuropathic pain severity and a reduction in utility. This study confirms the hypothesis that patients with NeuP experience low utilities and therefore low HRQoL. However, the contribution of non-NeuP co-morbidity remains unclear. Neuropathic pain severity emerged as a primary predictor of the negative health impact of NeuP. Copyright 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.