Anticonvulsants (antineuropathics) for neuropathic pain syndromes

Our knowledge about the pathogenesis of neuropathic pain has grown significantly during last two decades. Basic research with animal models of neuropathic pain and human clinical trials with neuropathic pain have accumulated solid evidence that a number of pathophysiologic and biochemical changes take place in the nervous system at a peripheral or central level as a result of the insult or disease. Many similarities between the pathophysiologic phenomena observed in some epilepsy models and neuropathic pain models justify the rationale for the use of anticonvulsant drugs in the symptomatic management of neuropathic pain disorders. Carbamazepine (CBZ) was the first representative from this class of drugs to be studied in clinical trials. It has been used for the treatment of neuropathic pain syndromes, in particular, trigeminal neuralgia (TN), for the longest time of any of the drugs in this class. Results from clinical trials support the use of CBZ in the treatment of TN, painful diabetic neuropathy, and postherpetic neuralgia. The use of CBZ was not studied for complex regional pain syndrome, phantom limb pain, and other neuropathic conditions, however. Phenytoin was the first anticonvulsant to be used as an antinociceptive agent, but based on clinical trials, there is no evidence for its efficacy in relieving neuropathic pain. Newer anticonvulsants have marked a new era in the treatment of neuropathic pain, with clinical trials of higher quality standards. Gabapentin (GBP) has most clearly demonstrated an analgesic effect for the treatment of neuropathic pain, specifically for the treatment of painful diabetic neuropathy and postherpetic neuralgia. Gabapentin has a favorable side effects profile, and based on the results of these studies, it should be considered a first-line treatment for neuropathic pain. Gabapentin mechanisms of action are still not thoroughly defined, but GBP is effective in relieving indexes of allodynia and hyperalgesia in animal models. It still remains to be seen whether GBP is as effective in other painful disorders. One small clinical trial with lamotrigine demonstrated improved pain control in TN. Evidence in support of the efficacy of anticonvulsant drugs in the treatment of neuropathic pain continues to evolve, and benefits have been clearly demonstrated in the case of GBP and CBZ. More advances in our understanding of the mechanisms underlying neuropathic pain syndromes should further our opportunities to establish the role of anticonvulsants in the treatment of neuropathic pain.