Anticonvulsants for neuropathic pain syndromes - Mechanisms of action and place in therapy

Neuropathic pain, a form of chronic pain caused by injury to or disease of the peripheral or central nervous system, is a formidable therapeutic chall enge to clinicians because it does not respond well to traditional pain the rapies. Our knowledge about the pathogenesis of neuropathic pain has grown significantly over last 2 decades. Basic research with animal and human mod els of neuropathic pain has shown that a number of pathophysiological and b iochemical changes take place in the nervous system as a result of an insul t. This property of the nervous system to adapt morphologically and functio nally to external stimuli is known as neuroplasticity and plays a crucial r ole in the onset and maintenance of pain symptoms. Many similarities betwee n the pathophysiological phenomena observed in some epilepsy models and in neuropathic pain models justify the rational for use of anticonvulsant drug s in the symptomatic management of neuropathic pain disorders. Carbamazepine, the first anticonvulsant studied in clinical trials, probabl y alleviates pain by decreasing conductance in Na+ channels and inhibiting ectopic discharges. Results from clinical trials have been positive in the treatment of trigeminal neuralgia, painful diabetic neuropathy and postherp etic neuralgia. The availability of newer anticonvulsants tested in higher quality clinical trials has marked a new era in the treatment of neuropathic pain. Gabapent in has the most clearly demonstrated analgesic effect for the treatment of neuropathic pain, specifically for treatment of painful diabetic neuropathy and postherpetic neuralgia. Based on the positive results of these studies and its favourable adverse effect profile, gabapentin should be considered the first choice of therapy for neuropathic pain. Evidence for the efficacy of phenytoin as an antinociceptive agent is, at b est, weak to modest. Lamotrigine has good potential to modulate and control neuropathic pain, as shown in 2 controlled clinical trials, although anoth er randomised trial showed no effect. There is potential for phenobarbital, clonazepam, valproic acid, topiramate, pregabalin and tiagabine to have an tihyperalgesic and antinociceptive activities based on result in animal mod els of neuropathic pain, but the efficacy of these drugs in the treatment o f human neuropathic pain has not yet been fully determined in clinical tria ls. The role of anticonvulsant drugs in the treatment of neuropathic pain is ev olving and has been clearly demonstrated with gabapentin and carbamazepine. Further advances in our understanding of the mechanisms underlying neuropa thic pain syndromes and well-designed clinical trials should further the op portunities to establish the role of anticonvulsants in the treatment of ne uropathic pain.