Neuropathic pain: strategies in drug discovery and treatment

Neuropathic pain can be described as pain associated with damage or permanent alteration of the peripheral or central nervous system. In contrast to acute nociceptive pain, the cascade of events that arise following peripheral nerve injury leads to a maintained abnormality in the sensory system, resulting in an abnormal pain phenomenon that can be grossly debilitating. At present, there are very few effective and well-tolerated therapies for neuropathic pain. The development of animal models and constant progress in the understanding of the basic pathophysiology of neuropathic pain has led to multifarious drug targets and treatment options. The most effective agents are use-dependent inhibitors of Na⁺ channels, namely phenytoin, lamotrigine and carbamazepine. Owing to an effect of increase in the serotonin and various other biogenic amine levels on the pain modulating system, various classes of antidepressants including selective serotonin re-uptake inhibitors and selective noradrenaline re-uptake inhibitors are being used clinically. Modulation of Ca²⁺ channels is another useful approach for the treatment of neuropathic pain. In particular, the modulation of N-type Ca²⁺ channels, which are expressed primarily in central and peripheral nervous tissues, has been the subject of greatest interest. In view of the above, this review discusses the various strategies and approaches to novel drug discovery and pharmacotherapy of neuropathic pain syndromes.