Voltage-gated sodium channels in nociception and their potential as targets for new drugs in treatment of chronic neuropathic pain

Voltage-gated sodium channels are important in the pathophysiology of chronic neuropathic pain and as targets for analgesic drugs. This review will cover the molecular structure and signalling roles for this ion channel super-family with a focus on the channels thought to be involved in nociception. We highlight the mode of action of current analgesic drugs and the difficulty of treating chronic inflammatory or neuropathic pain states. The discovery of key channel classes, or familial mutations, associated with chronic pain syndromes has resulted in intensive drug discovery programmes. The quest for selective drugs or toxins which safely and effectively block diseased channels without interfering with normal conduction in the central or peripheral nervous system has been frustratingly difficult. Nevertheless new small molecule drugs or channel selective toxins are in the development pipeline. It remains to be seen whether these will represent a significant development in the safe and effective treatment of chronic pain states.