Ion channel targets and treatment efficacy in neuropathic pain

Chronic neuropathic pain due to injury or dysfunction of the nervous system remains a formidable treatment challenge in spite of a growing range of medication choices. We review current clinical research supporting the use of ion channel modulators for neuropathic pain states. New modes of local drug delivery, novel Ca2+ channel targets, and increased choices for drugs with activity at Na(+)channels are transforming this longstanding therapeutic strategy. Clinical decision making is increasingly informed by a more nuanced understanding of the role of voltage-gated Na(+)channels (VGSCs) and Ca2+ channels (VGCCs) in the pathophysiology of nerve injury. Although holding great promise for the future, mechanism-based approaches to treatment will require greater understanding of the analgesic mechanisms of drug action and of the relationships between pathophysiologic mechanisms and clinical presentation. Perspective: Treatment options for neuropathic pain targeting ion channels have grown rapidly in the past decade. An evolving body of clinical research supports the widespread use of this longstanding therapeutic strategy. Improved efficacy of ion channel modulators hinges upon further elucidation of the relationship between signs and symptoms of pain and underlying pathophysiology. (c) 2006 by the American Pain Society.