Sodium Channel Modulation in the Perception and Management of Pain

Abstract

Sodium channels play a pivotal role in maintaining homeostasis and proper intracellular ion concentrations that are vital to all living cells for function and survival. In excitable tissues such as neurons and heart cells, sodium channels are responsible for establishing and maintaining the transmembrane electrochemical gradient, which is critical for intercellular communication and for the transduction, generation, modulation, and transmission of impulses that underlie normal physiologic function, the perception of stimuli, and the execution of appropriate behavioral responses. Injury and disease often affect changes in the channel density and subtype distribution present in cellular membranes, thereby upsetting the critical electrochemical balance necessary for normal functioning. When such changes affect the systems that process noxious stimulation and are acute and transient, they are beneficial. The pain that is perceived alerts us to current or impending injury and aids in vigilance during wound healing. But when the changes are persistent, the painful signals are no longer protective but, instead, become unrelenting and destructive to the quality of life. Because changes in sodium channel quantity and distribution play such a central role in the perception of pain and the development and maintenance of nociceptive chronicity, significant effort has been expended on discovering ways to affect sodium channel expression and function that might be effective in preventing or managing many painful conditions. The implications of modifying sodium channel expression and function for future therapeutic benefit are the subject of this review. Key Words: Acute pain, chronic pain, sodium channels