The contribution of spinal card neurokinin-1 receptor signaling to pain

Discovery of the occurrence of neurokinin-1 (NK-1) receptor internalization in response to agonist activation has provided researchers with a new tool for studying tachykinin actions. Using the readily observable end point of NK-1 receptor internalization as an activity marker, this observation has allowed for more detailed study of tachykinin systems in vivo and in vitro. What has this technique taught us about tachykinin function and activity in the spinal cord? Here we discuss recent findings, which shed light on the functional relevance of receptor internalization, the regulation of neuropeptide release from primary afferent nociceptors, and the signaling produced by tachykinins during nociception and injury. The potential consequences of these discoveries for the treatment of pain and understanding of the role of tachykinins in nociception are discussed.