What is the potential of studying receptor expression on nociceptors?

Abstract

Since the early eighties we have witnessed a surge of major discoveries about mechanisms of a unique plasticity in the central nervous system (CNS) that play an important role in the generation of ongoing pain and hyperalgesia [17]. One spectacular example triggered by short periods of noci­ ceptive activity is the increased efficiency of synaptic transmission at pain-relevant neurons in the dorsal horn of the spinal cord [6,12]. These findings of central hyperexcitability have provided a great advance in our conceptual framework for the explanation of erstwhile enigmatic clinical symptoms such as touch-evoked pain (allodynia). Alterations of the CNS circuitry are also implicated in the consolidation of painful conditions that may persist, perhaps indefinitely, in some situations even in the absence of excitation of nociceptors. Al­ though it has been recognized for some time that changes in the receptive properties of nociceptors are the basis of some forms of hyperalgesia notably to heat [13], the impressive advances in the understanding of CNS plasticity have diverted attention from the periph­ eral events of nociception. It is therefore timely that the article by Carlton and Coggeshall refocuses on the peripheral aspects of nociception. In fact, several lines of evidence now show that changes in the excitability of primary nociceptive afferents may be the single most important factor in the generation and maintenance of acute inflammatory or chronic neuropathic pain in hu­ mans. Thus, local anesthetic blocks of affected nerves or tissues, differential nerve blocks, detailed psychophysi­ cal investigations, and intraneural recording and stimula­ tion experiments using microneurography all converge