ABSTRACT
Since the discovery of nitric oxide (NO) as a physiological mediator of vasodilation (1) there has been an explosion in the literature on this ubiquitous mediator. It is an endogenous molecule that is involved in many physiological functions, including those of the cardiovascular, immune, and nervous systems. In the peripheral nervous system, NO is one of the many mediators released by ‘‘nonadrenergic, noncholinergic’’ (NANC) nerve fibers that may mediate certain gastrointestinal, genitourinary, and respiratory functions. The discovery of its synthetic enzyme in the central nervous system (CNS) and evidence that NO can mediate the synthesis of cyclic guanosine monophosphate (cGMP) (2) triggered a search for functional roles of NO in the CNS, where it has since been implicated as a neuromediator of many functions, including learning, memory, and coordination of neuronal activity with local blood flow. Among these nervous system functions, it appears to have a role in nociception, both centrally and peripherally, as investigated largely by Gebhart’s and Ferreira’s laboratories respectively. The very large literature that has subsequently emerged cannot be fully surveyed in this short chapter, but we attempt here to indicate the rather bewildering range of effects on nociceptive processing that NO appears to either mediate or modulate.
