Regulation of nociceptive transduction and transmission by nitric oxide.

The potential involvement of nitric oxide (NO), a diffusible gaseous signaling messenger, in nociceptive transduction and transmission has been extensively investigated. However, there is no consistent and convincing evidence supporting the pronociceptive action of NO at the physiological concentration, and the discrepancies are possibly due to the nonspecificity of nitric oxide synthase inhibitors and different concentrations of NO donors used in various studies. At the spinal cord level, NO predominantly reduces synaptic transmission by inhibiting the activity of NMDA receptors and glutamate release from primary afferent terminals through S-nitrosylation of voltage-activated calcium channels. NO also promotes synaptic glycine release from inhibitory interneurons through the cyclic guanosine monophosphate/protein kinase G signaling pathway. Thus, NO probably functions as a negative feedback regulator to reduce nociceptive transmission in the spinal dorsal horn during painful conditions.