Nitric oxide-mediated spinal disinhibition contributes to the sensitization of primate spinothalamic tract neurons

This study concentrated on whether an increase in spinal nitric oxide (NO) diminishes inhibition of spinothalamic tract (STT) cells induced by activat ing the periaqueductal gray (PAG) or spinal glycinergic and GABAergic recep tors, thus contributing to the sensitization of STT neurons. A reduction in inhibition of the responses to cutaneous mechanical stimuli induced by FAG stimulation was seen in wide dynamic range (WDR) STT cells located in the deep layers of the dorsal horn when these neurons were sensitized during ad ministration of a NO donor, 3-morpholinosydnonimine (SIN-I), into the dorsa l horn by microdialysis. In contrast, PAG-induced inhibition of the respons es of high-threshold (HT) and superficial WDR STT cells was not significant ly changed by spinal infusion of SIN-1. A reduction in FAG inhibition when STT cells were sensitized after intradermal injection of capsaicin could be nearly completely blocked by pretreatment of the dorsal horn with a NO syn thase inhibitor, 7-nitroindazole, Moreover, spinal inhibition of nociceptiv e activity of deep WDR STT neurons elicited bq iontophoretic release of gly cine and GABA agonists was attenuated by administration of SIN-1. This chan ge paralleled the change in PAG-induced inhibition. However, the inhibition of HT and superficial WDR cells induced by glycine and GABA release did no t show a significant change when SIN-I was administered spinally. Combined with our recent results, these data show that the effectiveness of spinal i nhibition can be reduced by the NO/cGMP pathway. Thus disinhibition may con stitute one mechanism underlying central sensitization.