INVOLVEMENT OF CGMP IN NOCICEPTIVE PROCESSING BY AND SENSITIZATION OFSPINOTHALAMIC NEURONS IN PRIMATES

Central sensitization of spinothalamic tract (STT) neurons in anesthet ized monkeys after intradermal injection of capsaicin depends in part on disinhibition. Protein kinase C is suggested to participate in this process. The present study shows that the nitric oxide-cGMP (NO-cGMP) signal transduction system also contributes to sensitization of wide dynamic range (WDR) STT neurons located in the deep dorsal horn. The N O-cGMP system was activated by microdialysis administration into the d orsal horn of 8-bromo-cGMP, an analog of cGMP. Sensitization of STT ce lls by 8-bromo-cGMP increased the responses of deep WDR STT cells to b oth weak and strong mechanical stimulation of the skin and simultaneou sly attenuated the inhibition of the same neurons produced by stimulat ion in the periaqueductal gray (PAG). In contrast, WDR STT cells in th e superficial dorsal horn and high-threshold (HT) STT cells in superfi cial or deep layers showed reduced responses to mechanical stimulation of the skin after infusion of 8-bromo-cGMP, and FAG inhibition of the se neurons was unaffected. Sensitization of STT cells and the attenuat ion of FAG inhibition induced by intradermal injection of capsaicin we re prevented by preteatment of the dorsal horn with a guanylate cyclas e inhibitor, 1 H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one. The results support the hypothesis that activation of the NO-cGMP signal transduc tion system contributes to the sensitization of WDR STT neurons in the deep dorsal horn and helps explain why intradermal capsaicin injectio ns often fail to sensitize superficial and HT STT cells. The results a lso support the idea that sensitization of STT cells is produced in pa rt by disinhibition.