POSSIBLE ROLE OF PROTEIN-KINASE-C IN THE SENSITIZATION OF PRIMATE SPINOTHALAMIC TRACT NEURONS

The responsiveness of spinal cord nociceptive neurons to innocuous mec hanical stimuli can be increased by the release of excitatory amino ac ids (EAAs) and peptides attributable to an injury-induced barrage of i mpulses. This sensitization of spinal dorsal horn neurons can also res ult from administration of phorbol ester by microdialysis, presumably by direct activation of protein kinase C (PKC). This study was designe d to examine the effects of central sensitization of spinothalamic tra ct (STT) neurons produced by intradermal injection of capsaicin on the descending inhibition driven from the periaqueductal gray (PAG) and t he possible role of PKC in this process in anesthetized monkeys. Sensi tization of responses of STT cells to mechanical stimuli was induced b y intradermal injection of capsaicin. PAG inhibition was significantly attenuated when sensitization of responses to mechanical stimuli occu rred. However, perfusion of the spinal cord with NPC15437 (a selective PKC inhibitor) by microdialysis could prevent the sensitization of th e responses to mechanical stimuli and the reduction in PAG inhibition of these responses induced by capsaicin injection. Results similar to those produced by capsaicin injection were observed when a PKC activat or, phorbol ester (12-O-tetradecanoylphorbol-13 3-acetate), was infuse d within the dorsal horn by microdialysis. An inactive phorbol ester ( 4 alpha-phorbol 12,13-didecanoate) had no effect. These results provid e evidence that the activation of PKC contributes to the development o f central sensitization in dorsal horn neurons produced by chemical st imulation with capsaicin. Attenuation of the effectiveness of PAG inhi bition takes place when the sensitization of dorsal horn cells develop s, and PKC may play a significant role in this process.