Inflammation-induced up-regulation of protein kinase C gamma immunoreactivity in rat spinal cord correlates with enhanced nociceptive processing

Activation of various second messengers contributes to long-term changes in the excitability of dorsal horn neurons and to persistent pain conditions produced by injury. Here, we compared the time-course of decreased mechanic al nociceptive thresholds and the density of protein kinase C gamma immunor eactivity in the dorsal horn after injections of complete Freund's adjuvant in the plantar surface of the rat hindpaw. Complete Freund's adjuvant sign ificantly increased paw diameter and mechanical sensitivity ipsilateral to the inflammation. The changes peaked one day post-injury, but endured for a t least two weeks. In these rats, we recorded a 75-100% increase in protein kinase C gamma immunoreactivity in the ipsilateral superficial dorsal horn of the L4 and L5 segments at all time-points. Electron microscopy revealed that the up-regulation was associated with a significant translocation of protein kinase C gamma immunoreactivity to the plasma membrane. In double-l abel cytochemical studies, we found that about 20% of the protein kinase C gamma-immunoreactive neurons, which are concentrated in inner lamina II, co ntain glutamate decarboxylase-67 messenger RNA, but none stain for parvalbu min or nitric oxide synthase. These results indicate that persistent changes in protein kinase C gamma im munoreactivity parallel the time-course of mechanical allodynia and suggest that protein kinase C gamma contributes to the maintenance of the allodyni a produced by peripheral inflammation. The minimal expression of protein ki nase C gamma in presumed inhibitory neurons suggests that protein kinase C gamma-mediated regulation of excitatory interneurons underlies the changes in spinal cord activity during persistent nociception. (C) 1998 IBRO. Publi shed by Elsevier Science Ltd.