Inflammation-induced up-regulation of protein kinase Cgamma 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 mechanical nociceptive thresholds and the density of protein kinase Cgamma immunoreactivity in the dorsal horn after injections of complete Freund's adjuvant in the plantar surface of the rat hindpaw. Complete Freund's adjuvant significantly increased paw diameter and mechanical sensitivity ipsilateral to the inflammation. The changes peaked one day post-injury, but endured for at least two weeks. In these rats, we recorded a 75-100% increase in protein kinase Cgamma 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 Cgamma immunoreactivity to the plasma membrane. In double-label cytochemical studies, we found that about 20% of the protein kinase Cgamma-immunoreactive neurons, which are concentrated in inner lamina II, contain glutamate decarboxylase-67 messenger RNA, but none stain for parvalbumin or nitric oxide synthase. These results indicate that persistent changes in protein kinase Cgamma immunoreactivity parallel the time-course of mechanical allodynia and suggest that protein kinase Cgamma contributes to the maintenance of the allodynia produced by peripheral inflammation. The minimal expression of protein kinase Cgamma in presumed inhibitory neurons suggests that protein kinase Cgamma-mediated regulation of excitatory interneurons underlies the changes in spinal cord activity during persistent nociception.
Martin
W J
WJ
Department of Anatomy, W.M. Keck Foundation Center for Integrative Neuroscience, University of California at San Francisco, 94143, USA.
Liu
H
H
Wang
H
H
Malmberg
A B
AB
Basbaum
A I
AI
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D005620:Freund's Adjuvant; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006614:Hindlimb; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology* / Q000523:psychology; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D009619:Nociceptors / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000201:enzymology* / Q000503:physiopathology*
D007527:Isoenzymes; D005620:Freund's Adjuvant; C087857:protein kinase C gamma; D011493:Protein Kinase C; D005968:Glutamate Decarboxylase