RT Journal Article
SR Electronic
T1 Protein Kinase C ϵ and γ: Involvement in Formalin-Induced Nociception in Neonatal Rats
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 616
OP 625
DO 10.1124/jpet.103.060350
VO 309
IS 2
A1 Sarah M. Sweitzer
A1 Shirley M. E. Wong
A1 Michael C. Peters
A1 Daria Mochly-Rosen
A1 David C. Yeomans
A1 Joan J. Kendig
YR 2004
UL http://jpet.aspetjournals.org/content/309/2/616.abstract
AB The central nervous system undergoes dynamic changes as it matures. However, until recently, very little was known about the impact of these changes on pain and analgesia. This study tested the hypothesis that the ϵ and γ isozymes of protein kinase C (PKC) contribute to formalin-induced nociception in an age-dependent manner. Expression of ϵ and γ PKC and the contributions of these isozymes in formalin-induced nociception was examined in postnatal day 7, 15, and 21 rats. ϵPKC expression in dorsal root ganglion neurons and γPKC expression in lamina II of the spinal cord increased from the first to the third postnatal week. Coupling immunohistochemical and Western analysis, translocation of ϵPKC followed intraplantar formalin in all ages. In contrast, formalin-induced γPKC translocation was observed only in postnatal day 21 rats. Behaviorally, intrathecal administration of the ϵPKC-specific inhibitor (ϵV1-2) attenuated phase 1 and phase 2 formalin behaviors at all ages. In contrast, intrathecal administration of the γPKC-specific inhibitor (γV5-3) attenuated only phase 2 responses in postnatal day 15 and 21 rats. Functionally, inhibition of ϵPKC decreased capsaicin-stimulated release of glutamate and calcitonin gene-related peptide in spinal cords isolated from postnatal day 7 rats. These results suggest that ϵPKC age independently mediates inflammatory pain produced by intraplantar formalin. In contrast, γPKC contributes to formalin-induced nociception in an age-dependent manner. Identifying the molecular mechanisms responsible for age-specific patterns of nociception is necessary for the rational development of novel therapeutic strategies for treating pediatric pain. The American Society for Pharmacology and Experimental Therapeutics