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NEUROPHARMACOLOGY

Protein Kinase C and : Involvement in Formalin-Induced Nociception in Neonatal Rats

Departments of Anesthesia (S.M.S., S.M.E.W., M.C.P., D.C.Y., J.J.K.) and Molecular Pharmacology (D.M.-R.), Stanford University School of Medicine, Stanford, California

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 and isozymes of protein kinase C (PKC) contribute to formalin-induced nociception in an age-dependent manner. Expression of and PKC and the contributions of these isozymes in formalin-induced nociception was examined in postnatal day 7, 15, and 21 rats. PKC expression in dorsal root ganglion neurons and PKC expression in lamina II of the spinal cord increased from the first to the third postnatal week. Coupling immunohistochemical and Western analysis, translocation of PKC followed intraplantar formalin in all ages. In contrast, formalin-induced PKC translocation was observed only in postnatal day 21 rats. Behaviorally, intrathecal administration of the PKC-specific inhibitor (V1-2) attenuated phase 1 and phase 2 formalin behaviors at all ages. In contrast, intrathecal administration of the PKC-specific inhibitor (V5-3) attenuated only phase 2 responses in postnatal day 15 and 21 rats. Functionally, inhibition of PKC decreased capsaicin-stimulated release of glutamate and calcitonin gene-related peptide in spinal cords isolated from postnatal day 7 rats. These results suggest that PKC age independently mediates inflammatory pain produced by intraplantar formalin. In contrast, PKC 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.

Address correspondence to: Dr. Sarah M. Sweitzer, Department of Pharmacology, Physiology, and Neuroscience, University of South Carolina School of Medicine, Columbia, SC 29208. E-mail: sweitzer{at}gw.med.sc.edu

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