Involvement of protein kinase C in 5-HT-evoked thermal hyperalgesia and spinal fos protein expression in the rat.
The present study was designed to characterize nociceptive response induced by 5-hydroxytryptamine (5-HT) and to investigate effects of inhibition of protein kinase C (PKC) in the periphery on noxious stimulus-evoked activity of the secondary neurons in the spinal cord. Subcutaneous injection of 5-HT (50 microg) and alpha-methylserotonin (alpha-m-5-HT, 5-HT2A receptor agonist, 50 microg) into the unilateral hindpaw evoked significant decreases in paw withdrawal latency (PWL). The 5-HT-induced hyperalgesia was abolished by ketanserin (5-HT2A antagonist, 10 microg, intraplantarly or i.pl.), but not by WAY100635 (5-HT1A antagonist, 100 microg, i.pl.). 5-HT and alpha-m-5-HT also evoked numerous expressions of c-Fos-like immunoreactivity (c-fos-LI) in the ipsilateral dorsal horn (predominantly laminae I-II) of the lumbar spinal cord. However, treatment with 8-OH-DPAT (5-HT1A receptor agonist, 100 microg, i.pl.) elicited only moderate thermal hyperalgesia and very limited expression of spinal c-fos-LI. Intraplantar chelerythrine (2, 6 or 10 microg), a PKC inhibitor, dose-dependently attenuated the hyperalgesia evoked by alpha-m-5-HT. Chelerythrine (10 microg, i.pl.) also completely prevented the development of hyperalgesia evoked by 5-HT but not by 8-OH-DPAT. Furthermore, pretreatment with chelerythrine significantly inhibited the expressions of c-fos-LI evoked by alpha-m-5-HT in laminae I-VI and by 5-HT in laminae I-II. These results demonstrate that PKC activation was involved in the development of nociceptive responses elicited by 5-HT and activation of peripheral 5-HT2A, but not 5-HT1A, receptors. The study also provides evidence at a cellular level that inhibition of PKC in the periphery suppresses the 5-HT-evoked neuronal activity in the central nervous system.
Chen
Xuejiao
X
Department of Anatomy and Physiology, College of Life Sciences, Fujian Normal University, Fuzhou, Fujian, 350000, People's Republic of China.
Bing
Feihong
F
Dai
Peifang
P
Hong
Yanguo
Y
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000470:Alkaloids; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D053119:Benzophenanthridines; D006930:Hyperalgesia / Q000139:chemically induced*; D007150:Immunohistochemistry; D008297:Male; D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology*; D013131:Spine / Q000187:drug effects* / Q000378:metabolism
D000470:Alkaloids; D053119:Benzophenanthridines; D010617:Phenanthridines; D016760:Proto-Oncogene Proteins c-fos; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C016299:chelerythrine; D011493:Protein Kinase C