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Involvement of protein kinase C in 5-HT-evoked thermal hyperalgesia and spinal fos protein expression in the rat.

Abstract
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.
AuthorsXuejiao Chen, Feihong Bing, Peifang Dai, Yanguo Hong
JournalPharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 84 Issue 1 Pg. 8-16 (May 2006) ISSN: 0091-3057 [Print] United States
PMID16730785 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Alkaloids
  • Benzophenanthridines
  • Phenanthridines
  • Proto-Oncogene Proteins c-fos
  • Serotonin
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • chelerythrine
  • Protein Kinase C
Topics
  • 8-Hydroxy-2-(di-n-propylamino)tetralin (pharmacology)
  • Alkaloids
  • Animals
  • Behavior, Animal (drug effects)
  • Benzophenanthridines
  • Hyperalgesia (chemically induced)
  • Immunohistochemistry
  • Male
  • Phenanthridines (pharmacology)
  • Protein Kinase C (metabolism)
  • Proto-Oncogene Proteins c-fos (metabolism)
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin (pharmacology)
  • Spine (drug effects, metabolism)

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