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.