In vivo evidence for a role of protein kinase C in peripheral nociceptive processing.

Abstract:

:1. The present study was designed to characterize the nociceptive response induced by protein kinase C (PKC) peripheral activation and to investigate if this biochemical event is important for the nociceptive response induced by formaldehyde, and bradykinin (BK). 2. Intraplantar injection of phorbol-12,13-didecanoate (PDD; 0.01, 0.1 or 1 microg), a PKC activator, but not of 4 alpha-PDD (inactive analogue), dose-dependently induced thermal hyperalgesia in rats. This response was not observed at the contralateral hindpaw. Intraplantar injection of PDD (0.01, 0.1 or 1 microg) also induced mechanical allodynia. In mice, injection of PDD (0.1 or 1 microg) into the dorsum of the hindpaw induced a spontaneous licking behaviour. 3. Intraplantar co-injection of chelerythrine (10 or 50 microg), a PKC inhibitor, attenuated the thermal hyperalgesia induced by PDD (0.1 microg) in rats. 4. The second phase of the nociceptive response induced by the injection of formaldehyde (0.92%, 20 microl) into the dorsum of mice hindpaws was inhibited by ipsi-, but not contralateral, pre-treatment with chelerythrine (1 microg). 5. Intraplantar injection of BK (10 microg) induced mechanical allodynia in rats. Ipsi- but not contralateral injection of bisindolylmaleimide I (10 microg), a PKC inhibitor, inhibited BK-induced mechanical allodynia. 6. In conclusion, this study demonstrates that PKC activation at peripheral tissues leads to the development of spontaneous nociceptive response, thermal hyperalgesia and mechanical allodynia. Most importantly, it also gives in vivo evidence that peripheral PKC activation is essential for the full establishment of the nociceptive response induced by two different inflammatory stimuli.

journal_name

Br J Pharmacol

authors

Souza AL,Moreira FA,Almeida KR,Bertollo CM,Costa KA,Coelho MM

doi

10.1038/sj.bjp.0704434

subject

Has Abstract

pub_date

2002-01-01 00:00:00

pages

239-47

issue

1

eissn

0007-1188

issn

1476-5381

journal_volume

135

pub_type

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