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In vivo evidence for a role of protein kinase C in peripheral nociceptive processing
Author(s) -
Souza Adriano L S,
Moreira Fabrício A,
Almeida Karine R,
Bertollo Caryne M,
Costa Karina A,
Coelho Márcio M
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704434
Subject(s) - nociception , protein kinase c , hyperalgesia , chelerythrine , licking , allodynia , pharmacology , chemistry , bradykinin , bisindolylmaleimide , medicine , kinase , receptor , biochemistry
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). Intraplantar injection of phorbol‐12,13‐didecanoate (PDD; 0.01, 0.1 or 1 μg), a PKC activator, but not of 4α‐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 μg) also induced mechanical allodynia. In mice, injection of PDD (0.1 or 1 μg) into the dorsum of the hindpaw induced a spontaneous licking behaviour. Intraplantar co‐injection of chelerythrine (10 or 50 μg), a PKC inhibitor, attenuated the thermal hyperalgesia induced by PDD (0.1 μg) in rats. The second phase of the nociceptive response induced by the injection of formaldehyde (0.92%, 20 μl) into the dorsum of mice hindpaws was inhibited by ipsi‐, but not contralateral, pre‐treatment with chelerythrine (1 μg). Intraplantar injection of BK (10 μg) induced mechanical allodynia in rats. Ipsi‐ but not contralateral injection of bisindolylmaleimide I (10 μg), a PKC inhibitor, inhibited BK‐induced mechanical allodynia. 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.British Journal of Pharmacology (2002) 135 , 239–247; doi: 10.1038/sj.bjp.0704434