Role of ETA and ETB endothelin receptors on endothelin-1-induced potentiation of nociceptive and thermal hyperalgesic responses evoked by capsaicin in rats

NEUROSCIENCE LETTERS

卷:457

Article

Motta, Emerson Marcelo¹  Chichorro, Juliana Geremias¹  Rae, Giles Alexander¹ 

[1] Univ Fed Santa Catarina, Ctr Biol Sci, Dept Pharmacol, BR-88049490 Florianopolis, SC, Brazil

关键词: Nociception;    Hyperalgesia;    Capsaicin;    TRPV1 receptor;    Endothelin;   

DOI  :  10.1016/j.neulet.2009.03.055

来源: Elsevier

【 摘 要 】

Increasing evidence indicates that endothelin-1 (ET-1) activates nociceptive neurons and sensitizes them to different noxious stimuli, but involvement of TRPV1-dependent mechanisms in mediation of such effects is not yet fully understood. Here we report that intraplantar (i.pl.) injection of ET-1 (10 pmol) into the hind paw of rats induced overt nociceptive behavior over the first hour, followed by a slowly developing thermal hyperalgesia, lasting from 3 to 8h after injection. Both effects were also induced by similar injections of capsaicin (10-1000 pmol), but these responses were shorter lasting than those caused by ET-1. Local pre-treatment with the TRPV1 antagonist capsazepine (30 nmol, i.pl.)reduced only the thermal hyperalgesia induced by ET-1, but fully suppressed both responses to capsaicin (1000 pmol). Injection of a sub-threshold dose of ET-I (0.1 pmol, i.pl.) prior to capsaicin (1 pmol, Lpl.) markedly sensitized the hind paw to the overt nociceptive and thermal hyperalgesic effects of the later. The potentiation of capsaicin-induced nociception by ET-1 was abolished by prior i.pl. injection of BQ-123 (ETA receptor antagonist, 10 nmol), but unaffected by BQ-788 (ETB receptors antagonist, 10 nmol), whereas the enhancement of capsaicin-induced hyperalgesia by ET-1 was attenuated by both antagonists. Therefore, differently to what has been reported in mice, in rats TRPV1 receptors contribute selectively to thermal hyperalgesia, but not overt nociception, induced by ET-1. Importantly, although ET-1 augments capsaicin-induced overt nociception and thermal hyperalgesia, potentiation of the former relies solely on ETA receptor-mediated signaling mechanisms, whereas both receptors contribute to the latter. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

【 授权许可】

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