Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
4347513 | Neuroscience Letters | 2009 | 5 Pages |
Abstract
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 (10Â 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 8Â h after injection. Both effects were also induced by similar injections of capsaicin (10-1000Â pmol), but these responses were shorter lasting than those caused by ET-1. Local pre-treatment with the TRPV1 antagonist capsazepine (30Â nmol, i.pl.) reduced only the thermal hyperalgesia induced by ET-1, but fully suppressed both responses to capsaicin (1000Â pmol). Injection of a sub-threshold dose of ET-1 (0.1Â pmol, i.pl.) prior to capsaicin (1Â pmol, i.pl.) 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, 10Â nmol), but unaffected by BQ-788 (ETB receptors antagonist, 10Â 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.
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Authors
Emerson Marcelo Motta, Juliana Geremias Chichorro, Giles Alexander Rae,