1. Endothelin-B receptor activation triggers an endogenous analgesic cascade at sites of peripheral injury
- Author
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Khodorova, Alla, Navarro, Betsy, Jouaville, Laurence Sophie, Murphy, Jo-Ellen, Rice, Frank L, Mazurkiewicz, Joseph E, Long-Woodward, Denise, Stoffel, Markus, Strichartz, Gary R, Yukhananov, Rus, and Davar, Gudarz
- Abstract
Endothelin-1 (ET-1) is a newly described pain mediator that is involved in the pathogenesis of pain states ranging from trauma to cancer. ET-1 is synthesized by keratinocytes in normal skin and is locally released after cutaneous injury. While it is able to trigger pain through its actions on endothelin-A (ET[sub.A]) receptors of local nociceptors, it can coincidentally produce analgesia through endothelin-B (ET[sub.B]) receptors. Here we map a new endogenous analgesic circuit, in which ET[sub.B] receptor activation induces the release of [beta]-endorphin from keratinocytes and the activation of G-protein-coupled inwardly rectifying potassium channels (GIRKs, also named Kir-3) linked to opioid receptors on nociceptors. These results indicate the existence of an intrinsic feedback mechanism to control peripheral pain in skin, and establish keratinocytes as an ET[sub.B] receptor-operated opioid pool., Author(s): Alla Khodorova [1, 8]; Betsy Navarro [2, 8]; Laurence Sophie Jouaville [1, 3, 8]; Jo-Ellen Murphy [4]; Frank L Rice [5]; Joseph E Mazurkiewicz [5]; Denise Long-Woodward [4]; Markus [...]
- Published
- 2003
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