Endothelin ETB receptors inhibit articular nociception and priming induced by carrageenan in the rat knee-joint

The participation of the endothelin system on nociception and priming induced by carrageenan in the knee-joint was investigated. Intra-articular (i.a.) carrageenan (300 μg) caused long-lasting nociceptive effects (i.e., increases in paw elevation time [PET]), which were potentiated by endothelin-1 (dual endothelin ETA/ETB receptor agonist) and inhibited by sarafotoxin S6c (endothelin ETB receptor agonist; both at 30 pmol, i.a., 24 h beforehand). Priming the naive joint with carrageenan augmented nociceptive responses to a second carrageenan challenge, 72 h later. Carrageenan-induced priming, but not nociception, was potentiated by local BQ-788 (10 nmol, i.a., 15 min before priming; endothelin ETB receptor antagonist; N-cis-2,6-dimethylpiperidinocarbonyl-l-γ-methylleucyl-d-1-methoxycarbonyl-tryptophanil-d-norleucine), but BQ-123 (endothelin ETA receptor antagonist; cyclo [d-Asp-Pro-d-Val-Leu]) was ineffective. Sarafotoxin S6c markedly suppressed carrageenan-induced priming to nociception triggered by carrageenan, endothelin-1 or sarafotoxin S6c, and BQ-788 prevented this action. Thus, selective endothelin ETB receptor agonists inhibit carrageenan-induced nociception and priming in the naive joint. This priming effect of carrageenan to nociception evoked by subsequent inflammatory insults is limited by an endothelin ETB receptor-operated mechanism. [Copyright &y& Elsevier]