Involvement of endogenous endothelins in thermal and mechanical inflammatory hyperalgesia in mice

Abstract

Endothelin receptors have been involved in inflammatory, neuropathic and tumoral pain. In the case of inflammatory hyperalgesia, some previous papers have pointed towards the involvement of ETB receptors, although the stimulation of ETA receptors seems to participate in the development of the inflammatory reaction. We have studied the effect of ETA and ETB receptor antagonists in the thermal and mechanical hyperalgesia induced in a model of acute (induced by carrageenan) and chronic (induced by complete Freund's adjuvant, CFA) inflammation in mice. The i.pl. administration of the selective ETA antagonist BQ-123 (1-10 nmol) antagonized the thermal hyperalgesia detected by the unilateral hot plate test, observed in both inflammatory models, whereas the i.pl. administration of the ETB selective antagonist BQ-788 (17.7 nmol) failed to modify this. In contrast, both BQ-123 (3-17.7 nmol) and BQ-788 (3-17.7 nmol) antagonized the mechanical hyperalgesia, as assessed by the Randall-Selitto test in carrageenan- and CFA-treated mice. Both BQ-123 and BQ-788 were able to antagonize the mechanical hyperalgesia induced by ET-1 (200 pmol; i.pl.) in the same dose range. Thus, ETA receptors are involved in both thermal and mechanical hyperalgesia whereas ETB receptors are only involved in mechanical hyperalgesia in these inflammatory models. In conclusion, the role of ETB receptors in inflammatory pain is further supported and new insights into the participation of ETA receptors in inflammatory hyperalgesia are given.

Effect of endothelin antagonist (TAK-044) on cerebral ischemic volume, oxidative stress markers and neurobehavioral parameters in the middle cerebral artery occlusion model of stroke in rats

“…Apart from vasodilatory effect, endothelin antagonists also have the anti-inflammatory (Baamonde et al, 2004;Lehmberg et al, 2003;Bajory et al, 2002) and antioxidant activity (Andrasi et al, 2002). These properties of ET antagonist together may be contributing to its protective effect in the MCA occlusion model of acute ischemic stroke.…”

“…Studies have shown that ET antagonists also possess anti-inflammatory property (Baamonde et al, 2004;Lehmberg et al, 2003;Bajory et al, 2002). Inflammation has been implicated as a secondary injury mechanism following ischemic stroke and a variety of experimental models and clinical studies have demonstrated the same.…”

Nociceptive Effect of Subcutaneously Injected Interleukin-12 Is Mediated by Endothelin (ET) Acting on ETBReceptors in Rats

“…In fact, it has also been reported that the antinociception mediated by endothelin via the ET B receptor is opioid-sensitive (Khodorova et al, 2003). However, other investigators have reported that both ET A and ET B mediate nociception in abdominal writhing (Raffa et al, 1996) and carrageenan-induced mechanical hyperalgesia (Baamonde et al, 2004). These apparent discrepancies could be due to differences in experimental nociceptive models, the dose of endothelin, and time intervals of the nociceptive responses, which might detect the hyperalgesia of different sets of primary sensory neurons.…”

Participação da endotelina-1 na sinovite induzida por carragenina na articulação temporomandibular de ratos.

“…Por outro lado, concentrações menores (entre 10 pmols à ! alodinia mecânica (Balonov et al, 2006;Menendez et al, 2003;Piovezan et al, 1998 (Baamonde et al, 2004;Balonov et al, 2006), enquanto a dor evidente é inibida apenas pelo bloqueio do receptor ET A , da mesma forma que ocorre com todas as respostas pró-algésicas envolvendo ET 1 (Baamonde et al, 2004;Davar et al, 1998;De-Melo et al, 1998;;Gokin et al, 2001;Mckelvy et al, 2007;Mujenda et al, 2007;Raffa et al, 1996).…”

“…Khodorova et al (2006) (Baamonde et al, 2004;Davar et al, 1998;De-Melo et al, 1998;Gokin et al, 2001;Mckelvy et al, 2007;Mujenda et al, 2007;Raffa et al, 1996;).…”