Mechanisms involved in facial heat hyperalgesia induced by endothelin-1 in female rats.

OBJECTIVE

Pronociceptive responses to endothelins in the trigeminal system seem to be mediated by ET and ET receptors, which have been shown to be expressed in neurons of the trigeminal ganglion of humans and rats. The present study aimed to evaluate the ability of endothelin-1 (ET-1) to induce facial heat hyperalgesia in female rats, the contribution of ET and ET receptors to this response, as well as the mechanisms underlying heat hyperalgesia induced by ET-1.

DESIGN

ET-1 (100pmol/50μL) was injected into the upper lip and heat hyperalgesia was evaluated for up to 6h. Facial heat hyperalgesia induced by ET-1 was assessed in rats pre-treated locally with BQ-123 or BQ-788 (selective ET and ET receptor antagonists, respectively, 30nmol/50μL); BCTC (TRPV1 receptor antagonist; 300μg/50μL); anti-NGF (3μg/50μL); K252a (TrkA inhibitor, 1μg/50μL); or in rats that received intraganglionar resiniferatoxin injection (RTX, 200ng/10μL) to promote C-fibers ablation.

RESULTS

ET-1 induced facial heat hyperalgesia that persisted up to 6h and was prevented by BQ-123, BQ-788 or by intraganglionar RTX injection. Likewise, local pre-treatment with BCTC abolished ET-1 induced facial heat hyperalgesia up to 3h. Local pre-treatment with anti-NGF or K252a was effective to prevent ET-1 induced heat hyperalgesia.

CONCLUSIONS

In conclusion, ET-1 is able to induce heat hyperagelsia in trigeminal primary afferents of female rats, which is mediated by ET and ET receptors. Activation of TRPV1 receptors and NGF-signaling pathways may contribute to heat hyperalgesia induced by ET-1.