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

- ET-1 injection into the upper lip induced facial heat hyperalgesia in female rats, which is mediated by ETA and ETB receptors.
- Ablation of peripheral trigeminal C-fibers or local administration of a TRPV1 antagonist prevented heat hyperalgesia induced by ET-1.
- Neutralization of NGF or blockade of TrkA receptors Anti prevented heat hyperalgesia induced by ET-1 and IRL-1620 (a selective ETB agonist).

ObjectivePronociceptive responses to endothelins in the trigeminal system seem to be mediated by ETA and ETB 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 ETA and ETB receptors to this response, as well as the mechanisms underlying heat hyperalgesia induced by ET-1.DesignET-1 (100 pmol/50 μL) was injected into the upper lip and heat hyperalgesia was evaluated for up to 6 h. Facial heat hyperalgesia induced by ET-1 was assessed in rats pre-treated locally with BQ-123 or BQ-788 (selective ETA and ETB receptor antagonists, respectively, 30 nmol/50 μL); BCTC (TRPV1 receptor antagonist; 300 μg/50 μL); anti-NGF (3 μg/50 μL); K252a (TrkA inhibitor, 1 μg/50 μL); or in rats that received intraganglionar resiniferatoxin injection (RTX, 200 ng/10 μL) to promote C-fibers ablation.ResultsET-1 induced facial heat hyperalgesia that persisted up to 6 h 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 3 h. Local pre-treatment with anti-NGF or K252a was effective to prevent ET-1 induced heat hyperalgesia.ConclusionsIn conclusion, ET-1 is able to induce heat hyperagelsia in trigeminal primary afferents of female rats, which is mediated by ETA and ETB receptors. Activation of TRPV1 receptors and NGF-signaling pathways may contribute to heat hyperalgesia induced by ET-1.