Characterization of opioidergic mechanisms related to the anti-migraine effect of vagus nerve stimulation.

Characterization of opioidergic mechanisms related to the anti-migraine effect of vagus nerve stimulation. Neuropharmacology. 2021 Jan 11;:108375 Authors: Hu B, Akerman S, Goadsby PJ Abstract Vagus nerve stimulation (VNS) is a promising neuromodulation approach used in the treatment of migraine, whose therapeutic mechanism is largely unknown. Previous studies suggest that VNS's anti-nociceptive effects may, in part, involved engaging opioidergic mechanisms. We used a validated preclinical model of head pain, with good translational outcomes in migraine, acute intracranial-dural stimulation, and has responded to invasive VNS. We tested the effects of μ (MOR), δ (DOR) and κ (KOR) opioid receptor agonists in this model, and subsequently the effects of opioid receptor antagonists against VNS-mediated neuronal inhibition. MOR, DOR, and KOR agonists all inhibited dural-evoked trigeminocervical neuronal responses. Both DOR and KOR agonists also inhibited ongoing spontaneous firing of dural responsive neurons. Both DOR and KOR agonists were more efficacious than the MOR agonist in this model. We confirm the inhibitory effect of invasive VNS and demonstrate that this effect was prevented by a broad-spectrum opioid receptor antagonist, and by a highly selective DOR antagonist. Our data confirm the role of MOR in dural-trigeminovascular neurotransmission and additionally provide evidence of a role of both DOR and KOR in dural-nociceptive tra...
Source: Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Neuropharmacology Source Type: research