ePoster

Effects of NOP receptor agonist and novel mixed NOP/mu opioid receptor agonist on migraine-like symptoms in mice

Diana Pietrzak, Akanksha Mudgal, Robert Kostecki, Akihiko Ozawa, Lawrence Toll, Katarzyna Targowska-Duda
FENS Forum 2024(2024)
Messe Wien Exhibition & Congress Center, Vienna, Austria

Conference

FENS Forum 2024

Messe Wien Exhibition & Congress Center, Vienna, Austria

Resources

Authors & Affiliations

Diana Pietrzak, Akanksha Mudgal, Robert Kostecki, Akihiko Ozawa, Lawrence Toll, Katarzyna Targowska-Duda

Abstract

Migraine is a neurological disorder manifested by throbbing pain, allodynia, as well as light sensitivity (photophobia). Despite continuing research, the pathogenesis of the disease is not precisely understood. Structures implicated in migraine formation, including the trigeminal ganglia and trigeminal nucleus caudalis, exhibit a particularly high expression of Nociceptin Opioid (NOP) receptors. The aim of the study was to compare the effect of selective and non-selective NOP receptor agonists on acute migraine symptoms induced by systemic administration of nitroglicerin (NTG). NTG induces migraine-like symptoms, including mechanical hypersensitivity in head and paw, but also photophobia in mice. The von Frey test was used to investigate the effects of NOP receptor agonists on head and paw sensitivity, while the light/dark box test was used to investigate NTG-induced photophobia. Because of Ro 64-6198's anxiolytic activity, the elevated plus maze (EPM) test was performed to rule out any potential anxiety-related influence of the studied NOP agonist on the NTG-induced effects. We found that selective agonist of NOP receptor Ro 64-6198 effectively ameliorates NTG-induced allodynia in mice. The effect after Ro 64-6198 administration was fully inhibited by the NOP receptor antagonist SB-612111. Ro 64-6198 also abolished NTG-induced photophobia, which was not due to its anxiolytic effect, as confirmed by the EPM test. A full agonist for both NOP receptor and mu opioid receptor blocks head and paw sensitivity in male and female mice. The administration of SB-612111 slightly decreased the analgesic effect. These findings suggest the involvement of NOP receptor in migraine pain amelioration.

Unique ID: fens-24/effects-receptor-agonist-novel-mixed-cca248c6