1. Proposed receptor-mediated mechanisms of melatonin in nitroglycerin-induced migraine-like hyperalgesic conditions in rats.
- Author
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Kilinc E, Torun IE, Baranoglu Kilinc Y, and Töre F
- Subjects
- Animals, Male, Receptor, Melatonin, MT2 metabolism, Mast Cells metabolism, Mast Cells drug effects, Rats, Meninges metabolism, Meninges drug effects, Tryptamines pharmacology, Receptors, Melatonin metabolism, Receptor, Melatonin, MT1 metabolism, Trigeminal Caudal Nucleus metabolism, Melatonin pharmacology, Nitroglycerin pharmacology, Migraine Disorders metabolism, Migraine Disorders drug therapy, Migraine Disorders chemically induced, Hyperalgesia metabolism, Hyperalgesia chemically induced, Hyperalgesia drug therapy, Calcitonin Gene-Related Peptide metabolism, Rats, Sprague-Dawley, Trigeminal Ganglion metabolism, Trigeminal Ganglion drug effects, Prazosin pharmacology, Proto-Oncogene Proteins c-fos metabolism
- Abstract
Melatonin has a therapeutic effect on migraine, but the mechanisms underlying its antimigraine effect have not been elucidated. This study therefore investigated for the first time the receptor-mediated mechanisms of action of melatonin in nitroglycerin (NTG)- induced migraine-like hyperalgesic conditions in rats. Melatonin, nonselective MT1/MT2 antagonist luzindole, selective MT2 antagonist DH97 or potent MT3 antagonist prazosin, alone or in various combinations, were administered to NTG-induced migraine rats and ex-vivo meningeal preparations. Basal and drug-treated pain behaviors were assessed with the von-Frey test. CGRP levels in the trigeminal ganglia, trigeminal nucleus caudalis (TNC) and ex-vivo superfusate medium, as well as c-fos level in the TNC, were measured by ELISA. Meningeal mast cells were stained with toluidine-blue and examined histologically for their activation and count. Melatonin mitigated mechanical hyperalgesia, and c-fos and CGRP expression in the TNC, CGRP expression in trigeminal ganglia, CGRP release from meningeal afferents, all of which were induced by NTG, and also suppressed NTG-stimulated meningeal mast cell activation. The effects of melatonin were abolished in the presence of luzindole and DH97, respectively. However, prazosin did not reverse the effects of melatonin except for mechanical hyperalgesia. Luzindole and DH97 in combinations with prazosin also canceled the effects of melatonin, respectively, other than CGRP expression in the TNC. Melatonin exerts its anti-hyperalgesic effects through modulation of trigeminal expression and meningeal release of CGRP, and meningeal mast cell activation in experimental migraine-like conditions. The effects of melatonin are mainly mediated by MT2 receptors, without excluding a possible role for MT1., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2025
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