Evaluation of protective effects of non-selective cannabinoid receptor agonist WIN 55,212-2 against the nitroglycerine-induced acute and chronic animal models of migraine: A mechanistic study

Mohammadi Vosough, E. and Baradaran Rahimi, V. and Masoud, S.A. and Mirkarimi, H.R. and Demneh, M.K. and Abed, A. and Banafshe, H.R. and Askari, V.R. (2019) Evaluation of protective effects of non-selective cannabinoid receptor agonist WIN 55,212-2 against the nitroglycerine-induced acute and chronic animal models of migraine: A mechanistic study. Life Sciences, 232.

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Abstract

Aim: Migraine is a neurological debilitating disorder. Previous studies have shown that cannabinoid receptor agonists have analgesic effects in various models of pain. In this study, therefore, we investigated anti-nociceptive effects of WIN 55,212-2, and the role of either CB1 or CB2 receptors in nitroglycerine (NTG)-induced animal model of migraine. Methods: The present study was conducted on both male and female rats receiving NTG (10 mg/kg, i.p.) to induce acute (single dose of NTG) and chronic (repetitive doses of NTG) models of migraine. Additionally, three groups received WIN 55,212-2 (0.33, 1, 3 mg/kg, i.p.) 45 min before behavioral tests. Additionally, AM251 and AM630 (CB1 and CB2 receptor antagonist, respectively, 1 mg/kg, i.p.) were used to evaluate the possible involvement of CB1 and CB2 receptors during the protective effects of WIN 55,212-2. Key findings: We found that NTG (10 mg/kg, i.p.) in both acute and chronic models increased sensitivity to pain. In acute model, we found that WIN 55,212-2 (almost high doses) decreases the level of pain mainly through CB1 receptor due to CB1 antagonist abrogates its protective effects, however, in formalin test CB2 receptors also had crucial roles in both phases at 3 mg/kg of WIN 55,212-2. In chronic model, WIN 55,212-2 (0.33, 1 and 3 mg/kg) significantly attenuated NTG-induced hyperalgesia through both CB1 and CB2 receptors. Significance: Our data supported the argument that activation of CB1 and CB2 receptors by WIN 55,212-2 may be considered a new medication for migraine, however in lack of each receptor leads to different responses from deletion to the reduction of analgesic effects. © 2019 Elsevier Inc.

Item Type: Article
Additional Information: cited By 1
Uncontrolled Keywords: 2,3 dihydro 5 methyl 3 (morpholinomethyl) 6 (1 naphthoyl)pyrrolo1,2,3 de1,4benzoxazine; cannabinoid 1 receptor; cannabinoid 2 receptor; 2,3 dihydro 5 methyl 3 (morpholinomethyl) 6 (1 naphthoyl)pyrrolo1,2,3 de1,4benzoxazine; benzoxazine derivative; cannabinoid receptor agonist; glyceryl trinitrate; morpholine derivative; naphthalene derivative, animal experiment; animal model; antinociception; Article; chronic pain; controlled study; dose response; drug dose comparison; drug megadose; drug structure; experimental acute pain test; female; formalin test; male; mechanical allodynia; migraine; neuroprotection; nociception; nonhuman; pain intensity; protein function; Radiant heat plantar test; rat; tail flick test; Von Frey filament test; animal; disease model; migraine, Animals; Benzoxazines; Cannabinoid Receptor Agonists; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Male; Migraine Disorders; Morpholines; Naphthalenes; Nitroglycerin; Rats
Subjects: Physiology
Neuroscience
Pharmacology, Toxicology and Pharmaceutics
Divisions: Faculty of Medicine > Basic Sciences > Department of physiology
Depositing User: ART . editor
Date Deposited: 01 Jan 2020 10:52
Last Modified: 01 Jan 2020 10:52
URI: http://eprints.kaums.ac.ir/id/eprint/4453

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