Experimental Research Article

Korean J Pain 2022; 35(1): 22-32

Published online January 1, 2022 https://doi.org/10.3344/kjp.2022.35.1.22

Copyright © The Korean Pain Society.

The role of basolateral amygdala orexin 1 receptors on the modulation of pain and psychosocial deficits in nitroglycerin-induced migraine model in adult male rats

Khadijeh Askari-Zahabi1 , Mehdi Abbasnejad1 , Razieh Kooshki2 , Maryam Raoof3,4 , Saeed Esmaeili-Mahani1 , Ali Mohammad Pourrahimi5 , Mahnaz Zamyad1

1Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran
2Department of Biology, Faculty of Sciences, Lorestan University, Khorramabad, Iran
3Department of Orofacial Pain and Dysfunction, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
4Endodontology Research Center, Kerman University of Medical Sciences, Kerman, Iran
5Kerman Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

Correspondence to:Ali Mohammad Pourrahimi
Kerman Neuroscience Research Center, Institute of Neuropharmacology, Jehad Blvd, Ebn Sina Avenue, Kerman 76198-13159, Iran
Tel: +983432264196
Fax: +9832264198
E-mail: a1poorrahimi2001@yahoo.com

Handling Editor: Sang Hun Kim

Received: December 21, 2020; Revised: April 22, 2021; Accepted: April 23, 2021

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Background: Migraine headaches have been associated with sensory hyperactivity and anomalies in social/emotional responses. The main objective of this study was to evaluate the potential involvement of orexin 1 receptors (Orx1R) within the basolateral amygdala (BLA) in the modulation of pain and psychosocial dysfunction in a nitroglycerin (NTG)-induced rat model of migraine.
Methods: Adult male Wistar rats were injected with NTG (5 mg/kg, intraperitoneal) every second day over nine days to induce migraine. The experiments were done in the following six groups (6 rats per group): untreated control, NTG, NTG plus vehicle, and NTG groups that were post-treated with intra-BLA microinjection of Orx1R antagonist SB-334867 (10, 20, and 40 nM). Thermal hyperalgesia was assessed using the hot plate and tail-flick tests. Moreover, the elevated plus maze (EPM) and open field (OF) tests were used to assess anxiety-like behaviors. The animals’ sociability was evaluated using the three-chamber social task. The NTG-induced photophobia was assessed using a light-dark box.
Results: We observed no change in NTG-induced thermal hyperalgesia following administration of SB-334867 (10, 20, and 40 nM). However, SB-334867 (20 and 40 nM) aggravated the NTG-induced anxiogenic responses in both the EPM and OF tasks. The NTG-induced social impairment was overpowered by SB-334867 at all doses. Time spent in the dark chamber of light-dark box was significantly increased in rats treated with SB-334867 (20 and 40 nM/rat).
Conclusions: The findings suggest a role for Orx1R within the BLA in control comorbid affective complaints with migraine in rats.

Keywords: Amygdala, Anxiety, Basolateral Nuclear Complex, Hyperalgesia, Migraine Disorders, Nitroglycerin, Orexins, Orexin Receptors, Orexin Receptor Antagonists, Rats.