title: Chronic ghrelin treatment reduced photophobia and anxiety-like behaviors in nitroglycerin- induced migraine: role of pituitary adenylate cyclase-activating polypeptide.
abstract: Chronic migraine is a debilitating disorder that has a significant impact on patients and society. Nearly all migraineurs frequently reported light sensitivity during a headache attack. Pituitary adenylate cyclase-activating polypeptide (PACAP) plays an important role in the activation of trigeminal system and migraine pain. To identify the effect of chronic ghrelin treatment on endogenous PACAP and associated symptoms of migraine, an experimental chronic migraine model was induced by intermittent intraperitoneal (i.p) injection of nitroglycerin (NTG). Photophobia and anxiety-like behaviors were determined in the modified elevated plus maze on days 2, 4, 6, 8, and 10 and in the light/dark box on days 3, 5, 7, 9, and 11. Blood levels of PACAP and cortisol were assessed by enzyme-linked immunosorbent (ELISA) kits. Chronic injection of NTG evoked photophobia and anxiety-like behaviors and treatment with ghrelin (150 μg/kg) for 11 days effectively attenuated photophobia and anxiety-like behaviors in the both paradigms. We further found that NTG increased the blood levels of PACAP and cortisol, which was significantly reduced by ghrelin treatment. Additionally, staining with Hematoxylin and Eosin (H&E) revealed that ghrelin reduced NTG-induced increase in the number of satellite glial cells in the trigeminal ganglion. Furthermore, for the first time we showed that repeated administrations of NTG increased white blood cell (WBC) counts and mean platelet volume (MPV), and decreased platelet counts. These results indicated that ghrelin decreased migraine associated symptoms possibly through attenuating endogenous PACAP and cortisol levels. Therefore, ghrelin may hold therapeutic potentialities in managing the chronic migraine.
authors.affiliation: Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran.|Student Research Committee of Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Fereshteh
authors.initials: F
authors.lastname: Farajdokht
authors.affiliation: Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Shirin
authors.initials: S
authors.lastname: Babri
authors.affiliation: Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Pouran
authors.initials: P
authors.lastname: Karimi
authors.affiliation: Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Alipour
authors.affiliation: Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Ramin
authors.initials: R
authors.lastname: Bughchechi
authors.affiliation: Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Gisou
authors.identifier: 0000-0002-3732-1663
authors.initials: G
authors.lastname: Mohaddes
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy* / Q000209:etiology; D054439:Ghrelin / Q000627:therapeutic use*; D006854:Hydrocortisone / Q000097:blood; D007958:Leukocyte Count; D008297:Male; D018782:Maze Learning; D008881:Migraine Disorders / Q000188:drug therapy* / Q000209:etiology; D005996:Nitroglycerin / Q000633:toxicity; D020795:Photophobia / Q000188:drug therapy* / Q000209:etiology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000097:blood*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D054439:Ghrelin; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D005996:Nitroglycerin; D006854:Hydrocortisone
keywords: cortisol; elevated plus maze; light/dark box; neuropeptides; satellite cells