The effect of melatonin on gene expression of calcitonin gene-related peptide and some proinflammatory mediators in patients with pure menstrual migraine

Abstract

The neuropeptide calcitonin gene-related peptide (CGRP), a potent vasoactive and a marker of trigeminal inflammation, has been considered as an important mediator in various types of migraine such as pure menstrual migraine. Earlier studies have shown that CGRP can modulate the synthesis and release of other inflammatory factor including nitric oxide (NO) and interleukin-1beta (IL-1β) from trigeminal ganglion glial cells. Exogenous melatonin protects the tissues from inflammatory damages. The goal of this study was to determine the anti-inflammatory effects of melatonin on the CGRP expression, inducible nitric oxide synthase (iNOS) activity, NO, and IL-1β release in cultured peripheral blood mononuclear cells (PBMCs) from pure menstrual migraine patients and healthy subjects. This study was performed on 12 pure menstrual migraine patients and 12 age-and sex-matched healthy subjects. PBMCs were isolated and treated with melatonin for 12 h at pharmacological dose. Gene expression was evaluated by real-time PCR. CGRP and IL-1β proteins in culture supernatant were determined by ELISA method. iNOS activity in PBMCs was determined by colorimetric assays. Total nitrite as an indicator of NO concentrations in the culture supernatants was measured using Griess method. We found that melatonin treatment significantly decreases mRNA expression of CGRP release, NO production, and iNOS activity in the patient groups. Taken together, it appears that melatonin reduces inflammation through decreasing CGRP level and iNOS activity in the patients with migraine; however, further studies are needed in this regard.

Preliminary Evidence that Melatonin Is not a Biomarker in Children and Adolescents With Episodic Migraine

“…Other work indicates that the addition of melatonin to cultured human blood cells reduces the neuropeptide calcitonin gene‐related peptide (CGRP) mRNA and nitric oxide (NO) nitrate levels in the blood . Despite the caveat that melatonin was added to cultured human peripheral blood mononuclear cells, this finding indicates that melatonin may have a protective effect against migraine.…”

Current understanding of pineal gland structure and function in headache

“…Melatonin has been shown to decrease CGRP in other studies. Melatonin injection in vitro decreased CGRP-mediated activity regulating cerebral arterial tone in the middle cerebral arteries of rats (58). In a neuropathic pain model in mice, melatonin inhibited the activation of peptidergic neurons and neuro-inflammation in the dorsal root ganglia neurons by down-regulating CGRP (59).…”

Major depression subtypes are differentially associated with migraine subtype, prevalence and severity

“…Melatonin, a hormone primarily involved in the regulation of the sleep-wake cycle, might interact with calcitonin gene-related peptide (CGRP) effects. Specifically, melatonin was shown to inhibit CGRPinduced vasodilation of cerebral arteries in rats (29), as well as to downregulate CGRP mRNA levels in human peripheral blood mononuclear cells from migraine patients (30). CGRP levels are increased in migraine patients both during attacks and in the interictal state, compared to controls (31), and CGRP has been suggested to regulate appetite and energy intake (32).…”