The effect of enalapril on pro-inflammatory cytokines in patients with migraine: a double-blind, randomized clinical trial

Background: One of the possible mechanisms of migraine pathophysiology is neuro inflammation in which, according to previous studies, some changes happen in inflammatory factors like interleukins, adhesion molecules or acute phase reactants. Cytokines may have an essential role in the neurovascular inflammation and also in the process of pain especially in migraine patients. On the other hand, one of the mechanisms by which angiotensin converting enzyme inhibitors (ACEIs) work is anti-inflammation. The goal of this study was to evaluate the effect of enalapril as an ACEI drug, on the proinflammatory cytokines (calcitonin gene-related peptide (CGRP), tumor necrosis factor alpha (TNFα)) of migraine patients. Methods: In this randomized double blind placebo-controlled clinical trial, 40 migraine without aura patients (mean age of 34.42±1.82 years) who were referred to neurology clinics of Isfahan University of Medical Sciences, Iran, between June 2011 and July 2012 were recruited. The patients were randomly divided into two groups. 21 patients were treated with 10 mg enalapril daily for two months as the intervention group and they were compared with matched placebo treated group of 19 patients. Serum samples were collected from all of the subjects and TNFα and CGRP levels were measured by means of ELISA (enzyme-linked immunosorbent assay) kits at the beginning of study (before the intervention) and after 2 months of enalapril or placebo treatment. The serum levels were compared in each group and between the groups. SPSS software, version 16 (SPSS Inc., Chicago, IL, USA) was used for statistical analysis. Results: Six males (15%) and 34 females (85%) were enrolled in this study. The mean of migraine history among the subjects was 74.40±7.54 months. Patients' TNFα level decreased significantly in the case group after treatment with enalapril (P=0.001) while there was no significant change in control group (P=0.769). There was no significant difference in the CGRP concentrations in the intervention and control groups (P=0.795, 0.708 respectively). Conclusion: Enalapril may be effective in improvement of inflammatory responses of migraine patients by decreasing the inflammatory factors like TNFα.