A Case Control Study Demonstrates an Increase in Plasma Amylin Associated with Chronic Migraine

Abstract

Background: Chronic migraine (CM) is generally underdiagnosed, highlighting the need to identify diagnostic biomarkers that will also help better understand migraine chronification. The present study set out to evaluate the interictal concentrations of amylin and calcitonin gene-related peptide (CGRP) in the peripheral blood as potential biomarkers for CM. Methods: This was a prospective, multicenter, case-controlled study, into which patients aged 18–65 years with episodic migraine (EM) or CM and healthy control subjects (HC) were enrolled. Interictal amylin and CGRP levels were assessed in blood samples using enzyme-linked immunosorbent assays. Findings: This study was carried out on 249 subjects (58 with EM and 191 with CM) and on 68 HC. Interictal plasma amylin levels were higher in CM patients (47•1 pg/mL) than in the EM patients (28•84 pg/mL, p<0•0001) and HC (24•74 pg/mL, p<0•0001). Moreover, there was more plasma CGRP (20•01 pg/mL) in CM patients than in HC (11•37 pg/mL, p=0•0016), but not more than in EM patients (18•89 pg/mL, p=0•4369). Applying a cut-off concentration of 39•68 pg/mL plasma amylin, the sensitivity to differentiate CM from healthy controls was 57•6% and the specificity was 88•2%. For CGRP, the sensitivity and specificity to differentiate CM from HC using a CGRP level threshold of 9•43pg/mL, was 74•3% and 60•3% respectively. Variables such as age, analgesic overuse, depression, allodynia, use of preventive medication or a history of migraine with aura, did not influence the plasma concentrations of amylin or CGRP. Interpretation: Interictal plasma amylin levels are higher in patients with CM, consequently this protein may serve as a novel biomarker of CM, and its further study could shed light on the mechanisms involved in the process of migraine chronification. Funding Information: Center for Applied Medical Research (CIMA), University of Navarra. Institute of Health Carlos III. Declaration of Interests: PI and EMV received grants from the Spanish Research Network on Cerebrovascular Diseases (RETICSINVICTUS plus -RD12/0014/0009). CDV and RL received grants from the Institute of Health Carlos III (PI15/01578). The storage and use of human biological samples was in part supported by the Biobank of the Foundation for Applied Medical Research (CIMA, University of Navarra, Pamplona, Spain). PI has received honoraria from Allergan, Novartis, Lilly and Teva Pharmaceuticals for activities unrelated to the work submitted. AMO, IMV and CDV declare that they have no competing interests. MRL has received honoraria from TEVA, Zambon, AbbVie and Bial for activities unrelated to the work submitted. RL has received honoraria from Allergan, Novartis, Lilly and Teva Pharmaceuticals for activities unrelated to the work submitted. Ethical Approval Statement: The study was approved by the local research Ethics Committee following the standards for medical research in humans recommended in the Helsinki Declaration. All participants provided their informed consent prior to their enrollment on the study.