Abstract

Abstract Background Calcitonin gene related peptide (CGRP) is known to be the most potent vasodilator of the body, and it promotes migration of inflammatory cells. CGRPβ isoform is located along the enteric nervous system, and CGRPα is mainly present in the central nervous system. CGRPα is known to be the key molecule in migraine, an entity with digestive symptoms. It has been suggested that migraine prevalence is increased in inflammatory bowel disease (IBD). The aim of the study was to assess CGRPα serum levels in patients with newly diagnosed of IBD, stratified by migraine diagnosis, to unravel its potential role in the disease. Methods CGRPα serum concentrations were measured by ELISA (CUSABIO, China) in early morning samples of newly diagnosed patients with IBD. Classification of the disease (ulcerative colitis- UC, Crohn’s disease- CD or unclassified inflammatory bowel disease- U-IBD), demographic data and treatment during sample collection were also collected. To establish a migraine diagnosis, patients were interviewed about prior migraine diagnosis and validated ID-migraine questionnaire was used to diagnose patients with migraine. The results were compared with healthy controls (HC) matched by age and sex. Statistical analysis was performed using SPSS and CGRPα levels were compared with Mann-Whitney and Dunn’s tests. Results Sixty-two patients with newly diagnosed IBD (mean age 47.9±16.3 years, 62.5% females) were matched with 71 HC (mean age 48.2±16.7 years, 64.8% females). Samples were collected between 0 and 249 days after IBD diagnosis was stablished (median 50.5 days, interquartile range 26.75-64.5 days). We included 27 patients with CD, 31 with UC and 4 with U-IBD. Baseline characteristics are shown in table 1. Fifteen female patients met migraine criteria (22.7%). Serum CGRPα levels in patients with IBD were significantly increased (59.7±26.3 pg/mL), compared to HC (43.6±25.3 pg/mL, p<0.0001). CGRPα remained significantly elevated as compared to HC both in IBD patients with migraine (74.8±27.3 pg/mL, p< 0.001) and without migraine (58.6±24.4 pg/mL, p<0.05), though those with migraine were significantly increased as compared to IBD patients without migraine (p<0.05). These results are shown in figures 1 and 2. Conclusion Serum CGRPα levels are increased in patients with IBD, regardless of migraine diagnosis, which could indicate a role of this peptide in the pathophysiology of IBD. These results, and especially the higher levels in IBD patients with migraine, suggest a bidirectional, shared pathophysiology between migraine and IBD, which could be a further example of the clinical relevance of the gut-brain axis. Supported by Instituto de Salud Carlos III (PI20/01358).

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