Research Summary: A link between gastrointestinal disorders and migraine: Insights into the gut-brain connection

Headache®: The Journal of Head and Face Pain published “A link between gastrointestinal disorders and migraine: Insights into the gut-brain connection.” This published review resulted from a literature search of PubMed for articles relating to a link between gastrointestinal (GI) disorders and migraine.

The study posed two main questions: 

1. Is there evidence in the literature supporting a brain-gut connection between GI disorders and migraine through shared pathophysiological features?
2. Is there an overlap of symptoms between migraine and GI disorders?  

In addition, the authors of the review wanted headache medicine clinicians to become aware that GI disturbances may adversely affect the absorption and efficacy of orally administered migraine treatments.

Study Results

• Published reports point to a strong physiological link between migraine and GI disorders. Patients with migraine who experience symptoms of nausea, vomiting or abdominal pain may not get relief from their migraine symptoms if prescribed an oral medication for acute treatment.
• The autonomic nervous system is thought to play an important role in the association between migraine and GI dysfunction.  
• The pathophysiology of migraine involves serotonergic signaling, which is especially relevant to the nausea, vomiting and alterations in gastric emptying that can accompany migraine. The gut contains around 95% of the body’s total serotonin, and numerous studies utilizing serotonergic pharmacologic agents have suggested that serotonin may play a role in regulating gastric emptying and symptoms associated with GI dysfunction.
• Calcitonin gene-related peptide (CGRP) has been implicated in the initiation of migraine symptomology, and clinical trials have demonstrated that antagonists to the CGRP pathway can be highly effective in the treatment of migraine. In the gut, high levels of CGRP and associated pain have been reported in patients with functional dyspepsia. In addition, published reports indicate that CGRP can inhibit gastric acid secretion and suppress food intake. Finally, evidence has been presented showing that changes in the gut microbiome can alter CGRP signaling mechanisms.
• In migraine, a phenomenon known as cortical spreading depolarization has been shown to activate pain pathways that originate from the trigeminal nerve fibers, resulting in the release of proinflammatory factors such as CGRP. These same proinflammatory mediators also have been implicated in the pathophysiology of GI disorders.

 Implications for Primary Care Clinicians

• Nausea is a frequent symptom of migraine and may affect a patient’s willingness to take an oral medication during an evolving migraine attack. This topic should be thoroughly explored by the clinician when treating patients with migraine who have associated GI symptoms.
• There is good scientific evidence showing that vomiting and reduced gastric motility can affect the rate and efficiency of drug absorption when high intestinal permeability is present. In patients with migraine who also have GI disorders, pre-treatment with agents that increase gastric motility and stomach emptying, such as metoclopramide, can increase the serum concentrations of oral medications during a migraine attack.
• It has been demonstrated that the efficacy of sumatriptan in treating migraine is increased when combined with metoclopramide.
• With the wider availability of non-oral migraine therapies, these treatments should be considered early in the management of patients with migraine who have associated GI dysfunction.

This summary is part of the First Contact – Headache in Primary Care initiative, an American Headache Society program that provides educational resources to empower healthcare professionals and improve headache and migraine care. We encourage providers in all stages of their careers to visit our homepage to access educational tools to improve patient care.