A Link Between Gastrointestinal Disorders and Migraine: Insights Into the Gut–Brain Connection

Sheena K. Aurora MD; Stephen B. Shrewsbury MB, ChB; Sutapa Ray PhD; Nada Hindiyeh MD; Linda Nguyen MD

Disclosures

Headache. 2021;61(4):576-589. 

In This Article

Abstract and Introduction

Abstract

Background: Migraine is a complex, multifaceted, and disabling headache disease that is often complicated by gastrointestinal (GI) conditions, such as gastroparesis, functional dyspepsia, and cyclic vomiting syndrome (CVS). Functional dyspepsia and CVS are part of a spectrum of disorders newly classified as disorders of gut–brain interaction (DGBI). Gastroparesis and functional dyspepsia are both associated with delayed gastric emptying, while nausea and vomiting are prominent in CVS, which are also symptoms that commonly occur with migraine attacks. Furthermore, these gastric disorders are comorbidities frequently reported by patients with migraine. While very few studies assessing GI disorders in patients with migraine have been performed, they do demonstrate a physiological link between these conditions.

Objective: To summarize the available studies supporting a link between GI comorbidities and migraine, including historical and current scientific evidence, as well as provide evidence that symptoms of GI disorders are also observed outside of migraine attacks during the interictal period. Additionally, the importance of route of administration and formulation of migraine therapies for patients with GI symptoms will be discussed.

Methods: A literature search of PubMed for articles relating to the relationship between the gut and the brain with no restriction on the publication year was performed. Studies providing scientific support for associations of gastroparesis, functional dyspepsia, and CVS with migraine and the impact these associations may have on migraine treatment were the primary focus. This is a narrative review of identified studies.

Results: Although the association between migraine and GI disorders has received very little attention in the literature, the existing evidence suggests that they may share a common etiology. In particular, the relationship between migraine, gastric motility, and vomiting has important clinical implications in the treatment of migraine, as delayed gastric emptying and vomiting may affect oral dosing compliance, and thus, the absorption and efficacy of oral migraine treatments.

Conclusions: There is evidence of a link between migraine and GI comorbidities, including those under the DGBI classification. Many patients do not find adequate relief with oral migraine therapies, which further necessitates increased recognition of GI disorders in patients with migraine by the headache community.

Introduction

Migraine is defined by the International Classification of Headache Disorders (3rd edition) as a common, disabling primary headache disorder.[1] According to the Global Burden of Disease Study in 2016, migraine was the sixth most prevalent disorder, afflicted ~1 billion individuals, and was more predominant in women (18.9%) compared to men (9.8%) globally.[2] Migraine is defined as a recurrent headache disorder with moderate or severe headache attacks that can last for 4–72 h and are accompanied by nausea and/or photophobia and phonophobia.[1] In particular, the nausea that accompanies migraine strongly contributes to the burden and disability associated with migraine.[3] The American Migraine Prevalence and Prevention study conducted in 2009 revealed that patients with migraine who experienced high-frequency nausea had significantly higher odds of occupational disability or taking medical leave, and increased headache pain severity and impact.[3] In addition to nausea, other gastrointestinal (GI) symptoms may be present with migraine and include vomiting, diarrhea, reflux, and constipation.[4,5] A large survey in the United States completed by 29,727 participants reported that 73% and 29% of patients with migraine experienced nausea and vomiting, respectively.[5] In a large analysis of women with migraine, nausea and vomiting were reported by 61.6% of those with migraine with aura and 66.0% without aura.[6] Furthermore, a variety of GI conditions have been associated with migraine, such as inflammatory bowel disease, celiac disease, irritable bowel syndrome (IBS), Helicobacter pylori infection, cyclic vomiting syndrome (CVS), functional dyspepsia, and gastroparesis.[7–13] The Rome Foundation recently introduced the term, disorders of gut–brain interaction (DGBI), which is defined as "a group of disorders classified by GI symptoms related to any combination of motility disturbances, visceral hypersensitivity, altered mucosal and immune function, gut microbiota, and/or central nervous system (CNS) processing."[14] The Rome Foundation is an independent not-for-profit organization that provides support for science-based activities to assist in DGBI diagnosis and treatment.[15] Functional dyspepsia and CVS are included under the DGBI classification, thus, suggesting that an interaction between the brain and gut exists in these common disorders.[14] There is significant overlap between idiopathic gastroparesis and functional dyspepsia such that both are associated with delayed gastric emptying in the absence of a mechanical obstruction, as well as impaired fundic accommodation and gastric hypersensitivity in functional dyspepsia,[16,17] while episodic nausea, vomiting, and abdominal pain are present in CVS.[18] In our recently completed Phase 3 STOP 301 study,[19] 38.4% of our patients (N = 354) had comorbid GI disorders at study entry. Gastroesophageal reflux disease was the most prevalent (20.3%), followed by IBS (5.6%), constipation (4.0%), and dyspepsia (3.1%). There is evidence of an association between migraine and GI disorders in the literature. In this paper, we will review the historical and current state of scientific evidence that exists for a relationship between migraine and GI comorbidities, and how their association may impact migraine treatment.

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