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

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.

Keywords: cyclic vomiting syndrome; disorders of gut-brain interaction; functional dyspepsia; gastric motility; gastroparesis; migraine.

FIGURE 1

A brain–gut connection between migraine and gastric disorders. There is evidence in the literature supporting a brain‐gut connection. ²¹ This review further corroborates this association by providing evidence of shared pathophysiological features, such as alterations in serotonergic signaling ³⁵ , ³⁶ , ³⁷ , ³⁸ , ³⁹ , ⁴⁰ , ⁴¹ , ⁴² , ⁴³ and autonomic dysfunction, ²⁰ , ²² , ²³ , ²⁴ , ²⁶ , ²⁷ , ²⁸ , ³⁰ , ³¹ and overlapping symptomatology between migraine, ¹ , ⁵³ and GI disorders including gastroparesis, functional dyspepsia, and cyclic vomiting syndrome, often presenting as comorbidities in either condition ⁷ , ¹⁰ , ¹¹ , ⁵⁴ , ⁵⁵ , ⁵⁶ , ⁵⁷ , ⁵⁸

FIGURE 2

Proposed mechanisms explaining the relationship between migraine and gastric disorders. ²¹ , ¹³¹ A bidirectional relationship exists between migraine and gastric disorders, which is influenced by autonomic dysfunction; specifically, altered sympathetic and parasympathetic activity and changes in the gut microbiota profile, which are mediated by various cytokines, hormones, and neurotransmitters. ²¹ In migraine, cortical spreading depression (CSD) activates pain pathways that originate from the parasympathetic trigeminal nerve fibers and results in the release of calcitonin gene‐related peptide (CGRP) and proinflammatory mediators, which are implicated in both migraine and gastrointestinal (GI) disorder pathophysiology. ²² , ¹²⁴ In gastric disorders, it is suggested that stress induced by physical and psychological factors causes the release of corticotrophin‐releasing hormone (CRH), which leads to alterations in gut microbiota and intestinal permeability, the release of proinflammatory mediators, and the inhibition of acetylcholine release, resulting in GI dysfunction. Another major factor contributing to this relationship is an alteration in serotonergic signaling, which can activate the TGV system involved in the initiation of a migraine attack and lead to the development of symptoms of gastric disorders including nausea, emesis, and delayed gastric emptying by altering GI reflex pathways or activating GI serotonin receptors. ²¹ , ⁶² Abbreviations: 5‐HT, 5‐hydroxytryptamine; ACh, acetylcholine; DMV, dorsal motor nucleus of the vagus; TGV, trigeminovascular; TNC, trigeminal nucleus caudalis