# Beyond the Headache: Autonomic Reflex Dysfunction and Sensory Hypersensitivity Contribute to Orthostatic Intolerance in Migraine

**Authors:** Bridget R Mueller, Maya Campbell, Jihan Grant, Jasmin Jean, Marianna Vinokur, Michael Kaplan, Daniel Clauw, Jessica Robinson-Papp

PMC · DOI: 10.21203/rs.3.rs-6847469/v1 · 2025-06-16

## TL;DR

The study shows that migraine patients often experience orthostatic intolerance due to autonomic dysfunction and heightened sensory sensitivity.

## Contribution

The paper identifies two distinct mechanisms for orthostatic intolerance in migraine patients: cardiovascular and sensory hypersensitivity.

## Key findings

- 83% of migraine patients experienced orthostatic intolerance during tilt testing.
- POTS was the most common cause of abnormal cardiovascular responses to tilt.
- Sensory hypersensitivity was linked to higher fibromyalgia scores and overlapping pain conditions.

## Abstract

We sought to determine: 1.) the relationship between headache frequency and autonomic reflexes, and 2.) mechanisms underlying orthostatic intolerance (OI) in patients with migraine.

Adults with migraine (N = 30) underwent autonomic function tests summarized as the Composite Autonomic Severity Score (CASS) and vagal/adrenergic baroreflex sensitivity (BRS-V/A). Postural Orthostatic Tachycardia Syndrome (POTS) and orthostatic hypotension/hypertension were diagnosed during tilt table testing. A cold pressor test (CPT) evaluated sympathetic vasomotor function. Participants completed the Migraine Disability Assessment (MIDAS), the 2011 Fibromyalgia (FM) Survey Criteria, chronic overlapping pain condition (COPC) screener, and Compass-31.

Monthly headache days correlated with CASS (p = 0.001), BRS-V (p < 0.001), and the systolic blood pressure response to CPT (p = 0.003) in the expected direction with increasing ANS reflex dysfunction correlating to increasing number of headache days. During tilt testing, OI was prevalent (25/30; 83%) and reported by all patients with chronic migraine. An abnormal cardiovascular response to tilt was present in the majority (63%) of which POTS was the most common etiology (56.2%). Patients reporting OI during tilt table testing despite a normal cardiovascular response (33%) had higher FM scores (15.8 ± 3.6 vs. 7.5 ± 4.6; p < 0.01) and a greater prevalence of non-headache COPCs (88.8% versus 20.0%, p = 0.02), compared to participants who were asymptomatic during tilt.

There are two etiologies of OI in patients with migraine: 1.) an abnormal cardiovascular response to tilt (concordant OI) and, 2.) sensory hypersensitivity (discordant OI).

## Linked entities

- **Diseases:** migraine (MONDO:0005277), Postural Orthostatic Tachycardia Syndrome (MONDO:0011479), fibromyalgia (MONDO:0005546)

## Full-text entities

- **Diseases:** Headache (MESH:D006261), hypertension (MESH:D006973), Sensory Hypersensitivity (MESH:D004342), Autonomic Reflex Dysfunction (MESH:D001342), COPC (MESH:D059350), orthostatic hypotension (MESH:D007024), FM (MESH:D005356), POTS (MESH:D054972), Migraine (MESH:D008881), OI (MESH:D054971)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12204353/full.md

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Source: https://tomesphere.com/paper/PMC12204353