Chronic stress and migraine: bridging neurobiology and holistic management

Migraine is a prevalent and disabling neurological disorder driven by complex interactions among genetic, neurobiological, and psychosocial factors. This review synthesizes current evidence on migraine pathophysiology, epidemiology, and management, emphasizing the role of stress and integrative treatment strategies. Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis and activation of the trigeminovascular system, including calcitonin gene-related peptide (CGRP) signaling, contribute to central sensitization and pain amplification. Chronic stress both precipitates and perpetuates migraine, reinforcing a bidirectional cycle that increases disease burden and risk of chronification. Current management includes acute and preventive pharmacologic therapies; however, gaps persist due to underutilization of preventive treatments and medication overuse. A multimodal, patient-centered approach integrating pharmacologic, behavioral, and interventional strategies is essential for optimal outcomes. Future directions emphasize integrative care models that address the full biopsychosocial spectrum of migraine to reduce disability and improve quality of life. This narrative review searched PubMed and Google Scholar for English-language trials, meta-analyses, systematic reviews, guidelines, and observational studies published from January 1995 to February 2026 on chronic stress, migraine pathophysiology, and pharmacologic, interventional, behavioral, and integrative treatment. Reference lists of key articles were also hand-searched. No formal quality appraisal or meta-analysis was performed.

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Publication Details

Journal
Pain Management
Published
2026-11-05
DOI
https://doi.org/10.1080/17581869.2026.2756439
Primary Topic
Migraine and Headache Studies
Type
article
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article

Chronic stress and migraine: bridging neurobiology and holistic management

Nebojša Nick Knežević, Clara Nemr, Nicholas Kathrein, Brandon Eichler
Pain Management
Migraine and Headache Studies
article

Chronic stress and migraine: bridging neurobiology and holistic management

Nebojša Nick Knežević, Clara Nemr, Nicholas Kathrein, Brandon Eichler
article en

Abstract

Migraine is a prevalent and disabling neurological disorder driven by complex interactions among genetic, neurobiological, and psychosocial factors. This review synthesizes current evidence on migraine pathophysiology, epidemiology, and management, emphasizing the role of stress and integrative treatment strategies. Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis and activation of the trigeminovascular system, including calcitonin gene-related peptide (CGRP) signaling, contribute to central sensitization and pain amplification. Chronic stress both precipitates and perpetuates migraine, reinforcing a bidirectional cycle that increases disease burden and risk of chronification. Current management includes acute and preventive pharmacologic therapies; however, gaps persist due to underutilization of preventive treatments and medication overuse. A multimodal, patient-centered approach integrating pharmacologic, behavioral, and interventional strategies is essential for optimal outcomes. Future directions emphasize integrative care models that address the full biopsychosocial spectrum of migraine to reduce disability and improve quality of life. This narrative review searched PubMed and Google Scholar for English-language trials, meta-analyses, systematic reviews, guidelines, and observational studies published from January 1995 to February 2026 on chronic stress, migraine pathophysiology, and pharmacologic, interventional, behavioral, and integrative treatment. Reference lists of key articles were also hand-searched. No formal quality appraisal or meta-analysis was performed.

Pain Management
Midwestern University (US), University of Illinois Urbana-Champaign (US), University of Illinois System (US), Advocate Illinois Masonic Medical Center (US)
Openalex Percentile: Top 15%
Migraine and Headache Studies
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Chronic stress and migraine: bridging neurobiology and holistic management — Nebojša Nick Knežević, Clara Nemr, et al. · Pain Management (2026) | TGRS Research Map | TGRS