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The comorbidity between these pain disorders is commonly seen in the clinic. Stress directly and indirectly affects the pathophysiological mechanisms related to migraine and plays an important role in the co\u2010occurrence and development of migraine, FMS, TMD, and IBS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We systematically searched PubMed and Web of Science databases, using combined keywords: stress, migraine, comorbidity, fibromyalgia syndrome, temporomandibular disorders, irritable bowel syndrome, pathological mechanisms, animal models, and treatment strategies, while emphasizing high impact studies. Literature was screened based on relevance, scientific rigor, and evidence level, prioritizing studies on stress\u2010related comorbidity mechanisms, models, or treatments. Exclusion criteria included single case reports, non\u2010full\u2010text conference abstracts, non\u2010English articles, low\u2010relevance studies, low\u2010quality methodologies, and general opinions (except authoritative consensus\/guidelines).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Clinical and preclinical studies support that potential stress\u2010related mechanisms underlie these comorbidities, including dysfunction of hypothalamic\u2013pituitary\u2013adrenal axis, dysregulation of autonomic nervous system, and central sensitization. We highlight the development and application of preclinical stress\u2010induced comorbid models as crucial tools for investigating these shared mechanisms. Stress targeted interventions have potential in managing these conditions, but mechanisms and efficacy stability remain to be clarified.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Stress may be a key driver of migraine and CPP comorbidities. Stress induced preclinical models support mechanism exploration, and stress\u2010targeted therapies hold promise for improving patient prognosis. Future research should deepen mechanistic studies and optimize models\/therapies to enhance clinical care.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.70004","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T05:34:12Z","timestamp":1764221652000},"page":"531-545","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The role of stress in the comorbidity of migraine and other chronic primary pain"],"prefix":"10.1111","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2457-4908","authenticated-orcid":false,"given":"Shi\u2010Jie","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Neurology The Second School of Clinical Medicine, Shaanxi University of Chinese Medicine  Xianyang China"},{"name":"Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research Xi'an Jiaotong University College of Stomatology  Xi'an 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