Neuroimmunological mechanisms linking primary dysmenorrhea and migraine: a systematic review of the literature
Abstract
Introduction and Purpose: Primary dysmenorrhea and migraine are among the most prevalent pain disorders in women of reproductive age, often coexisting and exhibiting overlapping pathophysiological mechanisms. This systematic review aims to identify and summarize the shared neuroimmunological pathways that may underlie both conditions, with particular emphasis on inflammatory mediators, neuropeptides, hormonal modulation, and glial activation.
Results: The analysis of studies published between 2000 and 2025 reveals consistent evidence of increased levels of proinflammatory cytokines (IL-1β, IL-6, TNF-α) and prostaglandins (especially PGE₂) in both disorders. These mediators contribute to peripheral and central sensitization, amplifying nociceptive signaling. Pain-related neuropeptides such as calcitonin gene-related peptide (CGRP) and substance P are involved in neurogenic inflammation, vascular dysregulation, and microglial activation within central pain pathways. Moreover, estrogen fluctuations appear to modulate both immune and neuronal responses, influencing microglial phenotype and cytokine release, thereby explaining the cyclic nature and female predominance of these conditions.
Conclusion: Dysmenorrhea and migraine share a common neuroimmune-endocrine framework, in which inflammatory mediators, neuropeptides, and hormonal fluctuations interact to enhance pain sensitivity. Recognition of these shared mechanisms provides a foundation for developing integrated therapeutic…
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Evidence Hub reads this as a systematic review. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid.
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