Female-selective mechanisms promoting migraine

Abstract

Sexual dimorphism has been revealed for many neurological disorders including chronic pain. Prelicinal studies and post-mortem analyses from male and female human donors reveal sexual dimorphism of nociceptors at transcript, protein and functional levels suggesting different mechanisms that may promote pain in men and women. Migraine is a common female-prevalent neurological disorder that is characterized by painful and debilitating headache. Prolactin is a neurohormone that circulates at higher levels in females and that has been implicated clinically in migraine. Prolactin sensitizes sensory neurons from female mice, non-human primates and humans revealing a female-selective pain mechanism that is conserved evolutionarily and likely translationally relevant. Prolactin produces female-selective migraine-like pain behaviors in rodents and enhances the release of calcitonin gene-related peptide (CGRP), a neurotransmitter that is causal in promoting migraine in many patients. CGRP, like prolactin, produces female-selective migraine-like pain behaviors. Consistent with these observations, publicly available clinical data indicate that small molecule CGRP-receptor antagonists are preferentially effective in treatment of acute migraine therapy in women. Collectively, these observations support the conclusion of qualitative sex differences promoting migraine pain providing the opportunity to tailor therapies based on patient sex for improved outcomes. Additionally, patient sex should be considered in design of clinical trials for migraine as well as for pain and reassessment of past trials may be warranted.

Progress and recognition of idiopathic intracranial hypertension: A narrative review

“…Sex‐based differences in terms of neurovascular functions, pathological brain lipid metabolism, and response to disease‐modifying therapies have been identified in a range of nervous system diseases, including ischemic stroke, Alzheimer's disease, Parkinson's disease, and migraine. 182 , 183 , 184 , 185 Complex interactions between hereditary elements and sex hormones may account for the different susceptibility to diseases in men and women. There is a lack of research on the impact of sexual dimorphism on IIH; further in‐depth and systematic research is necessary to unravel the underlying pathological processes specific to gender and to more effectively pinpoint potential therapeutic interventions.…”