PDF(Pubmed)
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.
摘要：
性二态性已被揭示为许多神经系统疾病，包括慢性疼痛。男性和女性人类捐献者的前期研究和验尸分析揭示了转录本上伤害感受器的性二态性，蛋白质和功能水平表明可能促进男性和女性疼痛的不同机制。偏头痛是一种常见的女性普遍存在的神经系统疾病，其特征是疼痛和衰弱性头痛。催乳素是一种神经激素，在女性中以较高的水平循环，临床上与偏头痛有关。催乳素使雌性小鼠的感觉神经元敏感，非人类灵长类动物和人类揭示了一种女性选择性疼痛机制，这种机制在进化上是保守的，并且可能在翻译上是相关的。催乳素在啮齿动物中产生女性选择性偏头痛样疼痛行为，并增强降钙素基因相关肽（CGRP）的释放，一种神经递质，在许多患者中促进偏头痛。CGRP,像催乳素,产生女性选择性偏头痛样疼痛行为。与这些观察结果一致，公开的临床数据表明,小分子CGRP受体拮抗剂优先用于治疗女性急性偏头痛.总的来说，这些观察结果支持了导致偏头痛的定性性别差异的结论,这为根据患者性别定制治疗方法以改善结局提供了机会.此外,在设计偏头痛和疼痛的临床试验时,应考虑患者性别,并可能需要对过去的试验进行重新评估.
