Attenuation of Pain in Men and Women: Mechanisms of Exercise-Induced Analgesia

描述（由申请人提供）：疼痛被认为是一个严重的国家健康问题，每年给这个国家造成超过1000亿美元的医疗费用和生产力损失（美国国立卫生研究院，2006年）。此外，据报道，与男性相比，女性在许多慢性疼痛状况（例如，颞下颌紊乱、关节炎、纤维肌痛）中的比例过高。然而，造成这些性别差异的机制尚未完全确定，因此，拟议研究的总体目标是检查男性和女性在内源性疼痛调节的选择机制上是否存在差异。内源性疼痛调节的一种形式是运动诱导镇痛（EIA）。许多研究表明，运动后疼痛的衰减，治疗性运动计划是治疗许多慢性疼痛综合征的重要因素。因此，令人惊讶的是，人们对这种形式的内源性疼痛调节在男性和女性中所知甚少。目前，我们对环境影响评估的机制知之甚少，但动物实验结果表明，存在多种镇痛系统，并且在镇痛的潜在神经化学介导方面存在性别差异。该研究的主要目的是研究阿片类药物和内源性大麻素在男性和女性中的EIA机制。采用阿片类药物阻断方法学的双盲安慰剂对照交叉设计将用于拟议的研究。总共将招募60名年龄在18-40岁之间的男性和女性参加一个熟悉阶段和两个随机分配的实验阶段。参与者在运动前后分别接受阿片类拮抗剂和安慰剂的双盲治疗，并接受疼痛测试（即有害的热和压力刺激）。在运动前后抽血检查内源性大麻素对运动的反应。了解为什么男性和女性在疼痛敏感性方面存在差异，对于进一步了解疼痛的病因、机制和治疗具有重要意义

DESCRIPTION (provided by applicant): Pain is considered to be a critical national health problem that costs this country over $100 billion each year in health costs and lost productivity (NIH, 2006). In addition, it has been reported that women are over-represented for a number of chronic pain conditions (e.g., temporomandibular disorders, arthritis, fibromyalgia) compared to men. The mechanisms responsible for these sex differences, however, have yet to be fully determined, thus, the overall objective of the proposed research is to examine whether men and women differ in selected mechanisms of endogenous pain modulation. One form of endogenous pain modulation is exercise-induced analgesia (EIA). Numerous studies have indicated an attenuation of pain following exercise, and therapeutic exercise programs are an important element in the treatment of many chronic pain syndromes. Thus, it is surprising how little is known regarding this form of endogenous pain modulation in men and women. Currently, the mechanisms responsible for EIA are poorly understood but results from the animal research indicate that multiple analgesic systems exist, and there are sex differences in the underlying neurochemical mediation of analgesia. The primary purpose of the proposed research is to examine opioid and endocannabinoid mechanisms of EIA in men and women. A double-blind placebo- controlled crossover design employing an opioid blockade methodology will be utilized in the proposed research. A total of 60 men and women between the ages of 18-40 yrs will be recruited to participate in a familiarization session and two randomly assigned experimental sessions. Participants will undergo pain testing (i.e., noxious thermal and pressure stimuli) before and after exercise following double-blind administration of an opioid antagonist and a placebo. Blood will be drawn before and following exercise to examine endocannabinoid responses to exercise. Understanding why men and women differ in pain sensitivity has important implications for furthering our knowledge of the etiology, mechanisms and treatment of pain PUBLIC HEALTH RELEVANCE: The perception of pain is modulated by multiple endogenous analgesic systems, and there is evidence that these systems operate differently in men and women. Given the substantially greater prevalence of many clinical pain conditions in women vs men, it is essential to gain a better understanding of sex differences in endogenous pain inhibitory mechanisms which will ultimately permit the tailoring of better treatments to enhance pain control in both men and women.