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1000亿美元的医疗成本和生产力损失(NIH，2006)。此外，据报道，与男性相比，女性在一些慢性疼痛方面的比例过高(例如，颞下颌关节紊乱症、关节炎、纤维肌痛)。然而，导致这些性别差异的机制尚未完全确定，因此，拟议的研究的总体目标是检查男性和女性在选定的内源性痛觉调制机制上是否存在差异。内源性疼痛调制的一种形式是运动诱导镇痛(EIA)。大量研究表明，运动后的疼痛可以减轻，而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，人们对男性和女性这种形式的内源性疼痛调制知之甚少。目前，EIA的机制尚不清楚，但动物研究结果表明，存在多种镇痛系统，而且在镇痛的神经化学中介方面存在性别差异。这项拟议研究的主要目的是检查男性和女性EIA的阿片类药物和内源性大麻类药物的机制。在拟议的研究中，将采用采用阿片类药物阻断方法的双盲安慰剂对照交叉设计。共有60名年龄在18-40岁之间的男女将被招募参加一次熟悉课程和两次随机分配的实验课程。参与者在双盲服用阿片类拮抗剂和安慰剂后，将在运动前和运动后接受疼痛测试(即有害的温度和压力刺激)。在运动前后抽血以检查运动对内源性大麻素的反应。了解为什么男性和女性对疼痛的敏感性不同，这对我们进一步了解疼痛的病因、机制和治疗具有重要意义 与公共健康相关：对疼痛的感知受到多种内源性止痛系统的调节，有证据表明，这些系统在男性和女性中的运作方式不同。鉴于许多临床疼痛状况在女性中的患病率大大高于男性，因此有必要更好地了解内源性疼痛抑制机制中的性别差异，这最终将允许定制更好的治疗方法，以增强男性和女性的疼痛控制。

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.