Sex Differences in Acute Pain and Analgesic Responses: Psychosocial and Genetic I

描述(由申请人提供)：急性疼痛和止痛反应的性别差异：心理社会和遗传影响摘要：疼痛是最昂贵和最普遍的公共卫生问题之一，妇女和少数族裔面临着治疗不足和管理不善的风险增加。与男性相比，女性报告的疼痛更频繁、更剧烈，并且在多种情况下都增加了衰弱疼痛的患病率。在每年进行的4000万次门诊和门诊手术中，妇女也占大多数。术后急性疼痛和疼痛治疗不足是有充分记录的，会导致长期的恢复，并有可能发展为慢性长期疼痛状况。尽管在止痛效果方面性别差异的研究结果不一致，但一致的报告显示，女性比男性多经历30%-75%的不良药物反应(ADR)。不良反应可能导致危及生命的并发症、停止疼痛治疗、延长康复时间和不遵守规定。最近的药物基因组学研究表明，对某些药物的药代动力学(PK)和药效学(PD)反应的性别差异可能与基因有关。在疼痛研究领域，遗传和非遗传因素对阿片类药物镇痛、相关副作用和治疗结果的性别差异的影响有限。这项研究将使用一个常见的急性临床疼痛模型来识别和表征导致疼痛知觉、止痛和副作用的性别差异的心理、生理和遗传因素。目的1将确定术后急性疼痛的知觉和生理反应的性别差异，并研究这些反应与遗传、术前心理物理和心理社会因素的关系。目的2将确定阿片类药物止痛和副作用的性别差异，并将检查遗传、PK、PD和心理社会因素，以解释组内止痛反应的差异。140名男性和女性患者(年龄范围16-45岁)接受第三磨牙拔除手术。术前，我们将评估实验性疼痛反应和心理社会措施。我们将监测术后疼痛程度以及对阿片类芬太尼的PK/PD反应。我们将在术后即刻、术后数小时和术后3天检测术后疼痛、止痛反应和副作用方面的性别差异。这项研究旨在为R01拨款提案奠定基础，该提案支持一系列独立的与临床相关的实验性疼痛研究。该项目将加强对疼痛以及生物、心理和社会因素的翻译研究的了解，这些因素有助于疼痛及其治疗方面的健康差异，特别是对妇女而言。此外，这项研究将深入了解复杂的遗传，PK/PD过程涉及术后疼痛和止痛反应，并将阐明性别差异在疼痛和副作用中的生物心理社会贡献。最终目标是开发转化性研究，通过开发量身定制的干预措施来降低妇女日益增加的临床疼痛负担，以提高妇女的生活质量，与NIH妇女健康研究办公室的优先事项保持一致。与公共卫生相关：疼痛是美国最昂贵和最普遍的公共卫生问题之一，女性对疼痛治疗不足的风险增加。这项研究将使用一个常见的急性临床疼痛模型来识别和表征导致疼痛知觉、止痛和副作用的性别差异的心理、生理和遗传因素。最终目标是开发转化性研究，通过开发量身定制的干预措施来降低妇女日益增加的临床疼痛负担，以提高妇女的生活质量，与NIH妇女健康研究办公室的优先事项保持一致。

DESCRIPTION (provided by applicant): Sex Differences in Acute Pain and Analgesic Responses: Psychosocial and Genetic Influences ABSTRACT: Pain is one of the most costly and pervasive public health problems, with women and minorities facing increased risk for under-treated and mismanaged pain. Women, compared to men, report more frequent and intense pain and have increased prevalence of debilitating pain across a multitude of conditions. Women also represent the majority of the 40 million outpatient and ambulatory surgeries conducted each year. Acute post- operative pain and under-treatment of pain are well-documented and lead to prolonged recovery and potentially to development of chronic long-term pain conditions. Despite incongruent findings of sex differences in analgesic efficacy, consistent reports show that women experience between 30%-75% more adverse drug reactions (ADRs) compared to men. ADRs can lead to life-threatening complications, discontinuation of pain treatment, prolonged recovery and non-compliance. Recent pharmacogenomic studies have demonstrated that genotype may contribute to sex differences in pharmacokinetic (PK) and pharmacodynamic (PD) responses to certain drugs. Genetic and nongenetic contributions to sex differences in opioid analgesia, related side effects and treatment outcome have received limited attention in the field of pain research. This study will use a common acute clinical pain model to identify and characterize psychosocial, physiological and genetic factors that contribute to sex differences in pain perception, analgesia and side effects. Aim 1 will determine sex differences in perceptual and physiological responses to acute post-operative pain and will examine how those are related to genetic, pre-operative psychophysical and psychosocial factors. Aim 2 will determine sex differences in opioid analgesia and side effects and will examine genetic, PK, PD, and psychosocial factors that explain group differences in analgesic responses. 140 male and female patients (age range 16-45) who undergo third molar extraction will be included in this study. Preoperatively, we will assess experimental pain responses and psychosocial measures. We will monitor post-operative pain levels along with PK/PD responses to the opioid fentanyl. We will examine sex differences in post-operative pain, analgesic responses and side effects immediately and for several hours post-surgery and for 3 days post-procedure. The study is designed to build a foundation for a R01 grant proposal supporting an independent line of clinically-relevant experimental pain research. This project will enhance understanding of translational research in pain as well as biopsychosocial factors that contribute to health disparities in pain and its treatment, particularly for women. Additionally, this study will provide insight into the complex genetic, PK/PD processes involved in post- operative pain and analgesic responses and will elucidate biopsychosocial contributions to sex differences in pain and side effects. The ultimate goal is to develop translational research that will reduce the increased burden of clinical pain in women through the development of tailored interventions designed to enhance the quality of life for women, consistent with priorities of the NIH Office of Research on Women's Health. PUBLIC HEALTH RELEVANCE: Pain is one of the most costly and pervasive public health problems in the United States, and women are at increased risk for under-treatment of pain. This study will use a common acute clinical pain model to identify and characterize psychosocial, physiological and genetic factors that contribute to sex differences in pain perception, analgesia and side effects. The ultimate goal is to develop translational research that will reduce the increased burden of clinical pain in women through the development of tailored interventions designed to enhance the quality of life for women, consistent with priorities of the NIH Office of Research on Women's Health.