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

急性疼痛和镇痛反应的性别差异：社会心理和遗传 I

• 批准号: 7740285
• 负责人: BARBARA A HASTIE
• 金额: $ 21.85万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-10 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7740285
• 关键词: Absence of pain sensation; Accounting; Acute; Acute Pain; Adverse effects; Adverse reactions; Affective; Age; Ambulatory Surgical Procedures; Analgesics; Anxiety; Applications Grants; Attention; CYP3A4 gene; Catechol O-Methyltransferase; Chronic; Clinical; Complex; Data; Development; Drug Kinetics; Female; Fentanyl; Foundations; Frequencies; Fright; Genetic; Genetic Markers; Genotype; Goals; Hour; Human; Laboratories; Lead; Life; Measures; Methyltransferase Gene; Minority; Modeling; Monitor; Operative Surgical Procedures; Opioid; Opioid Receptor; Outpatients; Pain; Pain Research; Patients; Perception; Pharmaceutical Preparations; Pharmacodynamics; Pharmacogenetics; Pharmacogenomics; Pharmacology; Physiological; Population; Postoperative Pain; Postoperative Period; Prevalence; Procedures; Process; Psychophysiology; Psychosocial Factor; Public Health; Quality of life; Reaction; Receptor Gene; Recovery; Reporting; Research; Risk; Sensory; Sex Characteristics; Side; Technology; Translational Research; Treatment outcome; United States; United States National Institutes of Health; Visual; Woman; Women' s Health; abstracting; analog; base; biopsychosocial; chronic pain; clinically relevant; design; experience; health disparity; insight; instrument; intense pain; male; men; non-compliance; non-genetic; pressure; psychologic; psychosocial; public health relevance; response; sex; therapy design; third molar extraction; young adult

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.

描述（由申请人提供）：急性疼痛和镇痛反应的性别差异：社会心理和遗传影响 摘要：疼痛是代价最高、最普遍的公共卫生问题之一，女性和少数族裔面临的疼痛治疗不足和处理不当的风险增加。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，衰弱性疼痛的发生率更高。每年进行的 4000 万例门诊和门诊手术中，女性也占大多数。术后急性疼痛和疼痛治疗不足已有充分记录，会导致恢复时间延长，并可能发展为慢性长期疼痛状况。尽管镇痛功效的性别差异的研究结果不一致，但一致的报告表明，与男性相比，女性经历的药物不良反应 (ADR) 多出 30%-75%。不良反应可能导致危及生命的并发症、停止疼痛治疗、延长恢复时间和不依从治疗。最近的药物基因组学研究表明，基因型可能导致对某些药物的药代动力学（PK）和药效（PD）反应的性别差异。遗传和非遗传对阿片类镇痛性别差异、相关副作用和治疗结果的影响在疼痛研究领域受到的关注有限。这项研究将使用常见的急性临床疼痛模型来识别和表征导致疼痛感知、镇痛和副作用方面性别差异的社会心理、生理和遗传因素。目标 1 将确定对术后急性疼痛的感知和生理反应的性别差异，并将研究这些差异与遗传、术前心理物理和心理社会因素的关系。目标 2 将确定阿片类镇痛和副作用的性别差异，并将检查解释镇痛反应群体差异的遗传、PK、PD 和心理社会因素。本研究将纳入 140 名接受第三磨牙拔除的男性和女性患者（年龄范围 16-45 岁）。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水平以及对阿片类芬太尼的 PK/PD 反应。我们将立即、术后数小时和术后 3 天检查术后疼痛、镇痛反应和副作用的性别差异。该研究旨在为 R01 拨款提案奠定基础，支持独立的临床相关实验疼痛研究。该项目将增进对疼痛转化研究以及导致疼痛及其治疗健康差异的生物心理社会因素的理解，特别是对女性而言。此外，这项研究将深入了解与术后疼痛和镇痛反应有关的复杂遗传、PK/PD 过程，并将阐明生物心理社会对疼痛和副作用性别差异的影响。最终目标是开展转化研究，通过制定旨在提高女性生活质量的定制干预措施，减轻女性日益增加的临床疼痛负担，这与美国国立卫生研究院女性健康研究办公室的优先事项一致。公共卫生相关性：疼痛是美国最昂贵、最普遍的公共卫生问题之一，女性遭受疼痛治疗不足的风险更大。这项研究将使用常见的急性临床疼痛模型来识别和表征导致疼痛感知、镇痛和副作用方面性别差异的社会心理、生理和遗传因素。最终目标是开展转化研究，通过制定旨在提高女性生活质量的定制干预措施，减轻女性日益增加的临床疼痛负担，这与美国国立卫生研究院女性健康研究办公室的优先事项一致。