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中的性别差异：社会心理和遗传影响摘要：疼痛是最昂贵，最普遍的公共卫生问题之一，妇女和少数民族面临的疼痛不足和厌恶疼痛的风险增加。与男性相比，女性报告的疼痛更加频繁，疼痛，并增加了多种疾病的疼痛患病率。妇女还代表了每年进行的4000万门门诊和门诊手术中的大多数。急性手术后疼痛和疼痛治疗不足是有据可查的，可长期康复，并有可能导致慢性长期疼痛状况的发展。尽管对镇痛功效的性别差异的发现不一致，但一致的报告表明，与男性相比，女性的不良药物反应（ADR）的经历在30％-75％之间。 ADR可以导致威胁生命的并发症，止痛治疗的停用，康复时间长时间和不合规。最近的药物基因组学研究表明，基因型可能导致药代动力学（PK）和药效学（PD）对某些药物的性别差异。在疼痛研究领域，对阿片类镇痛，相关副作用和治疗结果的性别差异，相关副作用和治疗结果对性别差异的遗传和非遗传贡献受到了有限的关注。这项研究将使用常见的急性临床疼痛模型来识别和表征会导致疼痛感知，镇痛和副作用性别差异的社会心理，生理和遗传因素。 AIM 1将确定对急性后术后疼痛的感知和生理反应的性别差异，并将检查这些性别与遗传，术前心理物理和心理社会因素有关的性别差异。 AIM 2将确定阿片类镇痛和副作用的性别差异，并将检查遗传，PK，PD和社会心理因素，这些因素解释了镇痛反应中群体差异。本研究将包括140名男性和女性患者（年龄范围16-45岁）。术前，我们将评估实验性疼痛反应和社会心理措施。我们将监测术后疼痛水平以及对阿片类药物芬太尼的PK/PD反应。我们将立即检查术后疼痛，镇痛反应和副作用的性别差异，并在手术后几个小时以及后期3天。该研究旨在为R01赠款提案建立基础，该建议支持临床上与临床相关的实验性疼痛研究的独立线。该项目将增强对疼痛转化研究以及疼痛及其治疗中健康差异的生物心理社会因素的理解，尤其是对妇女的治疗。此外，这项研究将洞悉与手术后疼痛和镇痛反应有关的复杂遗传，PK/PD过程，并将阐明对疼痛和副作用性别差异的生物心理社会贡献。最终目标是开发翻译研究，通过制定旨在提高女性生活质量的量身定制干预措施，减轻女性临床疼痛的负担，这与NIH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，妇女的疼痛治疗风险增加了。这项研究将使用常见的急性临床疼痛模型来识别和表征会导致疼痛感知，镇痛和副作用性别差异的社会心理，生理和遗传因素。最终目标是开发翻译研究，通过制定旨在提高女性生活质量的量身定制干预措施，减轻女性临床疼痛的负担，这与NIH女性健康研究办公室的优先事项一致。