HCV and Pain in Substance Users With and Without HIV

丙型肝炎病毒（HCV）与吸毒者和未感染艾滋病毒的人的疼痛

• 批准号: 8259449
• 负责人: Judith Tsui
• 金额: $ 16.72万
• 依托单位: BOSTON MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8259449
• 关键词: Address; Alcohol or Other Drugs use; Anti-Inflammatory Agents; Anti-inflammatory; Award; Blood specimen; Boston; Brief Pain Inventory; Buprenorphine; Chronic; Clinical; Clinical Investigator; Costs and Benefits; Cross-Sectional Studies; Data; Development; Environmental Wind; Etiology; Exhibits; Funding; Future; Goals; HIV; Health; Hepatitis C; Hepatitis C virus; High Prevalence; Hypersensitivity; Immune; Infection; Inflammatory; Interleukin-10; Interleukin-2; Interleukin-4; Interleukin-6; Internal Medicine; Intervention; Intervention Studies; K-Series Research Career Programs; Lead; Learning; Measurement; Measures; Mechanics; Mediating; Mentors; Methadone; Modeling; Mono-S; Neuroimmunomodulation; Neuropathy; Opioid; Outcome; Pain; Pain Measurement; Pain Threshold; Participant; Pathologic; Patient Self-Report; Patients; Pharmaceutical Preparations; Play; Policy Maker; Process; Prospective Studies; Psychologist; Publishing; Recording of previous events; Recruitment Activity; Research; Research Design; Research Personnel; Risk; Role; Shapes; Stimulus; TNF gene; Testing; Training; Tumor Necrosis Factor-alpha; Universities; Viral; Virus Diseases; Vulnerable Populations; Work; anti-hepatitis C; chronic pain; clinical care; cohort; cytokine; experience; human TNF protein; human subject; improved; medical schools; multi-component intervention; novel; novel strategies; patient oriented research; patient population; peripheral blood; prevent; professor; public health relevance; research study; response; skills; transmission process

DESCRIPTION (provided by applicant): This application is for a Patient-Oriented Research Career Development Award (K23) for Dr. Judith Tsui, an Assistant Professor in General Internal Medicine at Boston University School of Medicine, who is establishing herself as an investigator in hepatitis C virus (HCV) related outcomes. The research plan both extends her prior work in HCV, and allows her to grow in a new direction as a pain researcher focusing on substance users. The award will provide Dr. Tsui with the support necessary to accomplish the following goals: 1) develop expertise in the etiology of chronic pain in substance users with chronic viral infections like HCV and HIV; 2) publish research that will lead to improved treatments for pain among substance users; and 3) transition into an independently funded researcher by obtaining an R01. The comprehensive training plan includes formal coursework, as well as "hands-on" training in pain measurement and experimental pain models. Dr. Tsui's primary mentor will be Dr. Jeffrey Samet, an established investigator in the fields of substance use and chronic viral infections. She will receive additional mentoring from Dr. Jianren Mao, a leading translational pain researcher, and Dr. Robert Edwards, an accomplished junior investigator and clinical psychologist. Pain is a major problem among substance users, and a better understanding of its etiology is needed to improve clinical care. There is limited research to determine how viral infections such as HCV and HIV impact risk for developing chronic pain and painful conditions. Dr. Tsui will explore the novel hypotheses that HCV is associated with: 1) hypersensitivity to pain under experimental conditions and 2) clinical pain. To explore these hypotheses, Dr. Tsui will conduct an experimental, cross-sectional study of HCV mono- infected, HIV/HCV co-infected, and uninfected opioid addicts that compares experimental pain responses and self-reported clinical pain. She will assemble a cohort of 120 opioid dependent patients on buprenorphine or methadone: 40 HCV+/HIV-, 40 HCV+/HIV+ and 40 HCV-/HIV-controls. Participants will undergo the following experimental testing: 1) the cold-pressor test to assess cold pain tolerance 2) mechanical stimulus to test mechanical pain thresholds and 3) repetitive pinprick to assess for temporal summation. The study will also collect data on pain and pain-related variables using validated scales such as the "Brief Pain Inventory", as well as measurements of pro- and anti-inflammatory cytokines (TNF-1, IL-2, IL-6, IL-2, IL-10 and IL-4) from peripheral blood samples. She will perform appropriate statistical testing to assess whether opioid addicts who are HCV infected (HCV+ alone or HCV+/HIV+) have different experimental pain responses (lower pain tolerance/thresholds and more temporal summation) and a higher prevalence of self-reported chronic pain, and to explore whether inflammatory cytokines mediate found associations between HCV and pain. This research will contribute to our understanding of the causes of pain among substance users, and will shape future studies to test new approaches (possibly including anti-HCV treatment) to prevent and treat pain in this vulnerable patient population. PUBLIC HEALTH RELEVANCE: Pain is a common problem among current and former substance users, many of whom are infected with HIV and HCV. A better understanding of pain etiology is needed in order to effectively prevent and treat chronic pain among patients with substance use problems. This research addresses the simple (yet relatively unexplored) question: how do chronic viral infections contribute to patients' vulnerability to pain? In addition, it begins to explore potential mechanisms for pain hypersensitivity in the setting of HCV by investigating the role of inflammatory cytokines in shaping pain responses. The results of this research may directly benefit patients with a history of substance use and pain by 1) providing an explanation for their pain and 2) leading to improved treatments for pain, including anti-HCV therapy or anti-cytokine medications (such as pentoxyphylline). In addition, it will inform clinicians and policy makers who must consider the long-term consequences of HCV infection when weighing costs/benefits of treatment and interventions to prevent transmission.

描述（由申请人提供）：本申请旨在为波士顿大学医学院普通内科助理教授 Judith Tsui 博士申请以患者为导向的研究职业发展奖 (K23)，她正在将自己定位为一名研究人员丙型肝炎病毒（HCV）相关结果。该研究计划既扩展了她之前在丙型肝炎方面的工作，又让她能够在新的方向上成长，成为一名专注于物质使用者的疼痛研究员。该奖项将为徐博士提供实现以下目标所需的支持：1）发展患有慢性病毒感染（如 HCV 和 HIV）的物质使用者的慢性疼痛病因学方面的专业知识； 2) 发表研究成果，改善药物滥用者的疼痛治疗方法； 3) 通过获得 R01 转变为独立资助的研究人员。全面的培训计划包括正式课程以及疼痛测量和实验疼痛模型的“实践”培训。 Tsui 博士的主要导师是 Jeffrey Samet 博士，他是药物滥用和慢性病毒感染领域的资深研究员。她还将获得领先的转化疼痛研究员毛建仁博士和卓有成就的初级研究员和临床心理学家罗伯特·爱德华兹博士的额外指导。疼痛是药物使用者的一个主要问题，需要更好地了解其病因以改善临床护理。目前尚无研究确定 HCV 和 HIV 等病毒感染如何影响慢性疼痛和痛苦状况的风险。 Tsui 博士将探讨 HCV 与以下因素相关的新假设：1) 实验条件下对疼痛过敏；2) 临床疼痛。为了探索这些假设，Tsui 博士将对 HCV 单一感染者、HIV/HCV 共同感染者和未感染的阿片类药物成瘾者进行一项实验性横断面研究，比较实验性疼痛反应和自我报告的临床疼痛。她将组建一个由 120 名服用丁丙诺啡或美沙酮的阿片类药物依赖患者组成的队列：40 名 HCV+/HIV-、40 名 HCV+/HIV+ 和 40 名 HCV-/HIV-对照。参与者将接受以下实验测试：1）冷加压测试以评估冷痛耐受性2）机械刺激以测试机械疼痛阈值和3）重复针刺以评估时间总和。该研究还将使用经过验证的量表（例如“简要疼痛量表”）收集有关疼痛和疼痛相关变量的数据，以及促炎和抗炎细胞因子（TNF-1、IL-2、IL-6、来自外周血样本的 IL-2、IL-10 和 IL-4）。她将进行适当的统计测试，以评估感染 HCV 的阿片类药物成瘾者（单独 HCV+ 或 HCV+/HIV+）是否具有不同的实验性疼痛反应（较低的疼痛耐受性/阈值和更多的时间总和）以及较高的自我报告慢性疼痛患病率，并探讨炎症细胞因子是否介导 HCV 与疼痛之间的关联。这项研究将有助于我们了解药物滥用者疼痛的原因，并将影响未来的研究，以测试新方法（可能包括抗丙肝病毒治疗），以预防和治疗这一弱势患者群体的疼痛。 公共卫生相关性：疼痛是当前和以前的药物使用者的一个常见问题，其中许多人感染了艾滋病毒和丙型肝炎病毒。为了有效预防和治疗有物质使用问题的患者的慢性疼痛，需要更好地了解疼痛病因。这项研究解决了一个简单（但相对尚未探索）的问题：慢性病毒感染如何导致患者容易遭受疼痛？此外，它还开始通过研究炎症细胞因子在塑造疼痛反应中的作用来探索 HCV 环境下疼痛超敏反应的潜在机制。这项研究的结果可能会直接使有物质使用史和疼痛史的患者受益，方法是：1) 为他们的疼痛提供解释，2) 改进疼痛治疗方法，包括抗 HCV 治疗或抗细胞因子药物（如己酮茶碱） ）。此外，它还将告知临床医生和政策制定者，他们在权衡预防传播的治疗和干预措施的成本/效益时必须考虑丙型肝炎病毒感染的长期后果。