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: 7930147
• 负责人: Judith Tsui
• 金额: $ 15.03万
• 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/7930147
• 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; Etiology; Exhibits; Funding; Future; Goals; HIV; Hand; 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; 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; 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）：本申请是为波士顿大学医学院普通内科助理教授Judith Tsui博士申请的以患者为导向的研究职业发展奖（K23），她正在成为丙型肝炎病毒（HCV）相关结果的研究者。该研究计划既扩展了她以前在HCV方面的工作，又使她能够作为一名专注于物质使用者的疼痛研究人员朝着一个新的方向发展。该奖项将为Tsui博士提供必要的支持，以实现以下目标：1）发展慢性病毒感染（如HCV和HIV）的物质使用者慢性疼痛病因学的专业知识; 2）发表将导致改善物质使用者疼痛治疗的研究; 3）通过获得R 01过渡到独立资助的研究人员。全面的培训计划包括正式的课程，以及疼痛测量和实验疼痛模型的“动手”培训。崔博士的主要导师将是杰弗里·萨米特博士，他是物质使用和慢性病毒感染领域的知名研究者。她将接受来自领先的翻译疼痛研究员毛建仁博士和资深初级研究员兼临床心理学家罗伯特·爱德华兹博士的额外指导。疼痛是物质使用者的主要问题，需要更好地了解其病因以改善临床护理。有有限的研究来确定病毒感染，如HCV和HIV如何影响慢性疼痛和疼痛状况的风险。徐博士将探讨新的假设，即HCV与：1）在实验条件下对疼痛的超敏反应和2）临床疼痛。为了探索这些假设，Tsui博士将对HCV单感染者、HIV/HCV共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。她将收集一组120名阿片类药物依赖患者的丁丙诺啡或美沙酮：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; 3）重复针刺，以评估时间总和。该研究还将使用经验证的量表（如“简明疼痛量表”）收集疼痛和疼痛相关变量的数据，以及从外周血样本中测量促炎和抗炎细胞因子（TNF-1、IL-2、IL-6、IL-2、IL-10和IL-4）。她将进行适当的统计检验，以评估HCV感染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）以及自我报告的慢性疼痛的更高患病率，并探索炎症细胞因子是否介导HCV和疼痛之间的关联。这项研究将有助于我们了解物质使用者疼痛的原因，并将塑造未来的研究，以测试新的方法（可能包括抗HCV治疗），以预防和治疗这一脆弱患者群体的疼痛。 疼痛是目前和以前的药物使用者中的一个常见问题，其中许多人感染了HIV和HCV。为了有效地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的（但相对未探索的）问题：慢性病毒感染如何导致患者对疼痛的脆弱性？此外，它开始探索潜在的机制，疼痛超敏反应的HCV设置通过调查的作用，炎症细胞因子在塑造疼痛反应。这项研究的结果可能直接受益于有物质使用和疼痛史的患者，1）为他们的疼痛提供解释，2）导致改善疼痛治疗，包括抗HCV治疗或抗细胞因子药物（如pentoxyphylline）。此外，它将告知临床医生和政策制定者，他们在权衡治疗和干预措施的成本/效益以防止传播时必须考虑HCV感染的长期后果。