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）：此申请是为波士顿大学医学院普通内科医学助理教授朱迪思·托伊（Judith Tsui）博士颁发的，该申请为乙型肝炎病毒（HCV）的研究人员确立了自己的研究人员。该研究计划都扩展了她在HCV中的先前工作，并且使她能够朝着新的方向发展，因为疼痛研究人员专注于药物使用者。该奖项将为TSUI博士提供实现以下目标所需的支持：1）在患有HCV和HIV等慢性病毒感染的药物使用者的慢性疼痛病因方面发展专业知识； 2）发表研究，这将导致药物使用者疼痛的治疗方法改善； 3）通过获得R01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性疼痛模型的“动手”培训。 TSUI博士的主要导师将是杰弗里·萨梅特（Jeffrey Samet）博士，他是药物使用和慢性病毒感染领域的既定研究者。她将获得转化疼痛研究员Jianren Mao博士的额外指导，以及成熟的初级研究员和临床心理学家Robert Edwards博士。疼痛是药物使用者的主要问题，需要更好地了解其病因来改善临床护理。有限的研究来确定HCV和HIV等病毒感染如何影响慢性疼痛和疼痛状况的风险。 TSUI博士将探讨HCV与：1）在实验条件下对疼痛的过敏性和2）临床疼痛相关的新型假设。为了探讨这些假设，TSUI博士将对HCV单感染，HIV/HCV共感染和未感染的阿片类药物成瘾者进行实验性的横断面研究，以比较实验性疼痛反应和自我报告的临床疼痛。她将在丁丙诺啡或美沙酮上组成120例阿片类药物依赖性患者的队列：40 HCV+/HIV-，40 HCV+/HIV+和40 HCV-/HIV控制。参与者将经过以下实验测试：1）评估冷疼痛耐受性的冷压测试2）机械刺激以测试机械疼痛阈值，而3）重复的针刺以评估时间求和。该研究还将使用经过验证的量表（例如“短暂疼痛清单”）以及对促炎和抗炎细胞因子的测量（TNF-1，IL-2，IL-6，IL-6，IL-2，IL-10和IL-4），从外围血样品中收集有关疼痛和疼痛相关变量的数据。她将进行适当的统计测试，以评估受HCV感染的阿片类药物成瘾者（单独使用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/阈值和更多的时间刺激）以及更高的自我报道性慢性疼痛的普遍性，并且可以探索炎症性cytokines seartokines erisation Seartive sissiation sissiation sissiation sepediation sissiation sissiation sissiation seped sissiation和HCV之间。这项研究将有助于我们理解药物使用者疼痛的原因，并将塑造未来的研究以测试新方法（可能包括抗HCV治疗），以预防和治疗这一脆弱的患者人群的疼痛。 公共卫生相关性：疼痛是当前和以前的药物使用者的常见问题，其中许多人感染了艾滋病毒和HCV。需要更好地了解疼痛病因，以便在患有药物使用问题的患者中有效预防和治疗慢性疼痛。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疼痛的脆弱性？此外，它通过研究炎症细胞因子在塑造疼痛反应中的作用，开始探索HCV疼痛超敏反应的潜在机制。这项研究的结果可能会直接使患有药物使用史和疼痛病史的患者受益1）提供疼痛的解释，2）改善疼痛的治疗方法，包括抗HCV疗法或抗促性因子药物（例如五氧肾上腺素）。此外，它将告知临床医生和政策制定者，他们在权衡治疗成本/治疗成本和防止传播的干预措施时必须考虑HCV感染的长期后果。