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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23DA027367-04
Application #
8471080
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Khalsa, Jagjitsingh H
Project Start
2010-06-01
Project End
2014-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
4
Fiscal Year
2013
Total Cost
$161,973
Indirect Cost
$11,998
Name
Boston Medical Center
Department
Type
DUNS #
005492160
City
Boston
State
MA
Country
United States
Zip Code
02118
Tsui, Judith I; Anderson, Bradley J; Strong, David R et al. (2014) Craving predicts opioid use in opioid-dependent patients initiating buprenorphine treatment: a longitudinal study. Am J Drug Alcohol Abuse 40:163-9
Tsui, Judith I; Cheng, Debbie M; Coleman, Sharon M et al. (2014) Pain is associated with risky drinking over time among HIV-infected persons in St. Petersburg, Russia. Drug Alcohol Depend 144:87-92
Tsui, Judith I; Cheng, Debbie M; Coleman, Sharon M et al. (2013) Pain is associated with heroin use over time in HIV-infected Russian drinkers. Addiction 108:1779-87
Tsui, Judith I; Cheng, Debbie M; Libman, Howard et al. (2013) Risky alcohol use and serum aminotransferase levels in HIV-infected adults with and without hepatitis C. J Stud Alcohol Drugs 74:266-70
Tsui, Judith I; Cheng, Debbie M; Libman, Howard et al. (2012) Hepatitis C virus infection is associated with painful symptoms in HIV-infected adults. AIDS Care 24:820-7
Evans, Jennifer L; Tsui, Judith I; Hahn, Judith A et al. (2012) Mortality among young injection drug users in San Francisco: a 10-year follow-up of the UFO study. Am J Epidemiol 175:302-8
Tsui, Judith I; Herman, Debra S; Kettavong, Malyna et al. (2011) Chronic pain and hepatitis C virus infection in opioid dependent injection drug users. J Addict Dis 30:91-7
Tsui, Judith I; Herman, Debra S; Kettavong, Malyna et al. (2011) Escitalopram is associated with reductions in pain severity and pain interference in opioid dependent patients with depressive symptoms. Pain 152:2640-4