Chronic Pain

Title: Stress and Opioid Misuse Risk: The Role of Endogenous Opioid and Endocannabinoid Mechanisms

Funded by the National Institute on Drug Abuse (R01DA050334), PI: Bruehl, Vanderbilt University Medical Center

Elevated stress is known to enhance risk for opioid use disorder (OUD), a significant problem given the frequent use of opioid analgesics in chronic pain management.  This project targeting patients with chronic low back pain will test an innovative model in which low endogenous opioid (EO) and endocannabinoid (EC) activity associated with elevated stress both contribute to increased OUD risk via their association with heightened reinforcing effects of opioids (e.g., drug liking).  Results will provide important new mechanistic understanding of how stress increases OUD risk, and may identify a novel and clinically-pragmatic marker of risk-enhancing differential opioid responding.


Title: Integrated Health Services to Reduce Opioid Use While Managing Chronic Pain

Funded by the Patient-Centered Outcomes Research Institute (PCORI), PI: McCormack, RTI International, Site PI: Archer, Vanderbilt University Medical Center

Recently declared a public health emergency, opioids have claimed the lives of over half a million people between 2000 to 2015. Every day an average of 91 Americans die from an opioid overdose. One of the driving forces of this epidemic has been the use of prescription opioids for chronic pain. However the effectiveness of opioid therapy is unclear and exposes patients to potential risks, including addiction. Safer treatment options for long term management of chronic pain are needed.

This pragmatic trial is a collaboration between RTI International, Vanderbilt University Medical Center, University of North Carolina, and Duke University. Dr. Archer is the site PI for the Vanderbilt site. This trial will help patients better understand the risks, benefits, and uncertainties associated with opioid use and will receive other treatment options for managing their pain. Patients on chronic opioid therapy seen in primary care or pain clinics will be randomized to guideline-concordant pharmacotherapy with shared decision making (Arm 1) or guideline-concordant pharmacotherapy with motivational interviewing (MI) and cognitive behavioral therapy (Arm 2). (…


Title: Evaluating Specific and Non-Specific Mechanisms in Two Distinct Complementary/ Integrative Interventions for Chronic Pain

Funded by the National Center for Complementary and Integrative Health (R01AT009680-04), PI: Bruehl, Vanderbilt University Medical Center; Burns, Rush University

Non-drug interventions for management of chronic back pain are being increasingly used by patients. While there is evidence that such interventions can help patients manage their pain more effectively, there is little evidence regarding how these interventions exert their beneficial effects. This project focuses on two common complimentary medicine interventions: mindfulness therapy and spinal manipulation therapy. Patients with chronic back pain will be randomized to receive one of these two interventions for 8 weeks, and will participate in laboratory assessment sessions to evaluate pain sensitivity and natural pain inhibition mechanisms before starting the intervention, after the 4th intervention session, and again after completion of the 8th intervention session. The aim of this study is to determine the extent to which beneficial effects of the two interventions are due to theory-specific mechanisms (mindfulness changes for mindfulness therapy, spinal flexibility for spinal manipulation therapy) versus non-specific mechanisms such as changes in the body's natural ability to inhibit pain or psychological changes. 


Title: Optimizing Psychosocial Treatment of Interstitial Cystitis/Bladder Pain Syndrome

Funded by the National Institute of Diabetes and Digestive and Kidney Disease (K23DK118118) PI: McKernan, Vanderbilt University Medical Center

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a severe pain condition affecting 3-8 million people in the United States lacking treatments that work. Emotional suffering is common in IC/BPS and known to make physical symptoms worse, and studies show patient sub-groups respond differently to treatment. By creating and testing a psychosocial intervention specific to IC/BPS, we will learn if this intervention improves patient wellness, who the intervention works best for, and how the body’s pain processing influences outcomes.  (


Title: Fibromyalgia TENS in Physical Therapy Study (TIPS): an embedded pragmatic clinical trial

Funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (UH3AR076387), PI: Crofford, Vanderbilt University Medical Center; Sluka, University of Iowa

Fibromyalgia is a chronic pain condition characterized by widespread musculoskeletal pain, tenderness, and stiffness associated with fatigue and sleep disturbance. TENS has been shown to be effective for this patient population; however, TENS is underused by physical therapists in clinical practice. This pragmatic trial is being conducted to compare effectiveness of physical therapy with or without the addition of TENS for patients with fibromyalgia.  (


Title: Psychosocial and Oxidative Stress Mechanisms of Post-surgical Chronic Pain

Funded by the National Institutes of Health (R01AG048915), PI: Bruehl, Vanderbilt University Medical Center

Total knee arthroplasty (TKA) is an increasingly common surgical procedure in older adults.  Although effective for many patients, 15% or more experience unsatisfactory pain outcomes.  While limited to post-surgical chronic pain in some patients, others also develop reginal allodynia and hyperalgesia, edema, and autonomic features indicating Complex Regional Pain Syndrome (CRPS), a particularly difficult to treat chronic pain condition.  The mechanisms of post-TKA chronic pain and CRPS are not well understood.  The most common TKA procedure involves application of a tourniquet to the operated limb for extended periods (up to ≈ 2 hours).  Animal models indicate that extended tourniquet application followed by reperfusion when the tourniquet is removed leads to ischemic reperfusion injury, which via increased oxidative stress can result in prolonged neuropathic pain and clinical features of CRPS.  One key objective of this project is to examine for the first time in humans the impact of baseline and perioperative oxidative stress, as indexed by F2 - isoprostanes, on long-term pain, CRPS, and functional outcomes following TKA.  One known predictor of post-TKA chronic pain is greater preoperative negative affect (specifically, depression and anxiety).  Emerging literature suggests that elevated depression and anxiety may be associated with elevated oxidative stress levels.