– As part of the National Institutes of Health
(NIH) Helping to End Addiction Long-term, or the NIH HEAL Initiative, researchers from UPMC
and the University of Pittsburgh
have been awarded nine grants totaling more than $32 million to improve prevention and treatment strategies for opioid misuse and addiction and to enhance pain management.
The awards are part of 375 grant awards across 41 states made by the NIH in fiscal year 2019 to apply scientific solutions to reverse the national opioid crisis.
“It has become regrettably clear that we need a substantially larger basic and clinical research effort to develop new ways to prevent and treat opioid addiction, and change how we address chronic pain,” said Arthur S. Levine, M.D., senior vice chancellor for the Pitt Schools of the Health Sciences and John and Gertrude Petersen Dean of Medicine at the Pitt School of Medicine. “The scale of these NIH grants awarded to Pitt and UPMC is a testament to the outstanding research by our physicians and scientists at the frontlines of the fight against the opioid epidemic.”
“UPMC and Pitt have been deeply committed to caring for those affected by the opioid epidemic in our communities,” said Steven D. Shapiro, M.D., chief medical and scientific officer of UPMC. “These grants reflect our leadership in conducting evidence-based research into addiction and pain management and our ability to quickly implement them into clinical practice to ensure the well-being of our patients.”
The UPMC and Pitt projects supported by the NIH HEAL initiative are:
Low Back Pain: Biological, Biomechanical, Behavioral Phenotypes Mechanistic Research Center (LB3P MRC)
Primary investigators Gwendolyn Sowa, M.D., Ph.D., of Pitt’s Department of Physical Medicine and Rehabilitation and the UPMC Rehabilitation Institute, and Nam Vo, Ph.D., of the Department of Orthopaedic Surgery, were awarded $21.5 million to establish the LB3P MRC, a multidisciplinary research center dedicated to categorizing patients into chronic low back pain subgroups with the goal of targeting treatments specific to individual patients’ pain and reducing the use of opioids.
LB3P MRC’s unique approach of integrating the biological, biomechanical and behavioral contributors to chronic low back pain with novel mathematical modeling will ultimately provide predictive tools to help personalize treatments for this common and debilitating condition.
Proof of Concept Study to Treat Negative Affect in Chronic Low Back Pain
Principal investigator Ajay D. Wasan, M.D., M.Sc., of Pitt’s Department of Anesthesiology and Perioperative Medicine, received $3.4 million to address the need for better evidence-based pain treatment for patients with chronic low back pain who have co-occurring mental health disorders, such as major depression or anxiety.
An estimated 20% to 30% of the 50 million adults with chronic low back pain in this country also have a coexisting mood disorder and are prescribed opioids more frequently and misuse opioids at a greater rate than the general population. This project will examine if the combination of antidepressants and fear-avoidance physical therapy is a more effective treatment option to improve pain, depression, anxiety and function, and prevent opioid misuse.
University of Pittsburgh Hub and Spoke Pain Clinical Trial Network
Wasan and the Pitt Department of Anesthesiology and Perioperative Medicine also received over $1 million to conduct more rigorous multi-site pain clinical trials with an experienced multidisciplinary team of investigators. One of the key steps to establishing more effective non-opioid treatments for pain is infrastructure for the rapid design and performance of high-quality Phase 2 clinical trials to test promising novel therapeutics for pain.
The University of Pittsburgh Hub and Spoke Clinical Trials Network is poised to take on this role and a wide range of trials and duties, as well as be a mechanism to train younger pain clinical researchers in the conduct of rigorous, collaborative and multi-site studies.
Integrated Approach to Pain and Opioid Use in Hemodialysis Patients: The Hemodialysis Opioid Prescription Effort (HOPE) Consortium
Principal investigators Manisha Jhamb, M.D., M.P.H., of Pitt’s Department of Medicine, Jane Liebschutz, M.D., and Jonathan Yabes, Ph.D., of the Division of General Internal Medicine, and Jennifer Steel, Ph.D., of the Department of Surgery, received $2.8 million to improve pain management in patients with end-stage renal disease who report debilitating pain while on dialysis, which is oftentimes managed poorly and ineffectively with a high prevalence of opioid use.
As part of the HOPE consortium, they will join researchers across the country to compare different strategies to improve pain and ensure safe opioid use in patients on hemodialysis. These strategies will include medication-assisted pain treatment with a focus on opioid tapering; transitioning patients to buprenorphine when appropriate; collaborative care models; and behavioral pain management.
Sleep and Circadian-Dependent Mechanisms Contributing to Opiate Use Disorder and Response to Medication Assisted Treatment
Principal investigator Ryan W. Logan, Ph.D., of Pitt’s Department of Psychiatry received $1.6 million to address sleep and circadian disruptions among people with an opioid use disorder.
The most common complaints among patients with an opioid use disorder are sleep loss, poor sleep quality and altered sleep-wake cycles, which are speculated to foster opioid craving and relapse. This project will dissect the molecular and cellular mechanisms in the brain that underlie the associations between circadian rhythm disruptions and the vulnerability to opioid relapse, with the goal to drive the development of novel therapeutics for opioid use disorder.
Joint Pain on a Chip: Mechanistic Analysis, Therapeutic Targets, and an Empirical Strategy for Personalized Pain Management
Principal investigators Michael Gold, Ph.D., of Pitt’s Department of Neurobiology, and Hang Lin, Ph.D., of Pitt’s Department of Orthopaedic Surgery, received $1.2 million to study osteoarthritis using the microJoint, a three-dimensional tissue chip developed at Pitt that replicates a human joint on a small scale. The researchers will use the microJoint to study osteoarthritis pain and test drugs, and also assess the impact of opioids on the neural activity and tissue health in the knee joint.
Long-term Activation of Spinal Opioid Analgesia After Inflammation
Principal investigator Bradley Taylor, Ph.D., of Pitt’s Department of Anesthesiology and Perioperative Medicine, was awarded an additional $400,000 for the final year of a five-year, $3 million grant from the NIH that was originally awarded in 2015 to study natural biological mechanisms of pain relief.
The research project follows findings Taylor and his team announced in a 2013 Science article describing how injury and inflammation can increase the body’s natural ability to produce pain relief. In the NIH study, the researchers are investigating how this built-in pain relief mechanism works at the neurobiological, cellular and molecular levels in the brain and spinal cord in an effort to validate a new target for chronic pain therapy.
Prevention of Opioid Diversion by Young Adult Patients: Primary and Specialty Care Practices and Perspectives
Principal investigator Brooke S.G. Molina, Ph.D., of Pitt’s Department of Psychiatry, received more than $300,000 to continue research based in primary care that focuses on preventing the misuse and diversion of abusable prescription medications by young adults.
The project will characterize the physician and staff practices, experiences and perspectives that drive their ability to adopt recommended opioid prescribing practices. The results will inform adaptation of a one-hour workshop to educate prescribers about how to best prevent opioid diversion by their young adult patients.
Investigation of Opioid Exposure and Neurodevelopment (iOPEN)
Principal investigators Ashok Panigrahy, M.D., of UPMC Children’s Hospital of Pittsburgh and Pitt’s Department of Radiology, Beatriz Luna, Ph.D., of Pitt’s Department of Psychiatry, and Elizabeth E. Krans, M.D., M.Sc., of Pitt’s Department of Obstetrics, Gynecology & Reproductive Sciences and Magee-Womens Research Institute, received more than $200,000 as part of an effort with three other universities to design and plan for a large-scale study into the long-term effects of in-utero opioid exposure on neonatal brain development.
In-utero opioid exposure is associated with neonatal abstinence syndrome, which affects 6.5 of every 1,000 newborns. The UPMC and Pitt team will leverage their experience with the recruitment and retention of pregnant women with opioid use disorder, imaging fetal and newborn brains, and developmental cognitive neuroscience to conduct a longitudinal cohort study.
“It’s clear that a multi-pronged scientific approach is needed to reduce the risks of opioids, accelerate development of effective non-opioid therapies for pain and provide more flexible and effective options for treating addiction to opioids,” said NIH Director Francis S. Collins, M.D., Ph.D., who launched the initiative in early 2018 to improve treatments for chronic pain, curb the rates of opioid use disorder and overdose, and achieve long-term recovery from opioid addiction. “This unprecedented investment in the NIH HEAL Initiative demonstrates the commitment to reversing this devastating crisis.”
This research is funded by NIH grants 1U19AR076725-01, 1UG3AR076568-01, 1U24NS115708-01, 1U01DK123812-01, 1R01HL150432-01, 1UG3TR003090-01, 3R01DA037621-04, 3U01DA040213-05 and 1R34DA050290-01.