Abhishek Guha, Ph.D., and Peter H. King, M.D.UAB researchers Abhishek Guha, Ph.D., Researcher V, and Peter H. King, M.D., professor, both in the Department of Neurology, have received a multi-PI R01 research award from the NIH's National Institute of Neurological Disorders and Stroke to investigate novel molecular mechanisms underlying the development and persistence of pain after acute peripheral injury. The project, titled "Role of RNA Regulator Tristetraprolin in mitigating pain responses after peripheral injury through suppression of pro-inflammatory mediators," totals approximately $2.4 million in funding.
Tristetraprolin (TTP) is an RNA-binding protein that binds to and suppresses messenger RNAs (mRNAs) of key proinflammatory and nociceptive factors driving the development and persistence of neuropathic pain after injury. The project will investigate mechanisms of how TTP suppresses these mRNAs and approaches to increase its activity pharmacologically to block the development of pain.
“Chronic pain and neuroinflammation affect millions of people, yet many of the molecular mechanisms that sustain these conditions remain poorly understood,” Guha said. “Our goal is to determine how TTP regulates inflammatory and pain-related pathways and to identify molecular mechanisms that may ultimately support the development of more effective, non-opioid-based treatments. This is a novel area of investigation in pain research and has the promise for developing new treatments.”
The research team will investigate how genetic and pharmacological activation of TTP affects inflammatory signaling involved in the pain plasticity. The project will focus on molecular interactions that connect RNA regulation with the activation of pain pathways and neuroimmune responses. Using cellular, molecular, animal-model, and/or single-cell transcriptomic approaches, the investigators will examine TTP-dependent changes in mRNA and protein levels and determine how these changes contribute to inflammation and pain sensitivity.
As a senior clinician-scientist and co-principal investigator, King will provide both basic science and clinical expertise to ensure that the findings are expeditiously translated to patients.
“I see many patients with chronic neuropathic pain who do not respond to treatment and often become dependent on opioids," King said. “By combining mechanistic laboratory research with clinical expertise, this project will help clarify mechanisms of pain development and persistence and identify novel non-opioid treatment strategies."
He added, "This award recognizes the importance of understanding pain at a very basic level by merging RNA biology, neuroscience, and neuroinflammation to address an important health challenge.”
Robert E. Sorge, Ph.D., professor in the UAB Department of Psychology, and Daniel Tyrrell, Ph.D., assistant professor in the Department of Pathology, will serve as co-investigators on the project. They will assist with pain-related behavioral studies and single-cell transcriptomic studies, respectively.
“This project builds on our long-standing interest in RNA regulation and its role in CNS disease,” Guha said. “We are grateful to the Department of Veterans Affairs and the UAB Heersink School of Medicine, which provided the necessary support to achieve this award.”