RELATED STORY: Rita Allen Foundation Scholars Reveal Biological Forces That Underlie Responses to Change
Tuan Trang (Award in Pain Recipient) began his research career as an undergraduate at Queen’s University studying the effects of prenatal alcohol exposure. He also completed a Ph.D. in pharmacology and toxicology there, researching the spinal mechanisms of opioid analgesia with the goal of developing new pharmacological strategies for improving pain therapy. He pursued postdoctoral training as a Canadian Institutes of Health Research (CIHR) fellow in the laboratory of Dr. Michael Salter at the Hospital for Sick Children in Toronto. He has received a CIHR New Investigator Award, and young investigator awards from the Canadian Association for Neuroscience and Canadian Society for Pharmacology and Therapeutics. His research has been supported by grants from, in addition to the Rita Allen Foundation, the CIHR, the Natural Sciences and Engineering Research Council of Canada, a Vi Riddell Pain Grant from the University of Calgary and the Canada Foundation for Innovation.
Opioids are among the most powerful and widely prescribed drugs for treating pain. However, a major problem in terminating opioid pain therapy is the debilitating withdrawal syndrome that can plague chronic opioid users. The mechanisms involved in opioid withdrawal are poorly understood, and the limited clinical strategies for treating withdrawal are ineffective. Trang and his collaborators have identified the pannexin-1 (Panx1) channel as a novel therapeutic target for treating morphine withdrawal. They discovered that morphine treatment induces synaptic plasticity in spinal lamina I/II neurons, which manifests as long-term synaptic facilitation upon naloxone-precipitated morphine withdrawal. This synaptic facilitation is critically gated by activation of Panx1 channels expressed on microglia. Pharmacologically blocking Panx1, or genetically ablating this channel specifically from microglia, blocked spinal synaptic facilitation and alleviated the behavioral sequelae of morphine withdrawal. Their findings together reveal a novel mechanism by which microglia signal through Panx1 to produce the cellular and behavioral corollary of withdrawal. Thus, targeting Panx1 represents a potential novel therapeutic approach for treating the symptoms of opioid withdrawal. Trang and his team are moving these discoveries into the clinic by building on the utility of probenecid as a unique and practical therapy for the management of opioid withdrawal. In a pilot clinical trial, they will test whether probenecid alleviates opioid withdrawal in patients undergoing opioid tapering, a systematic and gradual approach intended to reduce or discontinue opioid use.