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Assistant Professor Rob Bonin Part of Team to Identify Drug that Alleviates Opioid Withdrawal
Assistant Professor Rob Bonin of the Leslie Dan Faculty of Pharmacy is part of a multi-institutional, interdisciplinary team that identified the cellular basis of opioid withdrawal and targeted this processes with an existing anti-gout drug to alleviate withdrawal in opioid-dependent rodents. The results of this study appeared in the prestigious journal Nature Medicine.
Dr. Bonin worked with researchers at the University of Calgary’s Faculty of Veterinary Medicine and Hotchkiss Brain Institute at the Cumming School of Medicine to make this discovery, which is leading to the development of a clinical trial at the Calgary Pain Clinic to translate these findings into new treatments for opioid withdrawal.
Through this project, the researchers identified pannexin-1 as an important target for opioid withdrawal. The activity of pannexin-1 on microglia, immune cells of the brain and spinal cord, was responsible for producing opioid withdrawal symptoms in rodent models.
While opioids like fentanyl and morphine are highly potent at managing pain, they are also difficult to stop using, as discontinuing opioids can result in severe withdrawal symptoms. As a result, many patients continue to use opioids long after they are no longer required, which both lowers their efficacy and has the potential to cause long-term problems.
Dr. Bonin worked with the team to show that opioid withdrawal increases the transmission of information between neurons in pain processing regions of the spinal cord, which likely contributes to the pain experienced during opioid withdrawal. This work revealed that microglia signal to neurons during opioid withdrawal via pannexin-1 to facilitate neuronal transmission. Preventing the activity of pannexin-1 through genetic deletion or with the anti-gout medication, probenecid, eliminated neuronal facilitation in the spinal cord during withdrawal, and also prevented withdrawal symptoms in animals.
Ultimately, this study advances our understanding of the causes of opioid withdrawal, and shows tremendous promise for the development of new treatments to prevent opioid withdrawal in patients.