Findings Suggest New Target for Mediating Tolerance and Addiction

A study conducted by researchers from Georgia State University and Emory University reports the discovery of a brain mechanism that may be an effective therapeutic target for forestalling opioid tolerance and addiction. The study linked morphine tolerance to an inflammatory response in the brain caused by the release of cytokines. Experiments in rat models demonstrated that blocking a specific cytokine reduced morphine tolerance and enabled a 50% reduction in morphine dosage to achieve the same level of pain management. Lead author Lori Eidson, a graduate student in the laboratory of Dr. Anne Murphy in the Neuroscience Institute of Georgia State commented “These results have important clinical implications for the treatment of pain and also addiction. Until now, the precise underlying mechanism for opioid tolerance and its prevention have remained unknown.” The findings appear in the Nature journal Neuropsychopharmacology.

Opioid tolerance and the potential for addiction is a significant burden associated with pain management, with morphine tolerance affecting long-term opioid therapy for about 60% of patients.  Immune signaling contributes to the decreased efficacy of opioids, and the study team demonstrated that Toll-like receptor 4 (TLR4)-mediated neuroinflammation in the periaqueductal gray (PAG) drives tolerance. In the rat experiments, the administration of a drug that blocked the immune response was shown to eliminate morphine tolerance. According to the authors, the findings suggest a novel pharmacological target for the prevention of opioid-induced immune signaling, tolerance, and addiction. Read more about the discovery here. The journal abstract may be read here.


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