The Neural Basis of Opioid-induced Respiratory Depression

2020 Seed Grant
Sung Han, Ph.D.
Salk Institute for Biological Studies

Opioids are the most commonly used and most effective analgesics, and are the first line of defense against acute and severe pain. However, this dramatic ability to mitigate pain comes with many side effects. These include constipation, nausea, sedation, dizziness, respiratory depression, dependence, and addiction. Among these, respiratory depression is the major drier of death by opioid overdose. According to the Center for Disease Control (CDC), nearly 47,000 people died in 2018 by opioid-induced respiratory depression (OIRD) in the United States, and the death rate is rising rapidly due to increased misuse and addiction to both prescription and illicit opioids. Thus, the US is currently experiencing a serious national public health crisis that is also taking a toll on social economic welfare. Despite these dire numbers, research elucidating the neural mechanisms of OIRD, which could identify therapeutic targets, is lacking. Animal studies have shown that OIRD is mediated by the µ-opioid receptor (MOR), however the neural circuits and brain regions responsible for OIRD have not yet been identified. The proposed research aims to dissect the neural circuits that mediate OIRD using the cutting-edge molecular, physiological, behavioral, and imaging techniques. Successful completion of the proposed research will provide neural circuit-based understanding of OIRD, and provide important insights toward developing therapeutic interventions to prevent OIRD.

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