Neural basis of opioid-induced respiratory depression and its rescue
Shijia Liu, Dong‐Il Kim, Tae Gyu Oh, Gerald M. Pao, Jong‐Hyun Kim, Richard D. Palmiter, Matthew R. Banghart, Kuo‐Fen Lee, Ronald M. Evans, Sung Han
Abstract
Significance Opioid-induced respiratory depression (OIRD) is the direct cause of death from opioid overdose, which accounts for the current global opioid crisis. Here, we report that neurons expressing the μ-opioid receptors in the lateral parabrachial nucleus of the pontine respiratory group are necessary and sufficient for the pathogenesis of OIRD. Activating these neurons through endogenous or artificial G protein–coupled receptor signaling pathways rescues OIRD in intact mice, suggesting its therapeutic utility in OIRD patients.
Topics & Concepts
OpioidLateral parabrachial nucleusRespiratory systemDepression (economics)NeuroscienceEndogenous opioidParabrachial NucleusMedicineReceptorOpioid peptidePharmacologyEndogenyPathogenesisCentral nervous systemBiologyInternal medicineEconomicsMacroeconomicsNeuroscience of respiration and sleepNeuropeptides and Animal PhysiologyNeuroendocrine regulation and behavior