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Opioids depress breathing through two small brainstem sites.

ABSTRACT: The rates of opioid overdose in the United States quadrupled between 1999 and 2017, reaching a staggering 130 deaths per day. This health epidemic demands innovative solutions that require uncovering the key brain areas and cell types mediating the cause of overdose- opioid-induced respiratory depression. Here, we identify two primary changes to murine breathing after administering opioids. These changes implicate the brainstem's breathing circuitry which we confirm by locally eliminating the µ-Opioid receptor. We find the critical brain site is the preBötzinger Complex, where the breathing rhythm originates, and use genetic tools to reveal that just 70-140 neurons in this region are responsible for its sensitivity to opioids. Future characterization of these neurons may lead to novel therapies that prevent respiratory depression while sparing analgesia.

SUBMITTER: Bachmutsky I

PROVIDER: S-EPMC7077984 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Opioids depress breathing through two small brainstem sites.

Bachmutsky Iris I Wei Xin Paul XP Kish Eszter E Yackle Kevin K

eLife 20200219

The rates of opioid overdose in the United States quadrupled between 1999 and 2017, reaching a staggering 130 deaths per day. This health epidemic demands innovative solutions that require uncovering the key brain areas and cell types mediating the cause of overdose- opioid-induced respiratory depression. Here, we identify two primary changes to murine breathing after administering opioids. These changes implicate the brainstem's breathing circuitry which we confirm by locally eliminating the µ- ...[more]

PMID: 32073401

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