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Phenotypes of remodeling in respiratory physiology due to chronic opioid use
Author(s) -
Szujewski Caroline,
Browe Brigitte,
Nwakudu Chinwendu,
Sharp Williard,
Garcia Alfredo
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.04558
Subject(s) - fentanyl , medicine , opioid , respiratory system , anesthesia , respiration , control of respiration , analgesic , chronic pain , receptor , physical therapy , anatomy
Deaths related to synthetic opioids have increased six‐fold over the past 20 years. In comparison to the expansive foundation of literature investigating circuit and cellular level mechanisms involved with acute opioid induced respiratory depression (OIRD), very little is known about how chronic opioid use remodels respiration. Similarly, the understanding of tolerance to the euphoric and analgesic effects of opioids has been well studied, yet tolerance to the respiratory side effects of chronic opioid use has been largely ignored. One reason that this gap in knowledge may exist is that the rates of tolerance to the analgesic and euphoric effects of opioids appear to emerge faster than respiratory tolerance to opioids. The goal of this ongoing work is to investigate the mechanisms by which chronic fentanyl use influences the control of breathing and the development of tolerance to its depressive respiratory effects. Here, we introduce an adult mouse model of chronic opioid use. In this model, the synthetic opioid, fentanyl (0.7 mg/kg) was administered for up to ten days. Breathing was assessed prior to, during and after OIRD using unrestrained whole body plethysmography. Our preliminary findings indicate that after five days of fentanyl administration, the magnitude of OIRD is approximately 50% less (n=5) as compared to ORID during the first day of fentanyl. Moreover, assessing the hypoxic chemoreflex after five days of chronic fentanyl treatment reveals that the hypoxic ventilatory response (outside of the window of OIRD). In 2 of 5 subjects, pronounced periodic breathing emerged during baseline conditions after the fifth day of fentanyl administration. These results are consistent with phenotypes observed in individuals who chronically use opioids and/or receive treatment for chronic opioid use and suggest that chronic fentanyl use perturbs respiratory control outside of the immediate window of OIRD. Thus, our model can be used to examine the mechanisms that that drive pharmacodynamic changes to opioids and promote respiratory‐related morbidities associated with chronic fentanyl use.