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Hypercapnic acidosis acts on two opposing mechanisms to modulate the efficacy of opioid neuromodulation of inspiratory drive
Author(s) -
Garcia Alfredo J,
Andreson Tatiana M,
Ramirez JanMarino
Publication year - 2016
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.30.1_supplement.987.9
Subject(s) - damgo , opioid , neuromodulation , neuroscience , enkephalin , respiratory system , rhythm , anesthesia , medicine , pharmacology , psychology , central nervous system , receptor
Exogenous neuromodulation of central respiratory networks by opioids disrupts the normal orchestration of central respiratory control and thereby depresses the drive to breathe. Hypercapnic acidosis (HA) is a well‐recognized avenue that enhances central respiratory drive. Using the in vitro rhythmic slice preparation, this ongoing study examines how HA influences opioid neuromodulation of inspiratory drive from the preBötzinger complex (preBötC). In the majority of experiments, rhythms appeared to be HA‐insensitive, yet in a minority of cases, HA stimulated the frequency of the preBötC rhythm. When HA stimulated rhythmogenesis, the ability for 25nM DAMGO to suppress the preBötC was attenuated. However, in HA‐insensitive rhythms, HA augmented the suppressive action of 25nM DAMGO on rhythmogenesis. Enhancing inspiratory drive with 2μM norepinephrine stimulated the rhythm and caused a right‐shift in the dose response of rhythmogenesis to DAMGO, but did not appear to affect the ability for HA to augment the suppressive action of the opioid. These findings suggest that HA acts on two opposing arms of a push‐pull mechanism important to orchestrating opioid neuromodulation in the respiratory network. Thus, when intact, such a mechanism may be important to dynamically control respiratory drive and if imbalanced, this mechanism may perpetuate respiratory instability during opioid overdose and/or in other conditions such as neonatal abstinence syndrome.