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other·pediatrics, neurology, pulmonology, preclinical research, biomedical research·PMC10060555

Maternal opioids age-dependently impair neonatal respiratory control networks

Frontiers in Physiology · 6 authors, 2 centres

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TL;DR

This preclinical study used isolated neonatal rat respiratory networks to show that maternal opioid exposure directly impairs the development and function of central respiratory control circuits in an age-dependent manner.

Full summary

820 CHARS

The study used isolated central respiratory networks from neonatal rats born to opioid-exposed dams to investigate direct effects on respiratory control. Fictive respiratory activity was recorded from progressively isolated preparations (brainstem+spinal cord and medullary slices). These deficits were attributed to lingering opioids within the networks immediately after birth and lasting alterations to respiratory pattern. The respiratory networks also showed a blunted response to exogenous opioids, which correlated with changes in mu-opioid receptor expression in the preBötzinger Complex. The study concludes that maternal opioids directly impair the maturation and function of neonatal respiratory control networks, which likely contributes to breathing instability in infants with Neonatal Abstinence Syndrome.

STUDY TYPE

other

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pediatrics

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AI pipeline

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100% · A

ORIGINAL PAPER

PMC10060555

Maternal opioids age-dependently impair neonatal respiratory control networks

Frontiers in Physiology

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ABSTRACT

Infants exposed to opioids in utero are an increasing clinical population and these infants are often diagnosed with Neonatal Abstinence Syndrome (NAS). Infants with NAS have diverse negative health consequences, including respiratory distress. However, many factors contribute to NAS, confounding the ability to understand how maternal opioids directly impact the neonatal respiratory system. Breathing is controlled centrally by respiratory networks in the brainstem and spinal cord, but the impact of maternal opioids on developing perinatal respiratory networks has not been studied. Using progressively more isolated respiratory network circuitry, we tested the hypothesis that maternal opioids directly impair neonatal central respiratory control networks. Fictive respiratory-related motor activity from isolated central respiratory networks was age-dependently impaired in neonates after maternal opioids within more complete respiratory networks (brainstem and spinal cords), but unaffected in more isolated networks (medullary slices containing the preBötzinger Complex). These deficits were due, in part, to lingering opioids within neonatal respiratory control networks immediately after birth and involved lasting impairments to respiratory pattern. Since opioids are routinely given to infants with NAS to curb withdrawal symptoms and our previous work demonstrated acute blunting of opioid-induced respiratory depression in neonatal breathing, we further tested the responses of isolated networks to exogenous opioids. Isolated respiratory control networks also demonstrated age-dependent blunted responses to exogenous opioids that correlated with changes in opioid receptor expression within a primary respiratory rhythm generating region, the preBötzinger Complex. Thus, maternal opioids age-dependently impair neonatal central respiratory control and responses to exogenous opioids, suggesting central respiratory impairments contribute to neonatal breathing destabilization after maternal opioids and likely contribute to respiratory distress in infants with NAS. These studies represent a significant advancement of our understanding of the complex effects of maternal opioids, even late in gestation, contributing to neonatal breathing deficits, necessary first steps in developing novel therapeutics to support breathing in infants with NAS.

CITATION EXPORT

Sarah A. Beyeler, Robyn Naidoo, Nina R. Morrison et al.. Maternal opioids age-dependently impair neonatal respiratory control networks. Frontiers in Physiology. (2023). https://doi.org/10.3389/fphys.2023.1109754

AUTHORS

6 · 2 CENTRES

Sarah A. Beyeler, Robyn Naidoo, Nina R. Morrison, Emilee A. McDonald, David Albarrán, Adrianne G. Huxtable

1 Department of Biology, Institute of Neuroscience, University of Oregon, Eugene, OR, United States
2 Department of Human Physiology, University of Oregon, Eugene, OR, United States