Periodic hypoxia, intermittent pain, and caffeine in male and female neonatal rats: corticosterone, insulin resistance, and hepatic gene expression. Am J Physiol Regul Integr Comp Physiol 2023 Jun 01;324(6):R708-R719
Date
03/14/2023Pubmed ID
36912474DOI
10.1152/ajpregu.00316.2022Scopus ID
2-s2.0-85159739229 (requires institutional sign-in at Scopus site)Abstract
Preterm infants experience multiple stressors including periodic neonatal hypoxia, maternal/caregiver separation, and acute pain from clinical procedures. Although neonatal hypoxia or interventional pain are associated with sexually dimorphic effects that may last into adulthood, the interaction of these common preterm stressors and caffeine pretreatment remains unknown. We hypothesize that an interaction of acute neonatal hypoxia, isolation, and pain modeling the experience of the preterm infant will augment the acute stress response and that caffeine routinely given to preterm infants will alter this response. Male and female rat pups were isolated and exposed to six cycles of periodic hypoxia (10% O2) or normoxia (room air control) and/or intermittent pain by administering needle pricks (or touch control) to the paw on postnatal (PD) days 1-4. An additional set of rat pups was pretreated with caffeine citrate (80 mg/kg ip) and studied on PD1. Plasma corticosterone, fasting glucose, and insulin were measured to calculate homeostatic model assessment for insulin resistance (HOMA-IR) (index of insulin resistance). Glucocorticoid-, insulin-, and caffeine-sensitive gene mRNAs were analyzed in the PD1 liver and hypothalamus to evaluate downstream markers of glucocorticoid action. Acute pain with periodic hypoxia led to a large increase in plasma corticosterone, which was attenuated by pretreatment with caffeine. Pain with periodic hypoxia led to a 10-fold increase in hepatic Per1 mRNA expression in males, which was attenuated with caffeine. The augmentation of corticosterone and HOMA-IR at PD1 after periodic hypoxia with pain suggests early intervention to attenuate the stress response may mitigate the programming effects of neonatal stress.
Author List
Gehrand AL, Phillips JM, Raff HAuthor
Hershel Raff PhD Professor in the Academic Affairs department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Acute PainAdrenocorticotropic Hormone
Animals
Animals, Newborn
Caffeine
Corticosterone
Female
Gene Expression
Glucocorticoids
Humans
Hypothalamo-Hypophyseal System
Hypoxia
Infant, Newborn
Infant, Premature
Insulin
Insulin Resistance
Liver
Male
Rats
Rats, Sprague-Dawley
