Repeated Sevoflurane Exposure in Neonatal Rats Enhances the Sensitivity to Pain and Traumatic Stress Later in Juvenile Life

Ben-Zhen Chen; Li-Hua Jiang; Wenqin Zhou; Yu-Chao Shang; Fang Li; Bin Liu

doi:10.2147/JPR.S365253

Repeated Sevoflurane Exposure in Neonatal Rats Enhances the Sensitivity to Pain and Traumatic Stress Later in Juvenile Life

J Pain Res. 2022 Oct 12:15:3171-3178. doi: 10.2147/JPR.S365253. eCollection 2022.

Authors

Ben-Zhen Chen^#^{1

2}, Li-Hua Jiang^#³, Wenqin Zhou⁴, Yu-Chao Shang⁴, Fang Li¹, Bin Liu¹

Affiliations

¹ Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
² Department of Anesthesiology, Sichuan Provincial Women's and Children's Hospital, Chengdu, People's Republic of China.
³ Department of Operating Room Nursing, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, People's Republic of China.
⁴ Department of Anesthesiology, West China Second University Hospital, Sichuan University, Chengdu, People's Republic of China.

^# Contributed equally.

Abstract

Purposeː: Sevoflurane exposure in the neonatal period of rodent animals was reported to be associated with neuroendocrine dysregulations later in life. We tested the hypothesis that repeated sevoflurane exposure in neonatal rats enhances the sensitivity to pain and acute traumatic stress response later in juvenile life and investigated whether the neonatal brain depolarizing γ-aminobutyric acid type A receptor (GABA_AR) activity is involved in mediating these abnormalities.

Methodsː: The postnatal 6 days (P6) Sprague-Dawley male rat pups pretreated with vehicle or the NKCC1 inhibitor, bumetanide, received sequential exposures to 2.1% sevoflurane exposure for 2 hours daily in 3 consecutive days.

Resultsː: The results showed that repeated exposures to sevoflurane in neonatal rats significantly reduced the paw withdrawal thermal latency (PWTL) at P9, P45. Repeated exposures to sevoflurane in neonatal rats did not significantly affect the basal secretion of serum corticosterone at juvenile period P45, whereas the level of corticosterone for neonatal sevoflurane-exposed rats at P45 was significantly higher than the CON group after subject to conditioned fear traumatic stress (CFTS). The resulting NKCC1/KCC2 mRNA ratio was significantly increased immediately after the neonatal rats received the last sevoflurane exposure, which was alleviated by pretreated with the NKCC1 inhibitor bumetanide.

Conclusionː: Repeated exposures to sevoflurane in neonatal rats enhanced the sensitivity to pain and acute traumatic stress response in juvenile life. The neonatal brain depolarizing GABA_AR activity is involved in mediating these abnormalities.

Keywords: conditioned fear traumatic stress; exposure; neonatal; paw withdrawal thermal latency; sevoflurane.

Grants and funding

This work was supported by the grants from the National Natural Science Foundation of China (Nos. 81701090) and Key research project of Health Commission of Sichuan Province (Grant Number: 19ZD009).