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Updated: Aug 25, 2025
A Preterm Rat Model for Pain Studies
Published on: February 9, 2024
Repeated Sevoflurane Exposure in Neonatal Rats Enhances the Sensitivity to Pain and Traumatic Stress Later in
Ben-Zhen Chen1,2, Li-Hua Jiang3, Wenqin Zhou4
1Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
Insights
Neonatal sevoflurane exposure increases pain sensitivity and stress response in juvenile rats. This is linked to changes in GABAergic signaling, which can be modulated by bumetanide.
Area of Science:
- Neuroscience
- Anesthesiology
- Developmental Biology
Background:
- Neonatal exposure to anesthetics like sevoflurane may cause long-term neurodevelopmental issues.
- Previous studies suggest sevoflurane exposure is linked to neuroendocrine dysregulation.
Purpose of the Study:
- To investigate if repeated neonatal sevoflurane exposure enhances pain sensitivity and stress response in juvenile rats.
- To determine if neonatal brain depolarizing gamma-aminobutyric acid type A receptor (GABAAR) activity mediates these effects.
Main Methods:
- Postnatal day 6 Sprague-Dawley male rats were exposed to sevoflurane or vehicle.
- Some rats received bumetanide, a NKCC1 inhibitor, prior to sevoflurane exposure.
- Pain sensitivity (PWTL) and corticosterone levels after conditioned fear traumatic stress (CFTS) were assessed.
Main Results:
- Sevoflurane exposure reduced paw withdrawal thermal latency (PWTL) in juvenile rats.
- Sevoflurane-exposed rats showed elevated corticosterone levels after CFTS.
- The NKCC1/KCC2 mRNA ratio increased post-sevoflurane exposure, an effect reduced by bumetanide.
Conclusions:
- Repeated neonatal sevoflurane exposure exacerbates pain sensitivity and acute traumatic stress response in juvenile rats.
- Neonatal brain depolarizing GABAAR activity plays a role in mediating these sevoflurane-induced abnormalities.
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 (GABAAR) 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 GABAAR activity is involved in mediating these abnormalities.
