Related Experiment Video
Updated: May 31, 2026
A Preterm Rat Model for Pain Studies
Published on: February 9, 2024
Neonatal inflammatory pain increases hippocampal neurogenesis in rat pups
Ana Teresa F S Leslie1, Katherine G Akers, Alonso Martinez-Canabal
1Departamento de Pediatria, Universidade Federal de São Paulo, São Paulo, Brazil.
Insights
Neonatal pain in rat pups can increase hippocampal neurogenesis, particularly when experienced later in the neonatal period. These findings suggest early pain exposure may influence brain development and future behavior.
Area of Science:
- Neuroscience
- Developmental Biology
- Pain Research
Background:
- Preterm infants experience significant pain in neonatal intensive care units.
- Early painful experiences may impact neurodevelopment.
- The hippocampus, crucial for learning and memory, is sensitive to early life events.
Purpose of the Study:
- To investigate the effect of neonatal pain on hippocampal neurogenesis in an animal model.
- To determine if the timing of neonatal pain exposure influences its impact on neuronal generation.
Main Methods:
- Rat pups received intraplantar injections of complete Freund's adjuvant (CFA), a painful inflammatory agent, on postnatal day 1 (P1) or postnatal day 8 (P8).
- Bromodeoxyuridine (BrdU) labeling was used to assess cell proliferation.
- Doublecortin (DCX) expression was analyzed to evaluate the generation of new neurons.
- Animals were sacrificed on postnatal day 22 (P22) for analysis.
Main Results:
- Rat pups injected with CFA on P8 showed increased BrdU-labeled cells in the dentate gyrus.
- A higher density of doublecortin (DCX)-expressing cells was observed in the subgranular zone of the dentate gyrus in P8-injected pups.
- No significant changes in BrdU-labeling or DCX expression were found in pups injected with CFA on P1.
Conclusions:
- Neonatal pain exposure can enhance hippocampal neurogenesis.
- The timing of pain exposure is critical, with later neonatal pain (P8) having a significant effect.
- These findings suggest that early painful experiences may shape brain development and potentially influence behavioral outcomes.
Abstract:
Preterm infants undergo several painful procedures during their stay in neonatal intensive care units. Previous studies suggest that early painful experiences may have an impact on brain development. Here, we used an animal model to investigate the effect of neonatal pain on the generation of new neurons in the dentate gyrus region of the hippocampus. Rat pups received intraplantar injections of complete Freund's adjuvant (CFA), a painful inflammatory agent, on either P1 or P8 and were sacrificed on P22. We found that rat pups injected with CFA on P8 had more BrdU-labeled cells and a higher density of cells expressing doublecortin (DCX) in the subgranular zone of the dentate gyrus. No change in BrdU-labeling or DCX expression was observed in pups injected with CFA on P1. These findings indicate that neonatal pain can increase hippocampal neurogenesis, suggesting that early painful experiences may shape brain development and thereby influence behavioral outcome.
