Related Experiment Video
Updated: May 24, 2026

A Preterm Rat Model for Pain Studies
Published on: February 9, 2024
Does the neonatal clinical risk for illness severity influence pain reactivity and recovery in preterm infants?
B O Valeri1, C M Gaspardo, F E Martinez
1Department of Neurosciences and Behavior, University of São Paulo, São Paulo, Brazil.
Insights
High clinical risk preterm infants show greater pain reactivity and physiological responses during and after painful procedures. This highlights the central nervous system
Area of Science:
- Neonatal Medicine
- Developmental Neuroscience
- Pediatric Pain Research
Background:
- Preterm infant pain reactivity and recovery in the neonatal period are indicators of central nervous system (CNS) regulatory capacity.
- Understanding these responses is crucial for neurodevelopmental outcomes.
Purpose of the Study:
- To investigate the impact of neonatal clinical risk severity on the biobehavioral pain responses of preterm infants.
- To assess how illness severity influences pain reactivity and recovery patterns.
Main Methods:
- Fifty-two preterm infants were categorized into low clinical risk (LCr, CRIB <4) and high clinical risk (HCr, CRIB ≥4) groups.
- Pain reactivity was evaluated during blood collection across five phases: baseline, antisepsis, puncture, recovery-dressing, and recovery-resting.
- Behavioral pain was measured using the Neonatal Facial Coding System (NFCS) and Sleep-Wake States Scale (SWS), with continuous heart rate monitoring.
Main Results:
- The HCr group exhibited significantly higher SWS scores from baseline to puncture compared to the LCr group.
- HCr infants showed elevated mean and minimum heart rates during the recovery-resting phase.
- Higher minimum heart rates were observed in the HCr group across all measured phases.
Conclusions:
- Preterm infants with high neonatal clinical risk display heightened arousal during painful procedures like puncture.
- These infants also demonstrate increased physiological reactivity during the recovery phase post-procedure.
- Neonatal illness severity is a significant factor influencing pain biobehavioral responses in preterm infants.
Background:
The biobehavioural pain reactivity and recovery of preterm infants in the neonatal period may reflect the capacity of the central nervous system to regulate neurobiological development.
Objective:
The aim of the present study was to analyse the influence of the neonatal clinical risk for illness severity on biobehavioural pain reactivity in preterm infants.
Methods:
Fifty-two preterm infants were allocated into two groups according to neonatal severity of illness, as measured by the Clinical Risk Index for Babies (CRIB). The low clinical risk (LCr) group included 30 neonates with CRIB scores <4, and the high clinical risk (HCr) group included 22 neonates with CRIB scores ≥4. Pain reactivity was assessed during a blood collection, which was divided into five phases (baseline, antisepsis, puncture, recovery-dressing and recovery-resting). Behavioral pain reactivity was measured using the scores, and magnitude of responses in Neonatal Facial Coding System (NFCS) and Sleep-Wake States Scale (SWS). The heart rate was continuously recorded.
Results:
The HCr demonstrated a higher magnitude of response on the SWS score from the baseline to the puncture phase than the LCr. Also, the HCr exhibited a higher mean heart rate and minimum heart rate than the LCr in the recovery-resting phase. In addition, the HCr exhibited a higher minimum heart rate from the baseline to the recovery-resting phase than the LCr.
Conclusion:
The infants exhibiting a high neonatal clinical risk showed high arousal during the puncture procedure and higher physiological reactivity in the recovery phase.

