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Updated: Jun 16, 2026
A Preterm Rat Model for Pain Studies
Published on: February 9, 2024
Physiological correlates of pain in preterm infants: evidence from a meta-analytic approach
Jianhua Liao1, Ping Xiong1, Yingchao Tan1
1Neonatal and Pediatric Intensive Care Unit, Women and Children's Hospital, Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China.
Insights
Preterm infants show significant physiological changes in heart rate, cortisol, and oxygenation during painful procedures. These objective indicators can improve pain assessment and management in neonatal intensive care.
Area of Science:
- Neonatal Medicine
- Pain Physiology
- Biomarkers
Background:
- Preterm infants in neonatal intensive care experience frequent painful procedures.
- Understanding their physiological pain responses and reliable biomarkers is crucial but incomplete.
- This meta-analysis sought objective indicators of pain in preterm infants.
Purpose of the Study:
- To synthesize evidence on physiological correlates of pain in preterm infants.
- To identify consistent and objective indicators of procedural pain.
- To inform improved pain assessment and management strategies.
Main Methods:
- Systematic literature search across major databases (PubMed, Scopus, Web of Science, Embase, CINAHL) from January 2017 to December 2025.
- Inclusion of randomized controlled trials, cohort, and observational studies on preterm infants' physiological responses to procedural pain.
- Analysis using random-effects models with heterogeneity assessed by the I² statistic.
Main Results:
- Fifteen studies with 1,273 preterm infants were included.
- Procedural pain significantly increased heart rate and cortisol levels.
- Pain decreased heart rate variability, oxygen saturation, melatonin, and cerebral oxygenation.
Conclusions:
- Procedural pain in preterm infants triggers significant physiological responses across multiple systems.
- Integrating objective physiological indicators can enhance neonatal pain assessment.
- Improved pain recognition and management may support better neurodevelopmental outcomes for preterm infants.
Background:
Preterm infants are frequently exposed to painful procedures during neonatal intensive care, yet their physiological capacity to respond to pain and the reliability of related biomarkers remain incompletely understood. This meta-analysis aimed to synthesize evidence on physiological correlates of pain in preterm infants to identify consistent objective indicators of pain.
Methods:
A systematic search of PubMed, Scopus, Web of Science, Embase, and CINAHL was conducted for studies published between January 2017 and December 2025. Randomized controlled trials, cohort, and observational studies assessing physiological responses to procedural pain in preterm infants were included. Data were analyzed using random-effects models, and heterogeneity was assessed with the I² statistic.
Results:
Fifteen studies involving 1,273 preterm infants met the inclusion criteria. Painful procedures induced significant increases in heart rate (mean difference +12.6 bpm, p < 0.001) and cortisol levels (SMD = + 0.68, p < 0.01), alongside decreases in heart rate variability (SMD = -0.81, p < 0.001), oxygen saturation (-4.3%, p < 0.01), melatonin (SMD = -0.54, p < 0.05), and cerebral oxygenation (-8.5%, p < 0.001). Subgroup analyses showed the strongest effects in cardiorespiratory parameters (SMD = 0.91). No significant publication bias was detected.
Conclusion:
Procedural pain in preterm infants elicits robust physiological responses across autonomic, endocrine, and neurophysiological domains. Integrating these objective indicators into neonatal pain assessment may enhance early recognition and improve pain management practices, ultimately supporting better neurodevelopmental outcomes.
