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Updated: May 6, 2026
A Preterm Rat Model for Pain Studies
Published on: February 9, 2024
Neonatal pain in very preterm infants: long-term effects on brain, neurodevelopment and pain reactivity
1Department of Pediatrics, University of British Columbia and Child & Family Research Institute, Vancouver, Canada; and School of Nursing and Midwifery, Queen's University Belfast, UK.
Insights
Repetitive procedural pain in the neonatal intensive care unit (NICU) can adversely affect brain development and stress systems in very preterm infants. Early pain management and parental interventions may offer brain protection.
Area of Science:
- Neonatal care
- Developmental neuroscience
- Pediatric pain research
Background:
- Early life adversity, including psychosocial stress and procedural pain, has known long-term effects.
- Preterm infants (24-32 weeks' gestational age) are particularly vulnerable to pain and stress due to physiological immaturity.
- The impact of neonatal intensive care unit (NICU) procedural pain on infant development is an emerging area of clinical research.
Purpose of the Study:
- To review clinical studies on the long-term effects of repeated procedural pain in the NICU.
- To examine the relationship between neonatal pain/stress and brain development, neurodevelopment, stress system programming, and pain sensitivity in very preterm infants.
- To highlight the importance of pain management and non-pharmacological interventions in the NICU.
Main Methods:
- Focus on clinical studies examining infants born very preterm (24-32 weeks' gestational age).
- Quantification of neonatal pain exposure based on the number of invasive and/or skin-breaking procedures during NICU hospitalization.
- Analysis of associations between early pain/stress and neurodevelopmental outcomes, stress system programming, and later pain sensitivity, considering confounding factors of prematurity.
Main Results:
- Emerging evidence indicates adverse impacts of neonatal pain/stress on the developing brain, neurodevelopment, and hypothalamic-pituitary-adrenal axis programming in immature infants.
- Early pain/stress may influence brain development, neurodevelopment, and stress-sensitive behaviors, especially in the most vulnerable neonates.
- No increased prevalence of pain syndromes was observed compared to full-term healthy individuals; confounding factors of prematurity require careful consideration.
Conclusions:
- Repeated procedural pain and stress in the NICU can negatively impact brain development and neurodevelopment in very preterm infants.
- Non-pharmacological interventions and parental involvement are crucial for reducing infant stress and may be brain-protective.
- Advocacy for effective pain management in the NICU is essential for humanitarian care and optimal infant outcomes.
Abstract:
Effects of early life psychosocial adversity have received a great deal of attention, such as maternal separation in experimental animal models and abuse/neglect in young humans. More recently, long-term effects of the physical stress of repetitive procedural pain have begun to be addressed in infants hospitalized in neonatal intensive care. Preterm infants are more sensitive to pain and stress, which cannot be distinguished in neonates. The focus of this review is clinical studies of long-term effects of repeated procedural pain-related stress in the neonatal intensive care unit (NICU) in relation to brain development, neurodevelopment, programming of stress systems, and later pain sensitivity in infants born very preterm (24-32 weeks' gestational age). Neonatal pain exposure has been quantified as the number of invasive and/or skin-breaking procedures during hospitalization in the NICU. Emerging studies provide convincing clinical evidence for an adverse impact of neonatal pain/stress in infants at a time of physiological immaturity, rapidly developing brain microstructure and networks, as well as programming of the hypothalamic-pituitary-adrenal axis. Currently it appears that early pain/stress may influence the developing brain and thereby neurodevelopment and stress-sensitive behaviors, particularly in the most immature neonates. However, there is no evidence for greater prevalence of pain syndromes compared to children and adults born healthy at full term. In addressing associations between pain/stress and outcomes, careful consideration of confounding clinical factors related to prematurity is essential. The need for pain management for humanitarian care is widely advocated. Non-pharmacological interventions to help parents reduce their infant's stress may be brain-protective.
