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Updated: Oct 15, 2026

A Preterm Rat Model for Pain Studies
Published on: February 9, 2024
Behavior, pain perception, and the extremely low-birth weight survivor
1Department of Paediatrics, University of British Columbia, B.C.'s Children's Hospital, Vancouver, Canada. mwhitfield@cw.bc.ca
Insights
Neonatal pain and stress can negatively impact infant neurodevelopment. While acute pain assessment is challenging, prolonged pain may cause lasting autonomic changes and later learning or behavior issues.
Area of Science:
- Neonatal care
- Neuroscience
- Developmental pediatrics
Background:
- Neonatal pain and stress are significant concerns with potential long-term neurodevelopmental consequences.
- Assessing acute pain in newborns is difficult, and chronic or repeated pain is common in clinical settings.
Purpose of the Study:
- To review the literature on neonatal pain responses, its short- and long-term effects, and behavioral outcomes.
- To discuss the clinical implications of pain and its management in newborns, particularly extremely low birth weight (ELBW) infants.
Main Methods:
- Literature review of studies on neonatal pain perception, neurodevelopmental outcomes, and pain management strategies.
- Analysis of evidence regarding the effects of pain and analgesics (e.g., morphine) on the developing central nervous system.
Main Results:
- Repeated or prolonged untreated neonatal pain can lead to lasting changes in autonomic arousal and may contribute to later attention, learning, and behavior problems.
- While acute pain reactivity may not show significant long-term clinical differences, chronic pain exposure can have detrimental effects.
- Judicious use of morphine for procedures like mechanical ventilation may improve autonomic responses, but overuse of sedatives carries risks.
Conclusions:
- Early pain exposure in newborns, especially chronic or untreated pain, poses risks to long-term neurodevelopment and behavior.
- Distinguishing between stress and pain is crucial, as is the judicious use of analgesics to avoid adverse effects on the developing brain.
- Effective pain management in neonatal intensive care is vital for improving long-term outcomes in high-risk infants.
Abstract:
This article explores the literature concerning responses to pain of both premature and term-born newborn infants, the evidence for short-term and long-term effects of pain, and behavioral sequelae in individuals who have experienced repeated early pain in neonatal life as they mature. There is no doubt that pain causes stress in babies and this in turn may adversely affect long-term neurodevelopmental outcome. Although there are methods for assessing dimensions of acute reactivity to pain in an experimental setting, there are no very good measures available at the present time that can be used clinically. In the clinical setting repeated or chronic pain is more likely the norm rather than infrequent discrete noxious stimuli of the sort that can be readily studied. The wind-up phenomenon suggests that, exposed to a cascade of procedures as happens with clustering of care in the clinical setting in an attempt to provide periods of rest for stressed babies, an infant may in fact perceive procedures that are not normally viewed as noxious, as pain. Pain exposure during lifesaving intensive medical care of ELBW neonates may also affect subsequent reactivity to pain in the neonatal period, but behavioral differences are probably not likely to be clinically significant in the long term. Prolonged and repeated untreated pain in the newborn period, however, may produce a relatively permanent shift in basal autonomic arousal related to prior NICU pain experience, which may have long-term sequelae. In the long run, the most significant clinical effects of early pain exposure may be on neurodevelopment, contributing to later attention, learning, and behavior problems in these vulnerable children. Although there is considerable evidence to support a variety of adverse effects of early pain, there is less information about the long-term effects of opiates and benzodiazepines on the developing central nervous system. Current evidence reviewed suggests that judicious use of morphine for adjustment to mechanical ventilation may ameliorate the altered autonomic response. It may be very important, however, to distinguish stress from pain. Animal evidence suggests that the neonatal brain is affected differently when exposed to morphine administered in the absence of pain than in the presence of pain. Pain control may be important for many reasons but overuse of morphine or benzodiazepines may have undesirable long-term effects. This is a rapidly evolving area of knowledge of clear relevance to clinical management likely to affect long-term outcomes of high-risk children.

