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Updated: Mar 21, 2026

Electrophysiological Measurement of Noxious-evoked Brain Activity in Neonates Using a Flat-tip Probe Coupled to Electroencephalography
Published on: November 29, 2017
The cortical response to a noxious procedure changes over time in preterm infants
Stefano Bembich1, Francesca Marrazzo, Alice Barini
1Division of Neonatology, Institute for Maternal and Child Health-IRCCS "Burlo Garofolo," Trieste, Italy.
Insights
Preterm infants show developing brain responses to pain. Cortical activation to heel pricks increases with brain maturation but decreases with repeated painful experiences.
Area of Science:
- Neuroscience
- Developmental Biology
- Neonatology
Background:
- Preterm infants experience repeated painful procedures during hospitalization.
- Understanding the developing brain's response to pain is crucial for pain management.
Purpose of the Study:
- To investigate changes in cortical response to repeated noxious stimuli in preterm infants.
- To explore the influence of central nervous system maturation and cumulative pain exposure on these responses.
Main Methods:
- Utilized multichannel near-infrared spectroscopy (NIRS) to measure cortical oxy-haemoglobin (HbO2) changes.
- Assessed 16 preterm infants (29-36 weeks postmenstrual age) during weekly heel-prick procedures.
- Analyzed the relationship between postmenstrual age (PMA), number of heel pricks, and cortical activation magnitude.
Main Results:
- Observed bilateral nociceptive event-related activation in the posterior frontal cortex.
- Found a significant positive correlation between increasing postmenstrual age and increased posterior frontal cortical activation (P < 0.001).
- Demonstrated an inverse relationship between the number of noxious events and the degree of cortical activation (P < 0.002).
Conclusions:
- Preterm newborns exhibit significant posterior frontal cortex activation to noxious stimuli.
- Cortical activation increases with postmenstrual age, indicating developmental changes.
- Decreased activation with repeated painful stimuli suggests experience-dependent neuroplasticity, possibly due to maturation and adaptation.
Abstract:
The aim of the study was to investigate whether cortical response to a repeated noxious procedure may change over time in preterm infants. Possible reasons for change are: (1) advancing maturation of central nervous system; and (2) increasing experience with noxious procedures during hospital stay. Sixteen preterm infants were recruited, with a postmenstrual age (PMA) ranging between 29 and 36 weeks. Newborns were assessed during a heel-prick procedure, once a week for at least 3 consecutive times. Multichannel near-infrared spectroscopy was used to detect cortical activation, by measuring increase in cortical oxy-haemoglobin (HbO2). Parietal, temporal, and posterior frontal areas were monitored bilaterally. By regression analysis, we studied the effect of (1) increasing PMA and (2) increasing number of heel pricks, on the magnitude of cortical activation. We observed a bilateral nociceptive event-related activation of the posterior frontal cortex, mainly contralateral to the side pricked. Additionally, we found a significant positive effect of PMA, as HbO2 progressively increased in the posterior frontal cortex (P < 0.001), bilaterally, over time. Conversely, the degree of cortical activation decreased as the number of noxious events increased (P < 0.002). We conclude the following: (1) Preterm newborns showed a significant activation of the posterior frontal cortex in association with noxious stimuli; (2) Cortical activation was progressively greater with increasing PMA; (3) There was an inverse relationship between cortical activation and the number of heel pricks. We speculate that such findings may be due to both endogenous cortical maturation and experience-dependent neuroplasticity of the developing brain (eg, synaptogenesis, synaptic pruning).
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