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Characterising the early development of human pain processing and behaviour

Presented at the Neonatal Society 2012 Autumn Meeting.

Moultrie F, Poorun R, Worley A, Adams E, Slater R

University of Oxford

Background: Newborn infants who require hospitalisation undergo many clinically-essential painful procedures during a critical period of neurodevelopment. To improve the management of pain in neonates we need to advance our understanding of the early neurodevelopmental changes that underlie the beginning of human pain processing and perception. The aim of the study was to record noxious-evoked activity in the brain and spinal cord, together with behavioural responses in order to characterise how these responses are developmentally regulated. We hypothesised that the amplitude of noxious-specific brain activity would be larger in term infants compared with preterm infants, whereas spinal reflex withdrawal activity would be larger and more sustained in preterm infants compared to term infants. Ethics approval was obtained from the National Research Ethics Service (NRES) and the Oxford University Hospitals NHS Trust.

Methods: Twenty-two infants were studied on the Newborn Intensive Care and Special Care Unit, John Radcliffe Hospital, Oxford between April and July 2012. Each infant was studied on a single occasion, when they required a clinically-essential heel lance. Electroencephalography (EEG) was used to measure nociceptivespecific brain activity, and surface electromyography (EMG) was used to measure spinal nociceptive reflex withdrawal activity. Brain activity was characterised by measurement of the amplitude of the nociceptivespecific potential. The spinal nociceptive reflex withdrawal was characterised using the root mean square (RMS) of activity post-stimulus. All infants were videoed to record evoked changes in facial expression. Basic summary statistics were analysed in Graphpad Prism.

Results: The 22 participants were clinically stable newborn infants of 29.1-40.1 weeks gestation, (gestation at birth: 24.7-39.6 weeks, postnatal age 2-68 days). One infant was excluded from EEG analysis on account of movement artefact and EMG was not successfully recorded in three infants. Nociceptive-specific brain activity was identified in 15 of 21 infants. The amplitude of the nociceptive-specific potential significantly increased with gestation at study (p=0.0157) and gestation at birth (p=0.0362) but was not dependent on postnatal age (p>0.05). EMG activity was significantly greater following noxious stimulation compared to the background EMG (n=19, p<0.001). Background EMG activity significantly increased with gestation (p=0.0378) whereas nociceptive-specific spinal reflex withdrawal activity significantly decreased with gestation (p=0.0389). When nociceptive-specific cortical activity was present there was a significant reduction in spinal reflex withdrawal activity (Mann-Witney, p<0.01). In 41% (9/22) of infants a facial response was not observed following noxious stimulation. There was no significant difference in mean EMG activity (p>0.05) or mean EEG activity (p>0.05) between facial responders and non-responders.

Conclusion: As infants mature during the neonatal period, they display progressively greater nociceptive-specific brain activity and less spinal reflex withdrawal activity. Lack of change in facial expression or minimal withdrawal of a limb in response to a painful procedure is not indicative of a decrease or absence of nociceptivespecific brain activity. Observed motor behaviour relied upon in clinical practice may therefore not reflect the degree of pain processing occurring at the level of the brain and spinal cord.

Corresponding author: f.a.moultrie@gmail.com

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