Encoding of mechanical nociception differs in the adult and infant brain

Abstract

Newborn human infants display robust pain behaviour and specific cortical activity following noxious skin stimulation, but it is not known whether brain processing of nociceptive information differs in infants and adults. Imaging studies have emphasised the overlap between infant and adult brain connectome architecture, but electrophysiological analysis of infant brain nociceptive networks can provide further understanding of the functional postnatal development of pain perception. Here we hypothesise that the human infant brain encodes noxious information with different neuronal patterns compared to adults. To test this we compared EEG responses to the same time-locked noxious skin lance in infants aged 0–19 days (n = 18, clinically required) and adults aged 23–48 years (n = 21). Time-frequency analysis revealed that while some features of adult nociceptive network activity are present in infants at longer latencies, including beta-gamma oscillations, infants display a distinct, long latency, noxious evoked 18-fold energy increase in the fast delta band (2–4 Hz) that is absent in adults. The differences in activity between infants and adults have a widespread topographic distribution across the brain. These data support our hypothesis and indicate important postnatal changes in the encoding of mechanical pain in the human brain.

Inferring the infant pain experience: a translational fMRI-based signature study

“…We found the NPS to be expressed similarly across infants and adults. This result aligns with a recent EEG study comparing pain responses of adults and infants 36 . Here, infants displayed noxious evoked potentials and gamma oscillations, understood in adults to be markers of primary nociceptive processing and subjective pain 47 .…”

“…In infants, noxious-evoked behaviour and brain activity have been studied and correlated 34–36 . However, determining a quantitative association between behaviour, or brain activity, and perception has remained elusive.…”

“…We see functional responses 40–43 , connectivity patterns, and resting state activity 44,45 exhibit similar features to adult brain activity. Furthermore, strong neural activity overlap between adult and infant sensory-evoked and noxious-evoked brain activity patterns have been reported across a variety of brain imaging modalities 13,36,46 .…”

The Development of Nociceptive Network Activity in the Somatosensory Cortex of Freely Moving Rat Pups

“…Scalp EEG recording in preterm human infants has demonstrated that clinically required noxious skin stimulation evokes specific nociceptive ERPs from 30 to 35 gestational weeks onwards gradually replacing the immature nonspecific burst responses (Fabrizi et al 2011). Time frequency analysis of cortical activity in full-term infants shows that nociceptive stimuli are encoded differently from that in adults (Fabrizi et al 2016) but more research is required to understand the maturation of pain representation in the human infant brain. Oscillations and their synchronization are important correlates of neuronal processing, and coordination of neural activity into whole-brain functional networks can provide valuable measures for the assessment of brain functions.…”

Neonatal repetitive pain in rats leads to impaired spatial learning and dysregulated hypothalamic-pituitary-adrenal axis function in later life

“…The current view of pain is that it arises from a distributed network of brain activity, none of which is unique to pain, but when coordinated or synchronized, results in the sensory, emotional, motivational, and cognitive experience that is pain56. Therefore, non-intervened pain, particularly that which occurs during a critical period of brain development, can cause long-term behavioral alteration in humans and animals789.…”