Pain activates cortical areas in the preterm newborn brain

Abstract

To study the patterns of supraspinal pain processing in neonates, we hypothesized that acute pain causes haemodynamic changes associated with activation of the primary somatosensory cortex. Forty preterm neonates at 28-36 weeks of gestation (mean=32.0) and at 25-42 h (mean=30.7) of age were studied following standardized tactile (skin disinfection) and painful (venipuncture) stimuli. Changes in regional cerebral haemodynamics were monitored by near infrared spectroscopy (NIRS) over both somatosensory cortices in 29 newborns, and over the contralateral somatosensory and occipital areas in 11 newborns. Heart rate (HR) and peripheral oxygen saturation (SaO2) were recorded simultaneously with NIRS parameters: oxygenated [HbO2], deoxygenated, and total hemoglobin. Tactile stimulation produced no changes in HR or SaO2. HR increased in the first 20s (p<0.001), while SaO2 decreased during the 40s after venipuncture (p<0.0001). Following tactile or painful stimulation, [HbO2] increased bilaterally regardless of which hand was stimulated (p<0.0001). Pain-induced [HbO2] increases in the contralateral somatosensory cortex (p<0.05) were not mirrored in the occipital cortex (p>0.1). Pain-related [HbO2] increases were more pronounced in male neonates (p<0.05 on left, p<0.001 on right), inversely correlated with gestational age (r=-0.53 on left, p<0.01; r=-0.42 on right, p<0.05) and directly correlated with postnatal age (r=0.75 on left, p<0.0001; r=0.67 on right, p<0.0001). Painful and tactile stimuli elicit specific haemodynamic responses in the somatosensory cortex, implying conscious sensory perception in preterm neonates. Somatosensory cortical activation occurs bilaterally following unilateral stimulation and these changes are more pronounced in male neonates or preterm neonates at lower gestational ages.

Electroencephalographic Response to Procedural Pain in Healthy Term Newborn Infants

“…Comparable to the results in the present study, awake subjects reacted more to the stimulus (29). Together with the findings by Fernandez et al, these studies suggest the presence of a transient and delayed (Ͼ10 s) electrographic (EEG) or hemodynamic (NIRS) response to pain stimuli (10,28,29).…”

“…Such EEG activation might be of long latency and long lasting and could be associated with changes in cerebral blood flow. Hemodynamic responses to pain were evaluated by near infrared spectroscopy (NIRS) in newborn infants, an increase in oxygenated Hb was found over the central cortical regions (28,29). Comparable to the results in the present study, awake subjects reacted more to the stimulus (29).…”

The Emergence of Human Consciousness: From Fetal to Neonatal Life

“…Interestingly, the cortical responses to noxious stimulation were found to be greater in awake than in sleeping infants (39). Moreover, the bilateral activation noticed in the Bartocci et al (40) study was suggested to include the S 2 cortex, anterior insula, ventral premotor area, and anterior cingulate cortex which belong to the GNW circuits.…”

Ketamine Reduces the Cell Death Following Inflammatory Pain in Newborn Rat Brain

“…Exposure to repetitive or prolonged pain occurs during critical periods of brain development in preterm neonates (8,22), which may alter the structure and function of their developing brains (23,24). Brief inflammatory pain in the right forepaw led to bilateral increases in neuronal activation, with a shift from subcortical to cortical processing between P7 and P14, and to increased cell death occurring more prominently at P1 and P7 than at P14.…”