Cerebral processing of pain in school-aged children with neonatal nociceptive input: An exploratory fMRI study

Abstract

Due to maturation-related plasticity of the developing nociceptive system, neonatal nociceptive input, as induced by medical procedures in the neonatal intensive care unit (NICU), may cause long-term alterations in pain processing. Using functional magnetic resonance imaging, this study investigated the cerebral pain response in school-aged children and adolescents (11-16 yr) with experience in a NICU after preterm (<or=31 weeks gestational age, N=9) or fullterm birth (>or=37 weeks gestational age, N=9) as compared to fullterm control children without early hospitalization (N=9). NICU children had been recruited retrospectively among former patients of the Children's University Hospital Mannheim. All children had participated in our previous studies [46,49] entailing psychophysical measurements. In response to tonic (30s) heat stimuli of individually adjusted moderate pain intensity, which were of comparable temperature across groups, the preterm but not the fullterm NICU children exhibited significant activations in a number of brain regions (thalamus, anterior cingulate cortex, cerebellum, basal ganglia, and periaquaeductal gray) that were not significantly activated in controls. The preterms showed significantly higher activations than controls in primary somatosensory cortex, anterior cingulate cortex, and insula. This exaggerated brain response was pain-specific and was not observed during non-painful warmth stimulation. Preterms' continuous pain ratings revealed a tendency for increased sensitization within and a lack of habituation across trials. In highly vulnerable children such as preterms, neonatal nociceptive input may, aside from other neurodevelopmental consequences, persistently increase the gain within pain pathways.

Sex-related long-term behavioral and hippocampal cellular alterations after nociceptive stimulation throughout postnatal development in rats

“…Recent clinical follow up studies have demonstrated that in adulthood, former preterm children display altered pain threshold (Hermann et al, 2006;Hohmeister et al, 2010;Walker et al, 2009) and decreased modulatory pain mechanisms (Goffaux et al, 2008). Ten year-old former preterm infants rate medical-related pain pictures as more intense that other pain pictures, indicating that they may have more pain memories than age-matched full term infants (Grunau et al, 1998).…”

A systematic review of the effects of repeated painful procedures in infants: Is there a potential to mitigate future pain responsivity?

“…When exposed to tonic heat, preterm children exhibited significant activation in brain regions not activated in controls. Moreover, those preterm infants that received analgesia exhibited a markedly smaller loss of brain matter than controls [28] .…”

“…Two retrospective cohort studies found that both preterm and term children with NICU experience displayed greater sensitization to tonic heat [23,28] . When exposed to tonic heat, preterm children exhibited significant activation in brain regions not activated in controls.…”

“…Moreover, there is an association between greater neonatal procedural pain and supraspinal alterations. In preterm infants there are increased fluctuations in intracranial pressure leading to early intraventricular hemorrhage [12] , heightened plasticity of the neonatal brain [12] , significant activation of brain regions not activated by controls [28] , and a reduced white and subcortical gray matter [29] .…”

Translational studies identify long-term impact of prior neonatal pain experience

“…2B) [79; 82] and produced a different fMRI pattern of cerebral activation in preterm children 9-14 years post NICU. [83] In addition, fewer EP adolescents tolerated a cold pressor test, with earlier withdrawal of the hand from an ice water bath (Fig. 2C) [198].…”