Early Pain, Beware the Brain! Long-term effects of neonatal pain experiences

The past twenty years have seen great progress in our knowledge of paediatric pain. Especially our understanding of neonatal pain processing and neurobehavioral development has much deepened. Today, the human central nervous system (CNS) is generally acknowledged to be very immature at birth and to show great plasticity during the first year of life. Andrews and Fitzgerald most clearly demonstrated the immaturity of the CNS in humans, in that pain on the short-term decreased the pain threshold. However, until now only few studies have evaluated the prolonged effects of neonatal pain exposure in humans, and results are conflicting. . In order to evaluate whether pain or tissue damage in early life will lead to hypersensitivity persisting into childhood, we performed a cross-sectional study (Chapter 2). A total of 164 infants were included to determine if major surgery within the first 3 months of life increases pain sensitivity during subsequent surgery. Moreover, we wanted to evaluate whether apart from subsequent surgery in the same dermatome, also subsequent surgery in a different dermatome would alter pain sensitivity. All children received standard intraoperative and postoperative pain management. Rescue analgesic administration was guided by a treatment algorithm. Outcome measures to determine differences in pain sensitivity were assessed by the intraoperative fentanyl intake and by (nor)epinephrine plasma concentrations. Observational pain ratings from the COMFORT behaviour scale and Visual Analogue Scale (VAS), morphine intake and (nor)epinephrine plasma concentrations, served to assess differences in postoperative pain sensitivity. We found that only the infants previously operated upon in the same dermatome needed more intraoperative fentanyl, had higher COMFORT and VAS scores, had greater (nor)epinephrine plasma concentrations, and also needed more morphine than did infants with no prior surgery. The children previous operated upon in another dermatome only demonstrated higher postoperative analgesic requirements and norepinephrine plasma concentrations in comparison with infants with no prior surgery. These preliminary findings could indicate that neuroanatomical changes in the spinal and possibly also supraspinal nervous system have developed as a result of neonatal surgery. We conclude that the long-term consequences of surgery in early infancy are greatest in areas of prior tissue damage, which may portend limited clinical but important neurobiological differences.

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