Neonatal Plasticity of the Nociceptive System: Mechanisms, Effects, and Treatment of Repetitive Painful Procedures During NICU Admittance

Curr Pharm Des. 2017;23(38):5902-5910. doi: 10.2174/1381612823666170921130320.

Abstract

Introduction: In the Neonatal Intensive Care Unit (NICU), prematurely born infants undergo a range of skin breaking and painful procedures. At the same time, the spinal nociceptive system is in a sensitive developmental stage. Both neonatal repetitive painful procedures and their treatment can induce plasticity of the neonatal spinal nociceptive system, causing long-lasting alterations to pain processing and pain reactivity.

Methods: This review focuses on developmental processes related to the nociceptive network in the spinal dorsal horn and more specifically at mechanisms related to 1. Modulation of afferent systems; 2. The role of interneurons; 3. Descending inhibitory pathways; and 4. The central neuro-immune responses and microglial cell responses. The effects and possible mechanisms underlying the long-term effects of repetitive painful procedures on the developing nociceptive system as well as subsequent pharmacological treatment (acetaminophen, morphine) in early life are discussed.

Results: Repetitive stimulation of the nociceptive system in a rat model with use of needle pricks in the hind-paw closely mimics the clinical situation for infants in the NICU.

Conclusion: Activity dependent plasticity in early postnatal life induces long-lasting alterations that then may cause altered pain perception in adulthood. For a future choice of optimal analgesic drugs these considerations have to be taken into account beyond the classical classes of drugs used nowadays.

Keywords: NICU; Neonatal pain; analgesic drugs.; long-term effects; plasticity; repetitive pain.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / growth & development
  • Child Development / drug effects
  • Child Development / physiology*
  • Humans
  • Infant, Newborn
  • Intensive Care Units, Neonatal* / trends
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Pain / diagnosis
  • Pain / physiopathology*
  • Pain Measurement / drug effects
  • Pain Measurement / methods*
  • Pain Measurement / trends
  • Pain Threshold / drug effects
  • Pain Threshold / physiology
  • Patient Admission* / trends
  • Pyramidal Tracts / drug effects
  • Pyramidal Tracts / growth & development
  • Treatment Outcome