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.