title: Persistent changes in peripheral and spinal nociceptive processing after early tissue injury.
abstract: It has become clear that tissue damage during a critical period of early life can result in long-term changes in pain sensitivity, but the underlying mechanisms remain to be fully elucidated. Here we review the clinical and preclinical evidence for persistent alterations in nociceptive processing following neonatal tissue injury, which collectively point to the existence of both a widespread hypoalgesia at baseline as well as an exacerbated degree of hyperalgesia following a subsequent insult to the same somatotopic region. We also highlight recent work investigating the effects of early trauma on the organization and function of ascending pain pathways at a cellular and molecular level. These effects of neonatal injury include altered ion channel expression in both primary afferent and spinal cord neurons, shifts in the balance between synaptic excitation and inhibition within the superficial dorsal horn (SDH) network, and a 'priming' of microglial responses in the adult SDH. A better understanding of how early tissue damage influences the maturation of nociceptive circuits could yield new insight into strategies to minimize the long-term consequences of essential, but invasive, medical procedures on the developing somatosensory system.
authors.affiliation: Pain Research (Respiratory Critical Care and Anaesthesia), UCL Institute of Child Health, Department of Anaesthesia and Pain Medicine, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom; Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom.
authors.forename: Suellen M
authors.initials: SM
authors.lastname: Walker
authors.affiliation: Program in Neurosciences and Mental Health, The Hospital for Sick Children and Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Simon
authors.initials: S
authors.lastname: Beggs
authors.affiliation: Pain Research Center, Dept. of Anesthesiology, University of Cincinnati, Cincinnati, OH USA. Electronic address: mark.baccei@uc.edu.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Baccei
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D059225:Nociception; D010146:Pain / Q000503:physiopathology*; D059348:Peripheral Nerve Injuries / Q000503:physiopathology*; D010525:Peripheral Nerves / Q000503:physiopathology*; D013116:Spinal Cord / Q000503:physiopathology*
keywords: DRG; Dorsal horn; GABA; Glutamate; Glycine; Inflammation; Membrane excitability; Microglia; Neonatal; Pain; Patch clamp; Primary afferent; Spinal cord; Surgical incision; Synapse