title: Surgical injury in the neonatal rat alters the adult pattern of descending modulation from the rostroventral medulla.
abstract: BACKGROUND
  Neonatal pain and injury can alter long-term sensory thresholds. Descending rostroventral medulla (RVM) pathways can inhibit or facilitate spinal nociceptive processing in adulthood. As these pathways undergo significant postnatal maturation, the authors evaluated long-term effects of neonatal surgical injury on RVM descending modulation.
  
  
  METHODS
  Plantar hind paw or forepaw incisions were performed in anesthetized postnatal day (P)3 Sprague-Dawley rats. Controls received anesthesia only. Hind limb mechanical and thermal withdrawal thresholds were measured to 6 weeks of age (adult). Additional groups received pre- and post-incision sciatic nerve levobupivacaine or saline. Hind paw nociceptive reflex sensitivity was quantified in anesthetized adult rats using biceps femoris electromyography, and the effect of RVM electrical stimulation (5-200 μA) measured as percentage change from baseline.
  
  
  RESULTS
  In adult rats with previous neonatal incision (n = 9), all intensities of RVM stimulation decreased hind limb reflex sensitivity, in contrast to the typical bimodal pattern of facilitation and inhibition with increasing RVM stimulus intensity in controls (n = 5) (uninjured vs. neonatally incised, P < 0.001). Neonatal incision of the contralateral hind paw or forepaw also resulted in RVM inhibition of hind paw nociceptive reflexes at all stimulation intensities. Behavioral mechanical threshold (mean ± SEM, 28.1 ± 8 vs. 21.3 ± 1.2 g, P < 0.001) and thermal latency (7.1 ± 0.4 vs. 5.3 ± 0.3 s, P < 0.05) were increased in both hind paws after unilateral neonatal incision. Neonatal perioperative sciatic nerve blockade prevented injury-induced alterations in RVM descending control.
  
  
  CONCLUSIONS
  Neonatal surgical injury alters the postnatal development of RVM descending control, resulting in a predominance of descending inhibition and generalized reduction in baseline reflex sensitivity. Prevention by local anesthetic blockade highlights the importance of neonatal perioperative analgesia.
authors: From the UCL Institute of Child Health and Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom (S.M.W.); Department of Neuroscience, Physiology and Pharmacology, UCL, London, United Kingdom (S.M.W., M.F.); and School of Life Sciences, University of Nottingham, Nottingham, United Kingdom (G.J.H.).
authors: Suellen M
authors: SM
authors: Walker
authors: Maria
authors: M
authors: Fitzgerald
authors: Gareth J
authors: GJ
authors: Hathway
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000502:physiology; D004558:Electric Stimulation; D005260:Female; D005528:Foot / Q000294:innervation; D006930:Hyperalgesia / Q000523:psychology; D008297:Male; D008526:Medulla Oblongata / Q000254:growth & development / Q000293:injuries* / Q000601:surgery*; D009407:Nerve Block; D009475:Neurons, Afferent / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000502:physiology; D012584:Sciatic Nerve / Q000187:drug effects / Q000293:injuries; D012684:Sensory Thresholds
chemical_list: D000779:Anesthetics, Local