title: Nociceptive behavior following hindpaw burn injury in young rats: response to systemic morphine.
abstract: OBJECTIVE
  Develop a burn injury model in young age rats.
  
  
  BACKGROUND
  Management of pain after burn injury in pediatric patients is an unresolved clinical issue.
  
  
  METHODS
  A burn injury model in young rats of 3-4 weeks old was developed by briefly immersing the dorsal part of the right hindpaw in a hot water bath (85°C) for 12 seconds under pentobarbital anesthesia.
  
  
  RESULTS
  Burn injury, but not sham control, induced nociceptive behaviors (mechanical allodynia, thermal hyperalgesia) when examined on post-injury day 2, 4, and 7. In burn-injured rats, there was the upregulated expression of the NR1 subunit of the N-methyl-d-aspartate (NMDA) receptor, Akt1, Akt2, and protein kinase C γ (PKCγ), but downregulated expression of neuronal nitric oxide synthase (NOS), inducible NOS, and glycogen synthase kinase-3β, within the spinal cord dorsal horn ipsilateral to burn injury. Moreover, intraperitoneal administration of a clinically available NMDA receptor antagonist dextromethorphan (30 mg/kg, once daily × 7 days beginning on day 7 after burn injury) attenuated mechanical allodynia and thermal hyperalgesia in burn-injured rats. Different from our previous finding in adult burn-injured rats; however, burn injury in young rats of this age did not spontaneously shift the morphine antinociceptive response curve to the right within the dose range used in the study when exposed to morphine for the first time, suggesting that the development of intrinsic tolerance to morphine antinociception may be different from adult rats following burn injury.
  
  
  CONCLUSIONS
  Our data suggest that this model may be used to explore the mechanisms of burn injury-induced nociception in young rats and to differentiate the sequelae from burn injury between adult and young rats under certain experimental conditions.
authors.affiliation: MGH Center for Translational Pain Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Shuxing
authors.initials: S
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Ma
authors.forename: Lucy
authors.initials: L
authors.lastname: Chen
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Tian
authors.forename: Jianren
authors.initials: J
authors.lastname: Mao
authors.forename: Jeevendra J A
authors.initials: JJ
authors.lastname: Martyn
mesh_terms: D000375:Aging / Q000502:physiology; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D002056:Burns / Q000150:complications / Q000473:pathology / Q000523:psychology*; D003915:Dextromethorphan / Q000008:administration & dosage / Q000627:therapeutic use; D038362:Glycogen Synthase Kinase 3 / Q000096:biosynthesis; D000071679:Glycogen Synthase Kinase 3 beta; D006614:Hindlimb / Q000293:injuries*; D006930:Hyperalgesia / Q000188:drug therapy / Q000523:psychology; D007150:Immunohistochemistry; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000627:therapeutic use*; D052247:Nitric Oxide Synthase Type II / Q000502:physiology; D010146:Pain / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology*; D010147:Pain Measurement / Q000187:drug effects; D020671:Posterior Horn Cells / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013116:Spinal Cord / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D016194:Receptors, N-Methyl-D-Aspartate; D003915:Dextromethorphan; D009020:Morphine; D052247:Nitric Oxide Synthase Type II; C494920:Akt1 protein, rat; C494923:Akt2 protein, rat; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3