title: Effects of repetitive exposure to pain and morphine treatment on the neonatal rat brain.
abstract: BACKGROUND
  Untreated exposure to pain in preterm neonates might damage the vulnerable premature brain and alter development. Pain treatment is limited because analgesic agents may also have adverse neurodevelopmental consequences in newborns.
  
  
  OBJECTIVE
  To study the effects of neonatal pain and morphine treatment on the developing brain in a neonatal rat model.
  
  
  METHODS
  Newborn rats were randomly assigned to: treatment with formalin injections (group 1), saline injections (group 2) and controls receiving no injections (group 3). Treatment was given on postnatal days 1-3 (model A), 1-5 (model B) and 10-12 (model C). Brains were studied histologically and protein expression was evaluated (protein kinase C epsilon and doublecortin). Effects of preemptive morphine treatment were studied in the same models (models A+M and B+M).
  
  
  RESULTS
  Formalin injections resulted in increased apoptotic scores in models A and B. Saline injections increased the number of degenerative cells only in model B. Morphine showed protective effects in formalin-treated animals of model A+M and saline-treated animals of model B+M only. In model C, no neurodegenerative effects were detected. The protein expression of doublecortin showed a pain-related upregulation in the thalamus region, whereas protein kinase C epsilon expression was upregulated in the cortex.
  
  
  CONCLUSIONS
  Severe inflammatory pain and pain caused by repetitive injections in neonatal rats may cause major changes in the developing brain during the first week of life. Morphine may only protect the newborn brain against these changes in specific situations.
authors.affiliation: Department of Neonatology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Lasse
authors.initials: L
authors.lastname: Dührsen
authors.forename: Sinno H P
authors.initials: SH
authors.lastname: Simons
authors.forename: Mark
authors.initials: M
authors.lastname: Dzietko
authors.forename: Kerstin
authors.initials: K
authors.lastname: Genz
authors.forename: Ivo
authors.initials: I
authors.lastname: Bendix
authors.forename: Vinzenz
authors.initials: V
authors.lastname: Boos
authors.forename: Marco
authors.initials: M
authors.lastname: Sifringer
authors.forename: Dick
authors.initials: D
authors.lastname: Tibboel
authors.forename: Ursula
authors.initials: U
authors.lastname: Felderhoff-Mueser
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000503:physiopathology; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D005557:Formaldehyde; D009020:Morphine / Q000009:adverse effects / Q000627:therapeutic use*; D009294:Narcotics / Q000009:adverse effects / Q000627:therapeutic use; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology; D010146:Pain / Q000139:chemically induced / Q000151:congenital / Q000188:drug therapy* / Q000503:physiopathology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012008:Recurrence
chemical_list: C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D009294:Narcotics; D005557:Formaldehyde; D009020:Morphine