• Lasse Dührsen, Sinno H P Simons, Mark Dzietko, Kerstin Genz, Ivo Bendix, Vinzenz Boos, Marco Sifringer, Dick Tibboel, and Ursula Felderhoff-Mueser.
• Department of Neonatology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
• Neonatology. 2013 Jan 1; 103 (1): 35-43.

BackgroundUntreated 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.ObjectiveTo study the effects of neonatal pain and morphine treatment on the developing brain in a neonatal rat model.MethodsNewborn 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).ResultsFormalin 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.ConclusionsSevere 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.Copyright © 2012 S. Karger AG, Basel.

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