PMID- 30364099 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 9 DP - 2018 TI - Burst-Like Subcutaneous Electrical Stimulation Induces BDNF-Mediated, Cyclotraxin B-Sensitive Central Sensitization in Rat Spinal Cord. PG - 1143 LID - 10.3389/fphar.2018.01143 [doi] LID - 1143 AB - Intrathecal administration of brain derived neurotrophic factor (BDNF) induces long-term potentiation (LTP) and generates long-lasting central sensitization in spinal cord thus mimicking chronic pain, but the relevance of these observations to chronic pain mechanisms is uncertain. Since C-fiber activation by a high-frequency subcutaneous electrical stimulation (SES) protocol causes spinal release of BDNF and induces spinal cord LTP, we propose that application of such protocol would be a sufficient condition for generating long-lasting BDNF-mediated central sensitization. Results showed that application of burst-like SES to rat toes produced (i) rapid induction of hyperalgesia that lasted for more than 3 weeks, (ii) early increase of C-reflex activity followed by increased wind-up scores lasting for more than 1 week, and (iii) early increase followed by late decrease in BDNF protein levels and phosphorylated TrkB that lasted for more than 1 week. These changes were prevented by the TrkB antagonist cyclotraxin-B administered shortly before SES, while hyperalgesia was reversed by cyclotraxin-B administered 3 days after SES. Results suggest that mechanisms underlying central sensitization first involve BDNF release of probably neuronal origin, followed by brief increased expression of likely glial BDNF and pTrkB that could switch early phase sensitization into late one. FAU - Retamal, Jeffri AU - Retamal J AD - Laboratory of Neurobiology, Department of Biology, Faculty of Chemistry and Biology, University of Santiago de Chile, Santiago, Chile. AD - Center for the Development of Nanoscience and Nanotechnology (CEDENNA), Santiago, Chile. FAU - Reyes, Andrea AU - Reyes A AD - Laboratory of Neurobiology, Department of Biology, Faculty of Chemistry and Biology, University of Santiago de Chile, Santiago, Chile. FAU - Ramirez, Paulina AU - Ramirez P AD - Laboratory of Neurobiology, Department of Biology, Faculty of Chemistry and Biology, University of Santiago de Chile, Santiago, Chile. AD - Center for the Development of Nanoscience and Nanotechnology (CEDENNA), Santiago, Chile. FAU - Bravo, David AU - Bravo D AD - Laboratory of Neurobiology, Department of Biology, Faculty of Chemistry and Biology, University of Santiago de Chile, Santiago, Chile. AD - Center for the Development of Nanoscience and Nanotechnology (CEDENNA), Santiago, Chile. FAU - Hernandez, Alejandro AU - Hernandez A AD - Laboratory of Neurobiology, Department of Biology, Faculty of Chemistry and Biology, University of Santiago de Chile, Santiago, Chile. FAU - Pelissier, Teresa AU - Pelissier T AD - Program of Molecular and Clinical Pharmacology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile. FAU - Villanueva, Luis AU - Villanueva L AD - Centre de Psychiatrie et Neurosciences, INSERM UMR 894, Paris, France. FAU - Constandil, Luis AU - Constandil L AD - Laboratory of Neurobiology, Department of Biology, Faculty of Chemistry and Biology, University of Santiago de Chile, Santiago, Chile. AD - Center for the Development of Nanoscience and Nanotechnology (CEDENNA), Santiago, Chile. LA - eng PT - Journal Article DEP - 20181010 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC6191473 OTO - NOTNLM OT - C-reflex OT - brain-derived neurotrophic factor OT - cyclotraxin-B OT - hyperalgesia OT - subcutaneous electrical stimulation OT - windup EDAT- 2018/10/27 06:00 MHDA- 2018/10/27 06:01 PMCR- 2018/10/10 CRDT- 2018/10/27 06:00 PHST- 2018/06/28 00:00 [received] PHST- 2018/09/21 00:00 [accepted] PHST- 2018/10/27 06:00 [entrez] PHST- 2018/10/27 06:00 [pubmed] PHST- 2018/10/27 06:01 [medline] PHST- 2018/10/10 00:00 [pmc-release] AID - 10.3389/fphar.2018.01143 [doi] PST - epublish SO - Front Pharmacol. 2018 Oct 10;9:1143. doi: 10.3389/fphar.2018.01143. eCollection 2018.