PMID- 26343858 OWN - NLM STAT- MEDLINE DCOM- 20160826 LR - 20151121 IS - 1873-7862 (Electronic) IS - 0924-977X (Linking) VI - 25 IP - 11 DP - 2015 Nov TI - Respective pharmacological features of neuropathic-like pain evoked by intrathecal BDNF versus sciatic nerve ligation in rats. PG - 2118-30 LID - S0924-977X(15)00244-8 [pii] LID - 10.1016/j.euroneuro.2015.07.026 [doi] AB - Numerous reported data support the idea that Brain Derived Neurotrophic Factor (BDNF) is critically involved in both depression and comorbid pain. The possible direct effect of BDNF on pain mechanisms was assessed here and compared with behavioral/neurobiological features of neuropathic pain caused by chronic constriction injury to the sciatic nerve (CCI-SN). Sprague-Dawley male rats were either injected intrathecally with BDNF (3.0 ng i.t.) or subjected to unilateral CCI-SN. Their respective responses to anti-hyperalgesic drugs were assessed using the Randall-Selitto test and both immunohistochemical and RT-qPCR approaches were used to investigate molecular/cellular mechanisms underlying hyperalgesia in both models. Long lasting hyperalgesia and allodynia were induced by i.t. BDNF in intact healthy rats like those found after CCI-SN. Acute treatment with the BDNF-TrkB receptor antagonist cyclotraxin B completely prevented i.t. BDNF-induced hyperalgesia and partially reversed this symptom in both BDNF-pretreated and CCI-SN lesioned rats. Acute administration of the anticonvulsant pregabalin, the NMDA receptor antagonist ketamine, the opioid analgesics morphine and tapentadol or the antidepressant agomelatine also transiently reversed hyperalgesia in both i.t. BDNF injected- and CCI-SN lesioned-rats. Marked induction of microglia activation markers (OX42, Iba1, P-p38), proinflammatory cytokine IL-6, NMDA receptor subunit NR2B and BDNF was found in spinal cord and/or dorsal root ganglia of CCI-SN rats. A long lasting spinal BDNF overexpression was also observed in BDNF i.t. rats, indicating an autocrine self-induction, with downstream long lasting TrkB-mediated neuropathic-like pain. Accordingly, TrkB blockade appeared as a relevant approach to alleviate not only i.t. BDNF- but also nerve lesion-evoked neuropathic pain. CI - Copyright (c) 2015 Elsevier B.V. and ECNP. All rights reserved. FAU - M'Dahoma, Said AU - M'Dahoma S AD - Centre de Psychiatrie et Neurosciences, INSERM UMR 894, Paris F-75014, France; Universite Pierre et Marie Curie - Paris 6, Faculte de Medecine Pierre et Marie Curie, Site Pitie-Salpetriere, Paris F-75013, France. FAU - Barthelemy, Sandrine AU - Barthelemy S AD - Centre de Psychiatrie et Neurosciences, INSERM UMR 894, Paris F-75014, France; Universite Pierre et Marie Curie - Paris 6, Faculte de Medecine Pierre et Marie Curie, Site Pitie-Salpetriere, Paris F-75013, France. FAU - Tromilin, Claire AU - Tromilin C AD - Centre de Psychiatrie et Neurosciences, INSERM UMR 894, Paris F-75014, France; Universite Pierre et Marie Curie - Paris 6, Faculte de Medecine Pierre et Marie Curie, Site Pitie-Salpetriere, Paris F-75013, France. FAU - Jeanson, Tiffany AU - Jeanson T AD - Universite Pierre et Marie Curie - Paris 6, Faculte de Medecine Pierre et Marie Curie, Site Pitie-Salpetriere, Paris F-75013, France; Theranexus, 91400 Orsay, France. FAU - Viguier, Florent AU - Viguier F AD - Centre de Psychiatrie et Neurosciences, INSERM UMR 894, Paris F-75014, France; Universite Pierre et Marie Curie - Paris 6, Faculte de Medecine Pierre et Marie Curie, Site Pitie-Salpetriere, Paris F-75013, France. FAU - Michot, Benoit AU - Michot B AD - Centre de Psychiatrie et Neurosciences, INSERM UMR 894, Paris F-75014, France; Universite Pierre et Marie Curie - Paris 6, Faculte de Medecine Pierre et Marie Curie, Site Pitie-Salpetriere, Paris F-75013, France. FAU - Pezet, Sophie AU - Pezet S AD - UMR 8249 CNRS - Brain Plasticity Unit, ESCPI-ParisTech, Paris F-75005, France. FAU - Hamon, Michel AU - Hamon M AD - Centre de Psychiatrie et Neurosciences, INSERM UMR 894, Paris F-75014, France; Universite Pierre et Marie Curie - Paris 6, Faculte de Medecine Pierre et Marie Curie, Site Pitie-Salpetriere, Paris F-75013, France; Universite Paris Descartes, Sorbonne Paris Cite - Paris 5, France. FAU - Bourgoin, Sylvie AU - Bourgoin S AD - Centre de Psychiatrie et Neurosciences, INSERM UMR 894, Paris F-75014, France; Universite Pierre et Marie Curie - Paris 6, Faculte de Medecine Pierre et Marie Curie, Site Pitie-Salpetriere, Paris F-75013, France; Universite Paris Descartes, Sorbonne Paris Cite - Paris 5, France. Electronic address: sylvie.bourgoin@upmc.fr. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150813 PL - Netherlands TA - Eur Neuropsychopharmacol JT - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology JID - 9111390 RN - 0 (Analgesics) RN - 0 (Brain-Derived Neurotrophic Factor) SB - IM MH - Analgesics/*pharmacology MH - Animals MH - Brain-Derived Neurotrophic Factor MH - *Disease Models, Animal MH - Ganglia, Spinal/drug effects/immunology/pathology MH - Hyperalgesia/drug therapy/pathology/physiopathology MH - Injections, Spinal MH - Ligation MH - Male MH - Neuralgia/*drug therapy/pathology/physiopathology MH - Neuroglia/drug effects/immunology/pathology MH - Neuroimmunomodulation/drug effects/physiology MH - Rats, Sprague-Dawley MH - Sciatic Nerve/injuries MH - Spinal Cord/drug effects/immunology/pathology MH - Touch OTO - NOTNLM OT - BDNF OT - Chronic constriction injury OT - Cyclotraxin B OT - Microglia activation OT - Neuropathic pain OT - TrkB receptor EDAT- 2015/09/08 06:00 MHDA- 2016/08/27 06:00 CRDT- 2015/09/08 06:00 PHST- 2015/04/24 00:00 [received] PHST- 2015/07/27 00:00 [revised] PHST- 2015/07/30 00:00 [accepted] PHST- 2015/09/08 06:00 [entrez] PHST- 2015/09/08 06:00 [pubmed] PHST- 2016/08/27 06:00 [medline] AID - S0924-977X(15)00244-8 [pii] AID - 10.1016/j.euroneuro.2015.07.026 [doi] PST - ppublish SO - Eur Neuropsychopharmacol. 2015 Nov;25(11):2118-30. doi: 10.1016/j.euroneuro.2015.07.026. Epub 2015 Aug 13.