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Respective pharmacological features of neuropathic-like pain evoked by intrathecal BDNF versus sciatic nerve ligation in rats.
Eur Neuropsychopharmacol. 2015 Nov; 25(11):2118-30.EN

Abstract

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.

Authors+Show Affiliations

Centre de Psychiatrie et Neurosciences, INSERM UMR 894, Paris F-75014, France; Université Pierre et Marie Curie - Paris 6, Faculté de Médecine Pierre et Marie Curie, Site Pitié-Salpêtrière, Paris F-75013, France.Centre de Psychiatrie et Neurosciences, INSERM UMR 894, Paris F-75014, France; Université Pierre et Marie Curie - Paris 6, Faculté de Médecine Pierre et Marie Curie, Site Pitié-Salpêtrière, Paris F-75013, France.Centre de Psychiatrie et Neurosciences, INSERM UMR 894, Paris F-75014, France; Université Pierre et Marie Curie - Paris 6, Faculté de Médecine Pierre et Marie Curie, Site Pitié-Salpêtrière, Paris F-75013, France.Université Pierre et Marie Curie - Paris 6, Faculté de Médecine Pierre et Marie Curie, Site Pitié-Salpêtrière, Paris F-75013, France; Theranexus, 91400 Orsay, France.Centre de Psychiatrie et Neurosciences, INSERM UMR 894, Paris F-75014, France; Université Pierre et Marie Curie - Paris 6, Faculté de Médecine Pierre et Marie Curie, Site Pitié-Salpêtrière, Paris F-75013, France.Centre de Psychiatrie et Neurosciences, INSERM UMR 894, Paris F-75014, France; Université Pierre et Marie Curie - Paris 6, Faculté de Médecine Pierre et Marie Curie, Site Pitié-Salpêtrière, Paris F-75013, France.UMR 8249 CNRS - Brain Plasticity Unit, ESCPI-ParisTech, Paris F-75005, France.Centre de Psychiatrie et Neurosciences, INSERM UMR 894, Paris F-75014, France; Université Pierre et Marie Curie - Paris 6, Faculté de Médecine Pierre et Marie Curie, Site Pitié-Salpêtrière, Paris F-75013, France; Université Paris Descartes, Sorbonne Paris Cité - Paris 5, France.Centre de Psychiatrie et Neurosciences, INSERM UMR 894, Paris F-75014, France; Université Pierre et Marie Curie - Paris 6, Faculté de Médecine Pierre et Marie Curie, Site Pitié-Salpêtrière, Paris F-75013, France; Université Paris Descartes, Sorbonne Paris Cité - Paris 5, France. Electronic address: sylvie.bourgoin@upmc.fr.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26343858

Citation

M'Dahoma, Saïd, et al. "Respective Pharmacological Features of Neuropathic-like Pain Evoked By Intrathecal BDNF Versus Sciatic Nerve Ligation in Rats." European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology, vol. 25, no. 11, 2015, pp. 2118-30.
M'Dahoma S, Barthélemy S, Tromilin C, et al. Respective pharmacological features of neuropathic-like pain evoked by intrathecal BDNF versus sciatic nerve ligation in rats. Eur Neuropsychopharmacol. 2015;25(11):2118-30.
M'Dahoma, S., Barthélemy, S., Tromilin, C., Jeanson, T., Viguier, F., Michot, B., Pezet, S., Hamon, M., & Bourgoin, S. (2015). Respective pharmacological features of neuropathic-like pain evoked by intrathecal BDNF versus sciatic nerve ligation in rats. European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology, 25(11), 2118-30. https://doi.org/10.1016/j.euroneuro.2015.07.026
M'Dahoma S, et al. Respective Pharmacological Features of Neuropathic-like Pain Evoked By Intrathecal BDNF Versus Sciatic Nerve Ligation in Rats. Eur Neuropsychopharmacol. 2015;25(11):2118-30. PubMed PMID: 26343858.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Respective pharmacological features of neuropathic-like pain evoked by intrathecal BDNF versus sciatic nerve ligation in rats. AU - M'Dahoma,Saïd, AU - Barthélemy,Sandrine, AU - Tromilin,Claire, AU - Jeanson,Tiffany, AU - Viguier,Florent, AU - Michot,Benoit, AU - Pezet,Sophie, AU - Hamon,Michel, AU - Bourgoin,Sylvie, Y1 - 2015/08/13/ PY - 2015/04/24/received PY - 2015/07/27/revised PY - 2015/07/30/accepted PY - 2015/9/8/entrez PY - 2015/9/8/pubmed PY - 2016/8/27/medline KW - BDNF KW - Chronic constriction injury KW - Cyclotraxin B KW - Microglia activation KW - Neuropathic pain KW - TrkB receptor SP - 2118 EP - 30 JF - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology JO - Eur Neuropsychopharmacol VL - 25 IS - 11 N2 - 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. SN - 1873-7862 UR - https://www.unboundmedicine.com/medline/citation/26343858/Respective_pharmacological_features_of_neuropathic_like_pain_evoked_by_intrathecal_BDNF_versus_sciatic_nerve_ligation_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0924-977X(15)00244-8 DB - PRIME DP - Unbound Medicine ER -