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M'Dahoma S.,French Institute of Health and Medical Research | M'Dahoma S.,University Pierre and Marie Curie | Barthelemy S.,French Institute of Health and Medical Research | Barthelemy S.,University Pierre and Marie Curie | And 15 more authors.
European Neuropsychopharmacology | Year: 2015

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. © 2015 Elsevier B.V. and ECNP. Source


Theranexus | Entity website

Theranexus Theranexus, a unique clinical stage pharmaceutical company, has developed a versatile proprietary technology leading to first in class products to address severe unmet medical needs in brain disorders. Who we are Theranexus, a unique clinical stage pharmaceutical company, has developed a versatile proprietary technology leading to first in class products to address severe unmet medical needs in brain disorders ...


Theranexus | Entity website

Luc-Andr GRANIER Chairman of the supervisory board Luc-Andr Granier, MD, PhD, founded Advicenne and has been Medical Director and Chairman of the Board since 2011. Luc-Andr Granier is an expert in the pharmaceutical development of innovative therapeutic products in the field of the central nervous system (CNS) with more than 25 years experience in the pharmaceutical (Eli Lilly and Co) and biotechnology (Synt:em, Forenap) industries ...


Theranexus | Entity website

Paris, 19th October 2015 Biotechnology company Theranexusfounded by Franck Mouthon, CEO, and Mathieu Charveriat, Scientific Directoris pleased to announce the launch of the clinical efficacy phase of its lead program, THN102, in the treatment of sleep disorders. Based on the positive results obtained in phase I, which focused on the safety of THN102, Theranexus was granted authorisation to assess the efficacy of the product ...


Theranexus | Entity website

Corporate Who we are ? Theranexus is a French biotechnology company, created in 2013. We are an operational team supported by a network of highly experienced industrial and medical leaders in our target indications ...

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