Respective pharmacological features of neuropathic-like pain evoked by intrathecal BDNF versus sciatic nerve ligation in rats

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• 作者：Saï ; d M&rsquo ; Dahoma^a ; ^b ; Sandrine Barthé ; lemy^a ; ^b ; Claire Tromilin^a ; ^b ; Tiffany Jeanson^b ; ^d ; Florent Viguier^a ; ^b ; Benoit Michot^a ; ^b ; Sophie Pezet^e ; Michel Hamon^a ; ^b ; ^c ; Sylvie Bourgoin^a ; ^b ; ^c ; ^{sylvie.bourgoin@upmc.fr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：BDNF ; Neuropathic pain ; Chronic constriction injury ; Microglia activation ; TrkB receptor ; Cyclotraxin B
• 刊名：European Neuropsychopharmacology
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：25
• 期：11
• 页码：2118-2130
• 全文大小：3333 K

文摘

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.