Cyclotraxin-B, a New TrkB Antagonist, and Glial Blockade by Propentofylline, Equally Prevent and Reverse Cold Allodynia Induced by BDNF or Partial Infraorbital Nerve Constriction in Mice
Cyclotraxin-B, a New TrkB Antagonist, and Glial Blockade by Propentofylline, Equally Prevent and Reverse Cold Allodynia Induced by BDNF or Partial Infraorbital Nerve Constriction in Mice
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DOI：
10.1016/j.jpain.2012.03.008
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发表时间：
2012-06-01
期刊：
影响因子：
4
通讯作者：
Pelissier, Teresa
中科院分区：
文献类型：
--
作者：
Constandil, Luis;Goich, Mariela;Pelissier, Teresa
多项证据表明，脑源性神经营养因子 (BDNF) 作为中枢疼痛感受调节剂发挥着关键作用，通过突触后 TrkB 受体发挥作用，触发细胞内信号级联反应，从而导致中枢敏化。本研究的总体目的是探讨 BDNF 在多大程度上参与三叉神经病理性疼痛的产生和维持。结果表明，在幼鼠脑池内急性注射纳克剂量的 BDNF，在触须垫皮肤上局部涂抹丙酮后，会引起持久的、剂量相关的冷异常疼痛反应。全身施用环曲素-B (CTX-B)（一种新的 TrkB 受体拮抗剂）或丙戊茶碱（一种神经胶质活化抑制剂）能够预防或逆转脑池内 BDNF 对冷伤害感受的影响。此外，CTX-B对TrkB受体的阻断抑制了在单侧眶下神经收缩后在同侧触须垫皮肤中引发或维持冷异常性疼痛的机制。这些观察结果表明，BDNF 本身能够传达由神经收缩引起的中枢敏化背后的信号传导机制的许多特征。 观点：虽然需要进一步研究来详细检查 CTX-B 强抗异常疼痛作用的机制，但该化合物可能代表了开发旨在预防和/或抑制与神经性疼痛相关的中枢敏化的新型治疗策略的有趣先导。 (C) 2012 年，美国疼痛协会
Several lines of evidence indicate that brain-derived neurotrophic factor (BDNF) plays a key role as a central pronociceptive modulator of pain, acting through postsynaptic TrkB receptors that trigger intracellular signaling cascades leading to central sensitization. The overall aim of this study was to investigate to what extent BDNF could participate in the generation and maintenance of trigeminal neuropathic pain. The results showed that acute intracisternal administration of nanogram doses of BDNF in naive mice elicited long-lasting, dose-related, cold allodynic responses to topical application of acetone onto vibrissal pad skin. The systemic administration of cyclotraxin-B (CTX-B), a new TrkB receptor antagonist, or propentofylline, an inhibitor of glial activation, was able to either prevent or reverse the effects of intracisternal BDNF on cold nociception. In addition, the blockade of TrkB receptor by CTX-B inhibited the mechanisms that either initiate or maintain cold allodynia in the ipsilateral vibrissal pad skin after unilateral constriction of the infraorbital nerve. These observations raise the possibility that BDNF is capable on its own of conveying many features of the signaling mechanisms that underlie central sensitization caused by nerve constriction.Perspective: Although further studies are necessary to examine in detail the mechanisms underlying the strong anti-allodynic action of CTX-B, this compound may represent an interesting lead for the development of novel therapeutic strategies aimed at preventing and/or suppressing central sensitization associated with neuropathic pain. (C) 2012 by the American Pain Society