Department of Neurosurgery, Neuroscience Center of Excellence, Health Sciences Center, Louisiana State University, 2020 Gravier Street, New Orleans, LA 70112, USA.
Spine J. 2010 Aug;10(8):715-20. doi: 10.1016/j.spinee.2010.03.029. Epub 2010 May 7.
Brain-derived neurotrophic factor (BDNF) and its cognate receptor, the tyrosine kinase B (TrkB), are normally expressed in neurons and implicated in multiple pathological conditions. Brain-derived neurotrophic factor is produced in the central nervous system microglia in response to noxious stimuli and appear to potentiate central sensitization. Resiniferatoxin (RTX) is an excitotoxic agonist of the vanilloid receptor 1 (VR1), a cation channel protein considered an integrator for nociception. Resiniferatoxin, administered into the dorsal root ganglia (DRG), selectively eliminates the VR1-positive neurons and improves tactile allodynia in a neuropathic pain rat model.
The goal of the present study was to evaluate the role of BDNF in RTX-induced neuropathic pain suppression.
The study design was a sciatic nerve injury animal model with intraganglionic RTX injection.
Resiniferatoxin was injected into the DRG of the L3-L6 spinal nerves after the rats displayed tactile allodynia and thermal hyperalgesia produced by a photochemical injury to the sciatic nerve. Behavioral testing and immunohistochemical and mRNA analysis of the DRG were performed to determine BDNF's role in pain modulation.
Brain-derived neurotrophic factor expression in the DRG of neuropathic rats was upregulated in the small- and medium-size neurons, whereas the upregulation was observed in the large-size neurons of non-neuropathic rat DRG. A high-dose RTX injection in the DRG of neuropathic rats led to elimination of both thermal hyperalgesia and tactile allodynia and also upregulated BDNF in the large-size neurons, similar to the nonallodynic rats. Tyrosine kinase B changes mirrored the BDNF ones.
Resiniferatoxin injection in the DRG of neuropathic rats upregulates BDNF expression in the same pattern as in the large-size neurons of non-neuropathic rats. Therefore, BDNF upregulation may have pain suppressive effects. These effects are likely mediated by TrkB.
脑源性神经营养因子（BDNF）及其同源受体酪氨酸激酶 B（TrkB）通常在神经元中表达，并与多种病理状况有关。脑源性神经营养因子在中枢神经系统小胶质细胞中产生，以响应有害刺激，并似乎增强中枢敏化。树脂毒素（RTX）是香草素受体 1（VR1）的兴奋毒性激动剂，VR1 是一种阳离子通道蛋白，被认为是伤害感受的整合器。RTX 注入背根神经节（DRG），可选择性消除 VR1 阳性神经元，并改善神经病理性疼痛大鼠模型中的触觉过敏。
本研究的目的是评估 BDNF 在 RTX 诱导的神经性疼痛抑制中的作用。
该研究设计为坐骨神经损伤动物模型，DRG 内注射 RTX。
在光化学损伤坐骨神经引起大鼠出现触觉过敏和热痛觉过敏后，将 RTX 注入 L3-L6 脊神经的 DRG。进行行为测试和 DRG 的免疫组织化学和 mRNA 分析，以确定 BDNF 在疼痛调节中的作用。
神经病理性大鼠 DRG 中的 BDNF 表达在中小神经元中上调，而非神经病理性大鼠 DRG 的大神经元中也观察到上调。在神经病理性大鼠的 DRG 中注射高剂量 RTX 导致热痛觉过敏和触觉过敏的消除，并上调大神经元中的 BDNF，类似于非过敏大鼠。酪氨酸激酶 B 的变化与 BDNF 相似。
RTX 注射到神经病理性大鼠的 DRG 中，以上调非神经病理性大鼠大神经元中 BDNF 的相同模式上调 BDNF 表达。因此，BDNF 的上调可能具有止痛作用。这些作用可能由 TrkB 介导。
