Normalizing GDNF expression in the spinal cord alleviates cutaneous hyperalgesia but not ongoing pain in a rat model of bone cancer pain
Normalizing GDNF expression in the spinal cord alleviates cutaneous hyperalgesia but not ongoing pain in a rat model of bone cancer pain
复制标题
脊髓中 GDNF 表达正常化可减轻骨癌疼痛大鼠模型中的皮肤痛觉过敏，但不能减轻持续性疼痛
DOI：
10.1002/ijc.30438
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发表时间：
2017-01-15
影响因子：
6.4
通讯作者：
Song, Zongbin
中科院分区：
文献类型：
--
作者：
Ding, Zhuofeng;Xu, Wei;Song, Zongbin
骨癌疼痛（BCP）是骨癌患者最常见的并发症。胶质细胞源性神经营养因子（GDNF）被认为与慢性疼痛有关。本研究采用步行者256大鼠乳腺癌细胞胫骨注射诱导大鼠BCP模型，观察GDNF的表达及其作用。早在注射后第5天就开始观察到显著的机械和热痛觉过敏和持续疼痛。在胫骨注射后第16天检测的GDNF蛋白表达水平在L3背根神经节（DRG）和腰髓中降低，但在其他脊髓水平或前扣带皮质中没有。GDNF家族配体的受体Ret的磷酸化也降低。此外，在脊髓中用慢病毒载体构建体使GDNF表达正常化显著降低了胫骨注射诱导的机械和热痛觉过敏、脊髓胶质细胞活化和pERK诱导，但不影响持续的疼痛。这些发现为GDNF作为骨癌疼痛状态的治疗性治疗提供了新的证据。
Bone cancer pain (BCP) is the most common complication in patients with bone cancer. Glial cell line-derived neurotrophic factor (GDNF) is believed to be involved in chronic pain conditions. In this article, the expression and roles of GDNF were studied in a rat model of BCP induced by tibia injection of Walker 256 rat mammary gland carcinoma cells. Significant mechanical and thermal hyperalgesia and ongoing pain were observed beginning as early as day 5 post injection. The expression level of GDNF protein examined on day 16 after tibia injection was decreased in the L3 dorsal root ganglion (DRG) and lumbar spinal cord, but not in other spinal levels or the anterior cingulate cortex. Phosphorylation of Ret, the receptor for GDNF family ligands, was also decreased. Furthermore, normalizing GDNF expression with lentiviral vector constructs in the spinal cord significantly reduced mechanical and thermal hyperalgesia, spinal glial activation, and pERK induction induced by tibia injection, but did not affect ongoing pain. Together these findings provide new evidence for the use of GDNF as a therapeutic treatment for bone cancer pain states.