Wang Cunjin, Wang Hongjun, Pang Jun, Li Li, Zhang Suming, Song Ge, Li Na, Cao Junping, Zhang Licai
Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, Jiangsu, 221004, China.
J Mol Neurosci. 2014;54(2):156-63. doi: 10.1007/s12031-014-0266-y. Epub 2014 Mar 6.
Treating neuropathic pain is a major clinical challenge, and several key molecules associated with nociception have been suggested as potential targets for novel analgesics. Many studies have reported the anti-nociceptive effects of glial cell-derived neurotrophic factor (GDNF), but the underlying mechanism remains largely unknown. The present study was performed to assess the effects of GDNF in a mouse model of chronic constriction injury (CCI)-induced neuropathic pain. We also determined the potential role of E-cadherin/p120 catenin (p120ctn) signaling in these effects. Mice received an intrathecal acute injection of PBS, GDNF, and DECMA-1 (an E-cadherin functional blocking antibody) or a combination of DECMA-1 with GDNF on the testing days. Our results demonstrated that CCI caused a rapid decrease in E-cadherin and membrane-associated p120ctn in the spinal dorsal horn. Together, these data demonstrated that E-cadherin-associated p120ctn was upregulated by GDNF and that this upregulation was inhibited by pre-treatment with DECMA-1. Moreover, DECMA-1 significantly inhibited the effect of GDNF on thermal hyperalgesia. These data suggest that GDNF might have a therapeutic potential for the treatment of CCI-induced neuropathic pain and that the E-cadherin/p120ctn might play a role in GDNF-induced attenuation of thermal hyperalgesia.
治疗神经性疼痛是一项重大的临床挑战，一些与伤害感受相关的关键分子已被认为是新型镇痛药的潜在靶点。许多研究报道了胶质细胞源性神经营养因子（GDNF）的抗伤害感受作用，但其潜在机制仍 largely unknown。本研究旨在评估GDNF在慢性压迫损伤（CCI）诱导的神经性疼痛小鼠模型中的作用。我们还确定了E-钙黏蛋白/p120连环蛋白（p120ctn）信号在这些作用中的潜在作用。在测试日，小鼠接受鞘内急性注射 PBS、GDNF、DECMA-1（一种E-钙黏蛋白功能阻断抗体）或DECMA-1与GDNF的组合。我们的结果表明，CCI导致脊髓背角中E-钙黏蛋白和膜相关p120ctn迅速减少。总之，这些数据表明，GDNF上调了与E-钙黏蛋白相关的p120ctn，而这种上调被DECMA-1预处理所抑制。此外，DECMA-1显著抑制了GDNF对热痛觉过敏的作用。这些数据表明，GDNF可能对治疗CCI诱导的神经性疼痛具有治疗潜力，并且E-钙黏蛋白/p120ctn可能在GDNF诱导的热痛觉过敏减轻中发挥作用。
