Sun Shan, Cao Hong, Han Mei, Li Ting-Ting, Pan Hai-Li, Zhao Zhi-Qi, Zhang Yu-Qiu
Institutes of Brain Science, Institute of Neurobiology, Fudan University, 138 Yixueyuan, Shanghai 200032, China.
Pain. 2007 May;129(1-2):64-75. doi: 10.1016/j.pain.2006.09.035. Epub 2006 Nov 22.
Fractalkine, a chemokine binding to only one known receptor CX3CR1, has recently been proposed to be a neuron-to-glia signal in the spinal cord leading to microglial activation and glially dependent pain facilitation. The previous studies explored that blockade of endogenous fractalkine, using anti-CX3CR1 neutralizing antibody, dose-dependently attenuated neuropathic pain. The present study examined the role of endogenous fractalkine in inflammatory pain. Intra-articular injection of complete Freund's adjuvant (CFA)-induced rat ankle joint monoarthritis (MA) model was used. Western blot analysis revealed that CX3CR1 expression in the spinal cord was significantly increased following CFA-induced MA. Intrathecal injection of anti-CX3CR1 neutralizing antibody both delayed the development of mechanical allodynia and thermal hyperalgesia, and reversed established pain facilitation. Furthermore, blockade of CX3CR1 significantly suppressed activation of spinal glia, especially microglia, evoked by MA. These data provided new evidence for the contribution of endogenous fractalkine to the initiation and early maintenance of inflammatory pain facilitation via activating spinal microglia.
趋化因子，一种仅与一种已知受体CX3CR1结合的趋化因子，最近被认为是脊髓中从神经元到神经胶质细胞的信号，可导致小胶质细胞活化和神经胶质细胞依赖性疼痛易化。先前的研究发现，使用抗CX3CR1中和抗体阻断内源性趋化因子，可剂量依赖性地减轻神经性疼痛。本研究检测了内源性趋化因子在炎性疼痛中的作用。采用关节内注射完全弗氏佐剂（CFA）诱导的大鼠踝关节单关节炎（MA）模型。蛋白质免疫印迹分析显示，CFA诱导MA后，脊髓中CX3CR1的表达显著增加。鞘内注射抗CX3CR1中和抗体既延迟了机械性异常性疼痛和热痛觉过敏的发展，又逆转了已确立的疼痛易化。此外，阻断CX3CR1可显著抑制MA诱发的脊髓神经胶质细胞，尤其是小胶质细胞的活化。这些数据为内源性趋化因子通过激活脊髓小胶质细胞对炎性疼痛易化的起始和早期维持作用提供了新证据。
