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Bone cancer-induced hypersensitivity is not necessarily correlated with spinal microglial CX3CR1 overexpression in mice

Xin Zhao  Huizhu Liu  Benlong Liu  Hui Li  Ning Lü  Yu-Qiu Zhang  
【摘要】:Objective Bone cancer pain is one of the most severe symptoms in cancer patients. Previous studies have suggested that spinal microglia activation is necessary for the development of inflammatory and neuropathic pain. Our recent study showed that spinal microglial activation contributed to the maintenance of advanced bone cancer pain in a rat model. However, there is a large variation in spinal microglial activation in bone cancer pain due to differences in species/strains and origins of tumor cells. CX3CR1, a sole receptor of chemokine CX3 CL1 in the central nervous system, specifically expressed in spinal microglia. CX3 CL1/CX3CR1 signaling plays a crucial role in pathological pain via neuron-microglia communication. The present study explored whether microglial CX3CR1 in the spinal dorsal horn is involved in bone cancer pain in a mouse model. Methods Bone cancer pain model was established by injecting Lewis lung carcinoma cells into the tibia in mice. By means of immunohistochemistry and western blotting, the expression level of CX3CR1, fractalkine, GFAP and Iba1(marker of microglia) was detected. Results(1) Significant mechanical allodynia and thermal hyperalgesia developed in 14 d and persisted for at least 28 d in the ipsilateral hindpaw to tumorburned limb in both wide type mice and CX3CR1 knockout mice following Lewis lung carcinoma cells inoculation.(2)Spinal CX3CR1 and Iba-1(a marker of microglia) expression did not change during 7-28 days after tumor inoculation, while the expression level of GFAP gradually increased.(3)Intrathecal injection of a neutralizing antibody against CX3CR1 did not attenuate established hypersensitivity on wide type mice on day 21 post-tumor. Conclusion These results suggests that unlike in inflammatory and neuropathic pain, as well as in rat bone cancer pain, mice CX3CR1 in spinal microglia may be not involved in bone cancer pain.

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