趋化因子受体CXCR3在神经病理疼痛调控中的作用以及与小胶质细胞活化的关系

Objective： CXCR3 was rarely mentioned in the mechanisms of pain modulation. Our previous study demonstrated that mRNA of CXCR3 was significantly induced in the spinal cord by peripheral formalin injury. The present study is to investigate the possible involvement of CXCR3 in neuropathic pain. Methods：Twenty adult male CXCR3 deficient mice and Thirty-five wild-type（WT）C57BL/6J mice were assigned to four groups: CXCR3-/- mice with CCI surgery(n=10); WT mice with CCI surgery(n=25); CXCR3-/- mice with sham surgery(n=10); WT mice with sham surgery(n=13); Seven mice from every group were selected randomly for the behavior test at day 0, 1, 3, 7, 14 after surgery. The rest WT CCI rats were divided randomly to five sub-groups, four of which were sacrificed and harvested the ipsilateral L4~6 spinal cords at 1 day, 3 days, 7days and 14 days. The spinal cords of three WT sham mice were also harvested at 7 days for CXCR3 western blot analysis. The sample of other mice were all sacrificed and fixed at 7 days for iba1 and p-p38 immunohistochemistry analysis. Results： (1) The protein expression of CXCR3 were upregulated in the spinal cord beginning at day 3 after CCI injury, peak at day 7 and last to the end of experiment. (2) The mechanical allodynia was delayed in the CXCR3 deficient mice which also showed a higher thermal response threshold than the WT mice. (3) There was significant attenuation of iba1 and p-p38 expression in CXCR3 deficient mice. Conclusion： We confirmed the upregulation of CXCR3 in the protein level during pain state. The absence of CXCR3 showed an improvement effect to the pain behavior and inhibits the upregulation of microglia functional marker iba1 and p-p38. It may indicate that CXCR3 is a key Chemokine receptor that involved in pain modulation, and the way it works may be via changing the function of microglia.