目的:观察脊髓单核细胞趋化蛋白受体CCR2在大鼠骨癌痛形成过程中的可能机制。方法大鼠左侧胫骨骨髓腔内接种Walker256乳腺癌细胞制备骨癌痛模型。观察并测量各组大鼠术前1 d,术后3、6、9、10、11、12 d的机械痛阈值。术后12 d取材,免疫组织化学法检测脊髓背角星形胶质细胞标志物( GFAP)的平均光密度值( MOD),观察脊髓小胶质细胞增殖活化情况。结果与对照组相比,鞘内给予CCR2拮抗剂后大鼠机械痛阈值明显升高,脊髓GFAP表达明显降低(P<0.01)。结论鞘内注射CCR2特异性拮抗剂可能通过抑制脊髓星形胶质细胞的活化而缓解大鼠骨癌痛, CCR2可能是治疗骨癌痛新的靶点。
Aim To investigate the effect of intrathecal injection of CCR2 antagonist on pain behaviours,spinal astrocytes activation in the spinal cord in a rat model of bone cancer pain. Methods Forty female SD rats weighing 150 ~180 g were randomly divided into five groups ( n=8 each ):(Ⅰ) sham group;(Ⅱ) sham +RS102895 group;(Ⅲ) bone cancer pain group;(Ⅳ) bone cancer pain + DMSO group;(Ⅴ) bone cancer pain+RS102895 group. Rats received i. t. injections of either RS102895 (3 g·L-1 ) 10 μl or 10%DMSO 10 μl at the time of 10-12 days after the operation. Bone cancer was induced by intra-tibial inoculation of 1 × 105 Walker 256 breast cancer cell. Mechanical hind paw withdrawal threshold test was performed one day before and at 3rd,6th,9th, 10th,11th and 12th days after surgery. Immunofluorescence was used to observe the activation of the spinal astrocytes. Results Compared with group Ⅰ, the rats in bone cancer pain group appeared obvious mechanical hyperalgesia (Ⅲ、Ⅳ、Ⅴ) ,the volume,shape and mean optical den-sity ( MOD) of spinal astrocytes could be seen obvious-ly increased,groupⅡhad no obvious statistical signifi-cance (P>0. 05). Compared with group Ⅳ ,i. t. in-jections of RS102895 increased the paw mechanical withdrawal threshold, suppressed the action of astro-cytes,reduced the MOD of spinal astrocytes. Conclu-sion CCR2 might participate in the formation of bone cancer pain via activating spinal astrocytes. CCR2 will be a potential target for the treatment of bone cancer pain.