抑制小胶质细胞激活对骨癌痛小鼠疼痛维持的影响

Inhibition of microglia activation affected the maintenance of cancer pain in a murine model

目的研究鞘内注射小胶质细胞特异性抑制剂米诺环素(minocycline,MC)抑制脊髓小胶质细胞的激活对骨癌痛维持的影响。方法采用小鼠跟骨癌痛模型,♂C3H/He小鼠42只,随机分为3组(n=14),sarcoma+PBS(phosphatebuffered saline)组和sarcoma+MC组行小鼠跟骨癌痛模型制作,跟骨内注射肿瘤细胞;sham+PBS组行假手术,跟骨内注射PBS。造模后11天(post-implantation day11,PID11),每组随机取10只小鼠,sham+PBS组和sarcoma+PBS组单次鞘内注射MC溶媒(PBS 5μl),sarcoma+MC组单次鞘内注射MC(1 nmol,5μl)。各组分别在鞘内注射前、注射后0.5、1、2、4、8、24 h测定机械性痛觉超敏、冷痛觉过敏。各组剩余4只小鼠在PID12鞘内注射后1 h行非伤害性触摸右侧足底90min,分析脊髓背角c-fos蛋白的表达。结果骨癌痛导致小鼠机械性痛阈和冷痛阈降低,脊髓背角c-fos蛋白的表达上调;单次鞘内注射MC能暂时提高小鼠疼痛阈值,并抑制脊髓背角c-fos蛋白的表达。结论小胶质细胞的激活对骨癌痛的维持具有重要作用。

Aim To investigate the effect of intrathecal injection （it） of minocycline （ MC）, a selective micro- glia inhibitor, on the maintenance of pain in a murine model of cancer pain. Methods Forty-two male C3H/ He mice were randomly divided into 3 groups （n = 14 each） ： sham ＋ PBS group was operated and received 10 pd PBS injection into ealcaneus medullary space;sarco- ma ＋ PBS group and sarcoma ＋ MC group were opera- ted and received 2 × 10^5 sarcoma cells/10 μl PBS im- plantation into caleaneus medullary space. On the PID11 （post-implantation day 11 ） , 10 mice were taken from each group randomly, sarcoma ＋ PBS group and sham ＋PBS group were received 0. 9% NS （5 μl） it sarcoma ＋ MC group was received MC （1 nmol,5 μl） it Mechanical pain threshold and cold hyperalgesia as- say were measured before and after it at 0. 5,1,2,4,8,24 h. The last 4 mice of each group were received a normally non-noxious palpation of the ipsilateral heel 90 min on the PID12 after it, then the animals were killed and L4-6 segment of spinal cord was removed for analysing the c-fos expression （by immunohistochemis- try）. Results Bone cancer pain decreased the me- chanical and cold pain threshold and activated the c-los expression in the spinal cord;MC it transient attenuated bone cancer pain-induced hyperalgesia and allodynia and suppressed the expression of c-fos protein. Conclusion The activation of microglia in the spinal cord may be involved in the maintenance of bone cancer pian.