BoNT/A和倍他米松对骨关节炎模型大鼠镇痛效果比较

COMPARISON OF THE ANALGESIC EFFECTS BETWEEN BOTULINUM TOXIN A AND BETAMETHASONE IN RATS WITH OSTEOARTHRITIS

目的 比较关节腔内注射A型肉毒毒素(BoNT/A)和倍他米松对单碘乙酸钠(MIA)诱导的大鼠骨关节炎疼痛的作用。方法 向大鼠踝关节腔内注射MIA诱导骨关节炎模型,将造模成功的大鼠随机分为生理盐水组、倍他米松组、BoNT/A组,每组15只,分别向关节腔内注入生理盐水25μL、复方倍他米松25μL、BoNT/A 25μL(5 U),并于给药后0、1、3、7、14、21 d评估大鼠患肢机械性刺激撤足阈值(PWT)及负重情况;应用蛋白印迹法检测给药7、14、21 d后大鼠脊髓背角内P2X4R的表达情况。结果 倍他米松组大鼠给药后3、7 d的PWT值较生理盐水组改善明显(F=2.74、3.14,P<0.05),给药后各时间点大鼠后肢支撑力百分比与生理盐水组相比差异均无统计学意义(P>0.05);BoNT/A组大鼠给药后14、21 d的PWT值较生理盐水组改善明显(F=11.90、13.25,P<0.01),后肢支撑力百分比在给药7、14、21 d改善明显(F=2.80~127.02,P<0.05)。BoNT/A能抑制脊髓背角内P2X4R的表达(F=43.04~150.36,P<0.05),而倍他米松对其无影响。结论 与倍他米松相比,BoNT/A治疗骨关节炎疼痛起效时间慢,但其镇痛作用持续时间更长,镇痛效果更明显。

Objective To compare the analgesic effects of intra-articular injection of botulinum toxin A(BoNT/A) and betamethasone on rats with osteoarthritis pain induced by sodium monosodium iodoacetate(MIA). Methods The rats received intra-articular injection of MIA to their ankles to induce an osteoarthritis model. The model rats were randomly divided into normal saline group(n=15), betamethasone group(n=15), and BoNT/A group(n=15), which received intra-articular injection of 25 μL of normal saline, 25 μL of compound betamethasone, and 25 μL(5 U) of BoNT/A, respectively. The mechanical paw withdrawal threshold and weight bearing of the affected limb were evaluated on the 0, 1 st, 3 rd, 7 th, 14 th, and 21 st day after administration. Western blot was used to determine the expression of P2 X4 R in the spinal dorsal horn of rats on 7,14, and 21 d after administration. Results On days 3 and 7 after administration, the rats in the betamethasone group had significantly improved mechanical paw withdrawal threshold compared with those in the normal saline group(F=2.74,3.14;P<0.01). At each time point after administration, there was no significant difference in the percentage weight-bearing of the affected limb between the rats in the betamethasone group and the normal saline group(P>0.05). The rats in the BoNT/A group had significantly improved mechanical paw withdrawal threshold compared with those in the normal saline group on days 14 and 21 after administration(F=11.90,13.25;P<0.01) and significantly improved percentage weight-bearing of the affected limb on days 7,14, and 21 after administration(F=2.80-127.02,P<0.05). BoNT/A inhibited the expression of P2 X4 R in the spinal dorsal horn(F=43.04-150.36,P<0.05), while betamethasone had no effect on it. Conclusion Compared with betamethasone, BoNT/A has a slower onset time in the treatment of osteoarthritis pain, but it exhibits a longer and better analgesic effect.