TNF-α在骨质疏松性疼痛中的作用

Effect of TNF-α on osteoporosis pain

目的:探讨肿瘤坏死因子α(TNF-α)在骨质疏松性疼痛中的作用。方法:40只5月龄Sparague-Dawley(SD)雌性大鼠随机分为假手术组(sham组,16只)和去卵巢组(Ovx组,24只)。Ovx术后第5周开始应用上下法(up-down method)和撤尾法(tail withdrawtest)对2组大鼠进行疼痛行为测量,每周1次。术后第8周每组分别杀死8只大鼠,取腰5背根神经节,用免疫荧光方法检测腰5背根神经节中TNF-α的表达。Ovx组剩余的16只大鼠再随机分成Ovx-1组和Ovx-2组,其中Ovx-2组予腹腔注射TNF-α合成抑制剂沙利度胺(50mg/kg,每天1次);Ovx-1组和sham组则分别注射等量的生理盐水。继续应用上下法和撤尾法对sham、Ovx-1、Ovx-2组进行疼痛行为测量至术后10周结束。结果:(1)术后第5、6、7、8周,Ovx组机械刺激疼痛阈值及热刺激的撤尾潜伏期均显著低于sham组(P<0.01);术后第9、10周,注射沙利度胺的Ovx-2组其机械刺激疼痛阈值和热刺激的撤尾潜伏期与sham组无显著差别(P>0.05),而显著高于Ovx-1组(P<0.05)。(2)Ovx组腰5背根神经节中TNF-α的表达显著高于sham组,差别显著(P<0.01)。结论:TNF-α可能在绝经后骨质疏松性疼痛中发挥重要作用,并可能通过作用于背根神经节引起痛觉敏感,抑制TNF-α的合成可缓解绝经后骨质疏松性疼痛。

AIM:To study the effect of TNF-α on osteoporosis pain.METHODS:Forty female Sparague-Dawley rats,5 months old,were either sham-operated(sham)or ovariectomized(Ovx),and assigned to sham group(n=16)and Ovx group(n=24).Pain behavioral tests with up-down method and tail withdrawal test were performed once a week beginning at 5th week after the operation.At 8th week after the operation,8 rats in each group were sacrificed and the L5 dorsal root ganglions(DRG)were collected.The expression of TNF-α in L5 DRG was measured by immunofluorescence.The remaining rats in Ovx group were assigned to 2 subgroups:Ovx-1 and Ovx-2.The rats in Ovx-2 group were administered with thalidomide(an inhibitor of TNF-α synthesis,50 mg/kg)once a day,while the animals in Ovx-1 group were given same volume of saline.Pain behavioral tests continued to be performed once a week until 10th week after operation.RESULTS:(1)The results of pain behavioral tests showed that the mechanical paw withdrawal threshold and heat tail withdrawal latency in Ovx group at 5th,6th,7th and 8th week after surgery were significantly lower than those in sham group(P<0.01).After administration with thalidomide,the mechanical paw withdrawal threshold and heat tail withdrawal latency in Ovx-2 group were restored to the level of sham group,and significantly higher than those in Ovx-1 group(P<0.05).(2)The expression of TNF-α in L5 DRG was significantly higher in Ovx group than that in sham group(P<0.01).CONCLUSION:TNF-α may play an important role in osteoporosis pain by inducing hyperalgesia through taking action on DRG.Inhibition of TNF-α synthesis may relieve menopause osteoporosis pain.