激活的STAT3通过上调大鼠脊髓CXCL12的表达参与腰椎间盘髓核突出诱导的持续疼痛

ACTIVATED STAT3 MEDIATES THE PERSISTENT PAIN HYPERSENSITIVITY INDUCED BY LUMBAR DISC HERNIATION BY UPREGULATING CXCL12 EXPRESSION IN THE SPINAL CORD OF RATS

目的:探讨腰椎间盘突出症(lumbar disc herniation,LDH)能否通过激活转录因子STAT3上调脊髓CXCL12的表达介导持续疼痛。方法:采用SD成年雄性大鼠建立腰椎间盘髓核突出引起的持续疼痛模型。采用von Frey纤维丝检测大鼠50%机械刺激撤足阈值的变化,应用Western blot方法检测大鼠脊髓CXCL12和磷酸化STAT3(p-STAT3)的表达水平。此外,在行腰椎间盘髓核移植手术前鞘内置管,术后鞘内注射CXCL12中和性抗体或STAT3活性抑制剂S3I-201,持续注射7天后行为学测试检测大鼠50%机械刺激撤足阈值的变化。结果:从术后第7天开始到术后第28天,与假手术组相比较,LDH大鼠的机械痛阈显著下降(P<0.01),脊髓CXCL12和p-STAT3的表达显著升高(P<0.01);鞘内注射CXCL12的中和性抗体或STAT3活性抑制剂S3I-201能够显著抑制LDH手术引起的机械撤足阈值的降低(P<0.01),且鞘内注射S3I-201能够显著抑制LDH手术引起的脊髓CXCL12表达的上调(P<0.01)。结论:转录因子STAT3的激活通过上调脊髓CXCL12的表达介导腰椎间盘髓核突出引起的持续疼痛。

Objective:To explore whether the activation of STAT3 mediates the persistent pain induced by lumbar disc herniation(LDH)via upregulating CXCL12 expression.Methods:A model of persistent pain induced by nucleus pulposus herniation of lumbar intervertebral disk was established in male Sprague Dawley(SD)rats.Mechanical allodynia behavioral test was performed using von Frey filaments.The expression levels of the phosphorylated STAT3(p-STAT3)and CXCL12 in the spinal cord were tested by western blot.In addition,intrathecal tube was placed before transplantation of lumbar disc nucleus.The anti-CXCL12 naturalizing antibody or S3I-201,an inhibitor of STAT3 activity,was intrathecal injected,and the mechanical allodynia behaviors were assessed 7 days after intrathecal injection.Results:From 7 days to 28 days after surgery,compared with sham group,the mechanical withdrawal thresholds of LDH group were significantly reduced and the expression of CXCL12 and p-STAT3 in the spinal cord were significantly enhanced(P<0.01).Besides,intrathecal injection of anti-CXCL12 naturalizing antibody or S3I-201 markedly inhibited LDH-induced mechanical allodynia(P<0.01).Furthermore,S3I-201 also obviously reduced LDH-induced upregulation of CXCL12 expression(P<0.01).Conclusion:Activation of STAT3 mediates the persistent pain induced by the nucleus pulposus herniation of lumbar intervertebral disk via upregulating the expression of CXCL12 in the spinal cord of rats.