Kindlin-1 Regulates Astrocyte Activation and Pain Sensitivity in Rats With Neuropathic Pain
Kindlin-1 Regulates Astrocyte Activation and Pain Sensitivity in Rats With Neuropathic Pain
复制标题
Kindlin-1 调节神经性疼痛大鼠的星形胶质细胞激活和疼痛敏感性
DOI：
10.1097/aap.0000000000000780
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发表时间：
2018
影响因子：
5.1
通讯作者：
Song Xingrong
中科院分区：
文献类型：
--
作者：
Zhao Baisong;Pan Yongying;Xu Haiping;Song Xingrong
背景与目的星形胶质细胞激活参与神经病理性疼痛的发病机制，但Kindlin-1在星形胶质细胞激活和神经病理性疼痛中的作用尚未阐明。采用慢性压迫性损伤(CCI)大鼠神经病理性疼痛模型，研究Kindlin-1在神经病理性疼痛过程中的表达水平及其对疼痛敏感性的调节作用。将大鼠随机分为4组：假手术组、CCI组、CCI+kindlin-1短发夹状RNA(ShRNA)组、CCI+kindlin-1组。CCI+kindling-1shRNA组和CCI+kindlin-1组分别给予kindlin-1shRNA或kindlin-1病毒感染以降低或上调kindlin-1的表达。大鼠CCI后10d，Kindlin-1表达持续增加。结果与假手术组比较，脑挫伤后脊髓组织中胶质纤维酸性蛋白(GFAP)阳性的星形胶质细胞大量表达Kindlin-1。Kindlin-1的下调减少了GFAP在脊髓中的上调，而Kindlin-1的过度表达则促进了GFAP的表达。抑制Kindlin-1可提高CCI大鼠的机械痛阈值和热痛阈值(P<；0.05)。结论Kindlin-1可能通过影响脊髓内激活的星形胶质细胞来调节疼痛敏感性。抑制Kindlin-1可能为神经病理性疼痛的治疗提供了一个新的范例。
Background and ObjectivesAstrocyte activation has been implicated in the pathogenesis of neuropathic pain, but the involvement of kindlin-1 in astrocyte activation and neuropathic pain has not yet been illustrated. Using a chronic constriction injury (CCI) rat model of neuropathic pain, we investigated the expression levels of kindlin-1 during neuropathic pain and the influences of kindlin-1 on regulating pain sensitivity.MethodsNeuropathic pain was induced in rats by CCI of the sciatic nerve. Rats were randomly assigned to 4 groups: sham operation, CCI, CCI + kindlin-1 short hairpin RNA (shRNA), and CCI + kindlin-1 groups. Animals in the CCI + kindling-1 shRNA and CCI + kindlin-1 groups were given kindlin-1 shRNA or kindlin-1 virus infection to reduce or overexpress kindlin-1, respectively. Kindlin-1 expression was persistently increased in rats 10 days after CCI. A large proportion of glial fibrillary acidic protein (GFAP)–positive astrocytes expressed kindlin-1 in spinal cord tissues of rats after CCI.ResultsCompared with the sham operation group, CCI animals exhibited increased GFAP expression and GFAP-positive astrocytes in the spinal cord. Down-regulation of kindlin-1 reduced the up-regulation of GFAP in the spinal cord, whereas overexpression of kindlin-1 promoted elevation of GFAP levels. Kindlin-1 silencing elevated the mechanical and thermal pain thresholds of CCI rats (P< 0.05). However, overexpression of kindlin-1 aggravated CCI-induced pain sensitivity.ConclusionsKindlin-1 may regulate pain sensitivity by affecting activated astrocytes in the spinal cord. Inhibition of kindlin-1 may provide a novel paradigm for the management of neuropathic pain.