From the Department of Anesthesiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University. Guangzhou, China.
Reg Anesth Pain Med. 2018 Jul;43(5):547-553. doi: 10.1097/AAP.0000000000000780.
Astrocyte 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.
Neuropathic 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.
Compared 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.
Kindlin-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.
星形胶质细胞的激活被认为与神经病理性疼痛的发病机制有关，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。本研究采用慢性坐骨神经缩窄损伤（CCI）大鼠模型，探讨了神经病理性疼痛过程中 kindlin-1 的表达水平及其对痛觉敏感性的影响。
CCI 大鼠模型的神经病理性疼痛诱导后，将大鼠随机分为 4 组：假手术组、CCI 组、CCI+kindlin-1 短发夹 RNA（shRNA）组和 CCI+kindlin-1 组。CCI+kindlin-1 shRNA 组和 CCI+kindlin-1 组大鼠给予 kindlin-1 shRNA 或 kindlin-1 病毒感染以降低或过表达 kindlin-1。CCI 后 10 天，大鼠 kindlin-1 表达持续增加。CCI 后大鼠脊髓组织中，大量胶质纤维酸性蛋白（GFAP）阳性星形胶质细胞表达 kindlin-1。
与假手术组相比，CCI 组大鼠脊髓中 GFAP 表达增加，GFAP 阳性星形胶质细胞增多。下调 kindlin-1 减少了脊髓中 GFAP 的上调，而过表达 kindlin-1 则促进了 GFAP 水平的升高。沉默 kindlin-1 可提高 CCI 大鼠的机械和热痛阈值（P < 0.05）。然而，过表达 kindlin-1 加重了 CCI 诱导的痛觉敏化。
kindlin-1 可能通过影响脊髓中激活的星形胶质细胞来调节痛觉敏感性。抑制 kindlin-1 可能为治疗神经病理性疼痛提供新的策略。
