Ror2 mediates chronic post-thoracotomy pain by inducing the transformation of A1/A2 reactive astrocytes in rats
Ror2 mediates chronic post-thoracotomy pain by inducing the transformation of A1/A2 reactive astrocytes in rats
复制标题
Ror2通过诱导大鼠A1/A2反应性星形胶质细胞的转化介导慢性开胸术后疼痛
DOI：
10.1016/j.cellsig.2021.110183
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发表时间：
2021-11-02
影响因子：
4.8
通讯作者：
Huang, Yuguang
中科院分区：
文献类型：
--
作者：
Liu, Chaoqun;Shen, Le;Huang, Yuguang
Ror 2在神经元发育、神经元可塑性和神经病理性疼痛中起重要作用。在我们之前的初步研究中，我们发现，Ror 2和GFAP（星形胶质细胞的标志物）的蛋白水平增加，在胸背根神经节术后第7天（POD）POD 21与慢性开胸术后疼痛（CPTP）的大鼠。在本研究中，我们的目的是进一步探讨Ror 2和活化的星形胶质细胞在CPTP发展过程中的作用。CPTP组大鼠脊髓背角Ror 2、c-JUN和C3 aR水平升高，活化的星形胶质细胞主要以A1表型表达。在CPTP大鼠中，敲低Ror 2可减轻开胸引起的机械性痛觉过敏和冷异常性疼痛，并逆转反应性星形胶质细胞的A1/A2比值，下调c-JUN和C3 aR的表达。这些结果表明，Ror 2通过调节CPTP中c-JUN和C3 aR的表达，介导了A1/A2反应性星形胶质细胞的转化。此外，抑制Ror 2可用作帮助预防CPTP的新策略。
Ror2 plays an important role in neuronal development, neuronal plasticity, and neuropathic pain. In our previous pilot study, we found that Ror2 and GFAP (a marker of astrocytes) protein levels increased in thoracic dorsal root ganglia from postoperative day (POD) 7 to POD 21 in rats with chronic post-thoracotomy pain (CPTP). In the present study, we aimed to further explore the roles of Ror2 and activated astrocytes during CPTP development. Ror2, c-JUN, and C3aR levels increased and the activated astrocytes were mainly expressed as the A1 phenotype in the spinal cord dorsal horn of the rats with CPTP. The knockdown of Ror2 in the spinal cord astrocytes alleviated thoracotomy-induced mechanical hyperalgesia and cold allodynia as well as reverted the A1/A2 ratio of the reactive astrocytes, downregulating the expression of c-JUN and C3aR in rats with CPTP. These results suggest that Ror2 in the spinal cord astrocytes mediates the transformation of A1/A2 reactive astrocytes via regulating the expressions of the c-JUN and C3aR in CPTP. Furthermore, the suppression of Ror2 could be utilized as a new strategy to help prevent CPTP.