Ror2 mediates chronic post-thoracotomy pain by inducing the transformation of A1/A2 reactive astrocytes in rats

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.