Molecular Mechanisms Underlying The Effect Of Intrathecal LV-SOCS3 Injection On Pain Behaviors In A Rat Model Of Bone Cancer

Objective:To investigate the effects of suppressor of cytokine signaling 3(SOCS3)overexpression by intrathecal injection lentiviral(LV)-SOCS3 on the pain behaviors and mechanism research in a rat model of bone cancer pain induced by breast cancer cells.Methods:Rats were injected with breast cancer cells to establish the models of bone cancer pain and control rats were injected with equal volume of normal saline(NS).Six model rats were treated by intrathecal LV-SOCS3 injection,and the other six rats were treated by intrathecal injection of LV-NC after one week of cancer cells injection.The paw withdrawal latency(PWL)to thermal stimulation and paw withdrawal threshold(PWT)to von Frey filament stimulation were carried out on control group,bone cancer group,LV-SOCS3 group and LV-NC group.Western blotting was performed to detect changes of SOCS3,NF-?B and P2X3 receptors(P2X3R)at protein levels in L2-L5 dorsal root ganglion(DRGs)in different groups.Results:All rats presented evident mechanical and thermal hyperalgesia after intra-tibial injection of breast cancer cells,whose PWT and PWL were lower than those of control group.The protein level of SOCS3 was obviously reduced in bone cancer group.The PWT and PWL were higher than those of LV-NC group at two weeks after intrathecal injection of LV-SOCS3 but not at the time of one week after injection.SOCS3 could be significantly increased and NF-?B reduced in L2-L5 DRGs at one week after intrathecal LV-SOCS3 injection,but no change in P2X3 R protein level was observed.At two weeks after intrathecal injection of LV-SOCS3,the protein level of NF-?B was maintained at low level and P2X3 R protein level was also significantly reduced.Conclusion:Intrathecal injection of LV-SOCS3 could modulate the expression of NF-?B and P2X3 R in bone cancer pain rats,and the alleviation of bone cancer pain may be achieved by regulating the expression of P2X3 R.