ABSTRACT
Objective: To investigate the effect of aquaporin 4(AQP4)in neuropathic pain and explore the rela- tionship with the activation of spinal astrocytes and release of proinflammatory cytokines. Methods: The effect of AQP4 gene knockout(KO)on the pain-related behavior was investigated using the sciatic nerve branch injury model(SNI)of AQP4 KO and wild type(WT)mice. The expression of astrocyte activation-related protein,glial fibrillary acidic protein(GFAP),and the level of proinflammatory cytokines,TNF-α and IL-6,all in the mouse spinal cord samples,were detect- ed by Western blot(WB)and ELISA,respectively. Results: After SNI surgery,compared with the WT group,a signifi- cant attenuation in mechanical allodynia was found in the KO group(P<0.01),however,no difference was detected be- tween two sham groups(Sham)of WT and KO mice(P>0.05). These results indicated that the AQP4 gene knockout re- lieved neuropathic pain. Fouteen days after SNI surgery,WB results showed that the GFAP level in mouse spinal cord was significantly higher in the WT-SNI group than in the WT-Sham group(P<0.01),whereas the GFAP level in the KOSNI group was significantly lower than that in the WT-SNI group(P<0.01). These results indicated that AQP4 KO inhib- ited activation of spinal astrocytes in SNI model mice. In addition,14 days after SNI surgery,ELISA results showed that the levels of mouse spinal cord proinflammatory cytokines,TNF-α and IL-6 in the WT-SNI group were significantly high- er than those in the WT-Sham group(P<0.05 and P<0.01,respectively),whereas the levels of TNF-α and IL-6 in the KO-SNI group were significantly lower than those in the WT-SNI group(P<0.05 and P<0.01,respectively). These re- sults indicated that AQP4 KO inhibited the level of mouse spinal cord proinflammatory cytokines in SNI model mice. Conclusion: The AQP4 gene knockout may relieve the neuropathic pain via the inhibition of the astrocyte activation and proinflammatory cytokine release.
ABSTRACT
Objective To compare the effect of extinction using different methods and the subsequent reinstatement of morphine-primed on morphine-induced conditioned place preference (CPP).