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Aquaporin 4 deficiency attenuates chronic neuropathic pain,but not acute pain

【摘要】:正OBJECTIVE To study the role of AQP4 deficiency in pain and to explore its possible mechanisms.METHODS We investigated the effect of AQP4 knockout on acute pain responses by thermal(hot-plate and tail-flick tests),chemical(formalin and capsaicin tests) and mechanical(von Frey hair test) stimuli,then investigated the effect of AQP4 knockout on chronic neuropathic pain by the spared nerve injury(SNI) model.The expression of astrocytes activate related protein glial fibers acid protein(GFAP) was analyzed by western blot and the content of proinflammatory cytokines(TNF-α,IL-1βand IL-6) in spinal cord were detected by ELISA.RESULTS(1) Effects of AQP4 deficiency on acute pain and chronic neuropathic pain.In the tail-flick and hot-plate tests, two acute pain models of thermal stimuli,the latency of licking hindpaw or tail flick had no differences between wild type(WT) and AQP4 knockout(KO) mice.In capsaicin and formalin tests,two models of chemical stimuli,the durations of licking injected hind-paws had no differences between WT and KO mice.In the von Frey hair test,a model of mechanical sitimuli,no significant difference in 50%PWT was found between these two genotypes mice as well.In the SNI model,a chronic neuropathic pain model,a significant attenuation in mechanical allodynia were detected in KO mice compared with WT mice(P0.01).These results indicated that AQP4 deficiency attenuated chornic neuropathic pain,but not thermal,chemical or mechanical-stimulated acute pain.(2) The possible mechanism of AQP4 deficiency attenuating chronic neuropathic pain.In the SNI model,compared with WT-Sham group,the GFAP protein level in the spinal cord was significantly increased in WT-SNI group;however,no difference in the GFAP protein level in the spinal cord was detected between KO-SNI and KO-Sham groups.In addition,the contents of TNF-αand IL-6,but not IL-1β,in the spinal cord were increased in WT-SNI group,while the contents of these two proinflammatory cytokines had no differences between KO-SNI and KO-Sham mice.CONCLUSION AQP4 deficiency attenuated chornic neuropathic pain,but not acute pain,which might be due to the suppression of astrocytes activation and proinflammatory cytokines release in the spinal cord during neuropathic pain.

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