Effects of N-methyl-D-aspartate Receptor in Keratinocyte on TypeⅠComplex Regional Pain Syndrome / 中国医学科学院学报

ABSTRACT

To observe the cell origin of N-methyl-D-aspartic acid(NMDA)receptor expression in skin after chronic ischemic pain modeling in rats and explore the role of NMDA receptor in type Ⅰ complex regional pain syndrome. Forty-two adult male Sprague-Dawley rats were randomly divided into five groupssham operation group(=12),chronic post ischemia pain(CPIP)group(=12),CPIP+normal saline(NS)group(=6),CPIP+NMDA group(=6),and CPIP+MK801 group(=6).Six rats in the sham operation group and CPIP group were sacrificed under deep anesthesia one day after modeling.The plantar skin and L3-L5 spinal cord tissue were used for NR1(NMDA receptor)subunit immunofluorescence detection and for Western blotting of NR1,interleukin(IL)-1β,and tumor necrosis factor(TNF)-α.For the remaining rats,the mechanical withdrawal threshold(MWT)values on the 2nd,6th,10th and 14th day after ischemia were recorded,and the corresponding drugs were injected subcutaneously from the 6th day after ischemia.The skin and L3-L5 spinal cords were collected on the 14th day,and the same detection methods were applied. Compared with the sham operation group,the CPIP group had significantly higher expressions of NR1(1.708±0.064;=12.120, <0.001),IL-1β(2.575±0.305;=5.158, =0.003),and TNF-α(2.691±0.217;=7.786, <0.001)in the skin on the first day after modeling.After intervention with NMDA and MK801,the MWT value was [(20.37±0.95)g] in the CPIP+NS group,which was significantly higher than that in CPIP+NMDA group [(15.85±1.09)g;=10.920, <0.001] but significantly lower than that in CPIP+MK801 group[(22.95±0.96)g;=6.421, <0.001] 10 days after modeling.On the 14th day,compared with the MWT of the CPIP+NS group [(21.57±0.96)g],the CPIP+NMDA group had significantly decreased MWT value [(16.53±1.63)g;=12.190, <0.001],and the CPIP+MK801 group had significantly increased MWT value [(23.27±1.28)g;=4.094, =0.025].Compared with the sham operation group,the CPIP group had significantly increased NR1 expression(1.708±0.064;=10.910, <0.001)and the CPIP+NS group had significantly increased expressions of IL-1β(2.518±0.147;=11.010, <0.001)and TNF-α(1.949±0.184;=10.870, <0.001).Compared with the CPIP+NS group,the CPIP+NMDA group had significantly increased expressions of IL-1β(4.816±0.607;=16.670, =0.003)and TNF-α(2.629±0.349;=7.790, <0.001)and the CPIP+MK801 group had significantly decreased expressions of IL-1β(1.048±0.257;=10.660, =0.003)and TNF-α(0.790±0.165;=13.280, <0.001). NMDA receptor activation in skin keratinocytes after chronic ischemia in rats hinders the expression of inflammatory cytokines such as IL-1β and TNF-α,which may be involved in central sensitization and pain conduction of type Ⅰ complex regional pain syndrome.