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目的研究脊髓组织神经化学物质谷氨酸(glutamate,Glu)、γ-氨基丁酸(γ-aminobutyric acid,GABA)及大脑皮质内P物质(substance P,SP)和强啡肽A1-13(dynorphin A1-13,Dyn A1-13)在癌症侵袭镜像痛中的作用及加巴喷丁对其影响。方法雄性BALB/c小鼠随机分为正常组、操作对照组(注射0.2 m L灭活的S180肉瘤细胞液)、模型组(于右腿股骨大转子处注射0.2 m L S180肉瘤细胞液)和加巴喷丁组(0.2 m L S180肉瘤细胞液+120 mg/kg加巴喷丁,ip),造模前及术后分别用Von Frey纤维丝测定术侧及对侧后足的机械痛阈值;采用高效液相-荧光法检测脊髓L3-L5节段内Glu、GABA浓度;放射免疫法检测大脑皮质内SP、Dyn A1-13的含量。结果伴随术侧癌症侵袭痛的产生,模型组小鼠术侧的镜像部位出现了与术侧发展趋势相同、程度近似的机械痛阈下降。模型组小鼠脊髓内Glu及大脑皮质内SP水平均显著升高(P<0.05,P<0.01),而脊髓内GABA及大脑皮质内Dyn A1-13的含量均显著降低(P<0.05);加巴喷丁给药后小鼠双侧的机械痛阈值均显著升高,可持续240 min(P<0.05,P<0.01),并逆转了癌症侵袭镜像痛小鼠中枢神经系统内上述神经化学物质的改变(P<0.01或P<0.05)。结论 S180肉瘤细胞所致癌症侵袭痛模型小鼠存在镜像痛现象,脊髓内Glu、GABA及大脑皮质中SP、Dyn A1-13可能参与癌症侵袭镜像痛的发生和维持机制,加巴喷丁通过这一机制对癌症侵袭镜像痛模型小鼠发挥镇痛作用。
Objective To investigate the effects of neurochemicals such as glutamate (Glu), γ-aminobutyric acid (GABA) and substance P (SP) in cerebral spinal cortex and dynorphin A1-13, Dyn A1-13) in the mirror-like pain of cancer invasion and the effect of gabapentin on it. Methods Male BALB / c mice were randomly divided into normal group, operation control group (injection of 0.2 m L inactivated S180 sarcoma cell fluid), model group (0.2 m L S180 sarcoma fluid injected into the right trochanter) Gabapentin group (0.2 m L S180 sarcoma cell fluid + 120 mg / kg gabapentin, ip). The mechanical pain threshold of both the contralateral and contralateral hindpaw was measured by Von Frey filament before and after the operation. The concentrations of Glu and GABA in the L3-L5 segment of spinal cord were detected by fluorometry. The levels of SP and Dyn A1-13 in the cerebral cortex were detected by radioimmunoassay. Results With the occurrence of invasion pain in the operation side of the cancer, the mechanical pain threshold of the model group was similar to that of the operation side in the operation side of the model group. Spinal levels of Glu and cortical SP in model group were significantly increased (P <0.05, P <0.01), while contents of GABA in spinal cord and Dyn A1-13 in cerebral cortex were significantly decreased (P <0.05). The mechanical thresholds of both sides of mice treated with gabapentin significantly increased for 240 min (P <0.05, P <0.01), and reversed the change of neurochemicals in the central nervous system of mice with cancer invasion mirror pain (P <0.01 or P <0.05). Conclusions Mice with tumor-induced pain induced by S180 sarcoma have mirror pain phenomenon. Spinal cord glutamatergine, GABA and SP and Dyn A1-13 in the cerebral cortex may be involved in the occurrence and maintenance mechanism of cancer invasion mirror pain. By this mechanism, Cancer invasion mirrors pain model mice exert analgesic effects.