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目的:研究CQ复方对大鼠骨癌痛模型的痛觉敏化干预作用及其相关机制。方法:将雌性Wistar大鼠随机分为假手术组和手术组,分别进行操作对照和Walker-256乳腺癌细胞移植于胫骨的转移性癌痛造模手术。将造模成功的40只大鼠随机分为模型组,CQ复方高、中、低剂量组(200,150,100 mg·kg~(-1))及加巴喷丁组(100 mg·kg~(-1)),每组8只大鼠。以Von frey纤维丝测定的机械缩足阈值(mechanical withdrawal threshold,MWT)作为大鼠疼痛行为学评价指标;采用微透析分析仪检测脑脊液内谷氨酸(glutamate,Glu),放射免疫法检测脊髓L4~L6节段内P物质(substance P,SP)及β-内啡肽(β-endorphin,β-EP)含量;采用Aim Plex流式高通量多因子检测技术分析肿瘤局部组织中白细胞介素-12(interleukin-12,IL~(-1)2-P70),神经生长因子(β-nerve growth factor,β-NGF)含量。结果:与模型组相比,CQ复方各组及加巴喷丁组均明显提高了大鼠的MWT,前者投药30 min后MWT上升,60 min升高最明显(P<0.05,P<0.01),CQ复方高、中、低剂量组之间其阈值升高呈量效依赖关系,且连续3 d投药的镇痛效果强于第1次投药;与模型组相比,CQ复方及加巴喷丁降低了骨癌痛模型大鼠脑脊液中Glu,脊髓L4~L6节段中SP,β-EP和肿瘤局部组织中β-NGF水平(P<0.05),提高了IL~(-1)2-P70的浓度(P<0.05)。结论:CQ复方具有干预骨癌痛大鼠痛觉敏化行为学指标的作用,强度与加巴喷丁相似;其机制可能与抑制中枢内兴奋性氨基酸类神经递质Glu,肽类神经调质SP,β-EP及周围组织β-NGF的水平、并促进机体免疫反应的IL~(-1)2-P70有关。
Objective: To study the effect of CQ compound on hyperalgesia in rat bone cancer pain model and its related mechanism. METHODS: Female Wistar rats were randomly divided into sham-operation group and operation group. The control and Walker-256 breast cancer cells were transplanted in the tibia for metastatic cancer pain surgery. The 40 successful rats were randomly divided into model group, CQ compound high, middle and low dose groups (200, 150, 100 mg · kg -1) and gabapentin group (100 mg · kg -1) 8 rats in each group. Mechanical withdrawal threshold (MWT) measured by Von frey filaments was used to evaluate the pain behavior of rats. Glutamate (Glu) in cerebrospinal fluid was detected by microdialysis analyzer and radioactive immunohistochemical method was used to detect spinal cord L4 The levels of substance P (SP) and β-endorphin (β-EP) in the segments of ~ L6 were measured. Aim Plex flow cytometry was used to detect the levels of interleukin -12 (IL-1) 2-P70 and the content of β-nerve growth factor (β-NGF). Results: Compared with the model group, the MWT of rats in CQ group and gabapentin group increased significantly. The MWT of the former increased 30 min after administration, and the MWT increased most significantly at 60 min (P <0.05, P <0.01) Compared with the model group, CQ compound and gabapentin reduced the pain model of bone cancer larger than the model group (P <0.05), and elevated the concentration of IL-2-P70 (P <0.05) .Conclusion: The level of IL-2 and P70 in the cerebrospinal fluid (CSF) . CONCLUSION: CQ has the effect of intervening hyperalgesia sensory index in rats with bone cancer pain, and its intensity may be similar to that of gabapentin. The mechanism may be related to inhibition of central neurotransmitter Glu, peptide neurotransmitter SP, EP and surrounding tissue β-NGF levels, and promote the body’s immune response to IL-1 2-P70.