上海交通大学学报(医学版) ›› 2019, Vol. 39 ›› Issue (5): 463-.doi: 10.3969/j.issn.1674-8115.2019.05.005

• 论著·基础研究 • 上一篇    下一篇

趋化因子 CCL2对骨癌痛大鼠痛行为的影响及其外周机制

王丽娅 1,高坡 2,周晔 1   

  1. 1. 上海交通大学医学院附属国际和平妇幼保健院妇产科,上海市胚胎源性疾病重点实验室,上海市临床重点专科(建设项目)—“强主体”妇产科,上海 200030;2. 上海交通大学医学院附属仁济医院麻醉科,上海 200127
  • 出版日期:2019-05-28 发布日期:2019-07-26
  • 通讯作者: 周晔,电子信箱:victoriazhou66@163.com。
  • 作者简介:王丽娅(1985—),女,住院医师,硕士;电子信箱: annya1985010@sina.com。
  • 基金资助:
    国家自然科学基金青年科学基金项目(81800748)

Effects of CC chemokine ligand 2 on pain behavior in a rat model of bone cancer pain and its underlying peripheral mechanism

WANG Li-ya1, GAO Po2, ZHOU Ye1   

  1. 1. Department of Gynaecology and Obstetrics, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine; Shanghai Key Laboratory of Embryo Original Diseases; Shanghai Municipal Key Clinical Specialty, Shanghai 200030, China; 2. Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
  • Online:2019-05-28 Published:2019-07-26
  • Supported by:
    National Natural Science Foundation of China, 81800748

摘要: 目的 ·研究 CC趋化因子配体 2(CC chemokine ligand 2,CCL2)对骨癌痛( bone cancer pain,BCP)大鼠痛行为的影响及其外周机制。方法 ·在 SD大鼠右侧后肢胫骨骨髓腔内注入 Walker256乳腺癌细胞,建立 BCP模型,假手术组注射等体积的生理盐水。检测 BCP大鼠机械痛阈值,来判断 BCP模型是否成功。采用免疫荧光染色的方法,检测 2组大鼠 L4和 L5背根神经节( dorsal root ganglion,DRG)中 CCL2的表达情况。术侧足底注射 CCL2(500 ng,25 μL),观察对 2组大鼠术侧后肢抬腿和舔脚行为的影响。采用全细胞膜片钳的方法,考察 CCL2对 2组大鼠急性分离培养的 DRG神经元膜电位的影响。结果 ·术后 14 d,BCP大鼠的机械刺激痛阈显著低于假手术组;其术侧 L4和 L5 DRG中 CCL2的表达明显高于假手术组;足底注射 CCL2后,BCP大鼠右后肢的悬空时间显著多于假手术组; CCL2引起 BCP大鼠 DRG神经元去极化的比例和幅度均显著高于假手术组。结论 · CCL2可易化 BCP大鼠痛行为,其外周机制可能由 CCL2诱导 DRG神经元去极化,进而增强神经元兴奋性,提示 CCL2在 BCP的发生发展中发挥重要作用。

关键词: CC趋化因子配体 2, 骨癌痛, 背根神经节, 膜电位, 去极化

Abstract:

Objective · To investigate the effects of CC chemokine ligand 2 (CCL2) on pain behavior in a rat model of bone cancer pain (BCP) and the underlying peripheral mechanisms. Methods · BCP models were developedinoculation of Walker256 mammary gland carcinoma cells into the tibia medullary cavities of right hind limbs SD rats. The same volume of saline was injected in sham operation (sham) group. The mechanical pain threshold was measured to judge the success of BCP model. Expression of CCL2 in L4 and L5 dorsal root ganglion (DRG) was detectedimmunofluorescence staining. CCL2 (500 ng, 25 μL) was injected into plantar of the operated side to observe its effects on leg-raising and foot-licking behaviors of hind paws in BCP and sham rats. Whole-cell patch-clamp recording was used to investigate the effects of CCL2 on membrane potential of acutely dissociated DRG neurons the two groups. Results · Fourteen days after operation, the mechanical pain threshold in the right hind paws of BCP rats was significantly lower than that in sham rats. Compared with the Sham rats, the of CCL2 in L4 and L5 DRG of BCP rats was significantly higher. Plantar injection of CCL2 increased paw lift time in BCP rats. The rate and amplitude of depolarization inducedCCL2 in BCP DRG neurons were significantly higher than those in sham neurons. Conclusion · CCL2 facilitates pain behavior in BCP rats, and its peripheral mechanism maybe involves CCL2-induced neuron depolarization to enhance excitability of DRG neurons. These results indicate that CCL2 plays an important role in development of BCP.

Key words: CC chemokine ligand 2, bone cancer pain, dorsal root ganglion, membrane potential, depolarization

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