Sexual Dimorphism in Mechanical Hypersensitivity Induced by Subcutaneous Injection of M-CSF

PENG Xiang-ge; LIN Zhen-jia; ZHANG Hui; LENG Shi-ze; TANG Yuan; ZHENG Yu-fan; TAN Zhi; ZHOU Li-jun

doi:10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2023.0305

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Sexual Dimorphism in Mechanical Hypersensitivity Induced by Subcutaneous Injection of M-CSF

Basic Research | 更新时间：2024-02-19

- Sexual Dimorphism in Mechanical Hypersensitivity Induced by Subcutaneous Injection of M-CSF
- Journal of Sun Yat-sen University(Medical Sciences) Vol. 44, Issue 3, Pages: 395-402(2023)
- 作者机构：
  
  1.中山大学中山医学院生理教研室//中山大学疼痛研究中心，广东广州 510080
  2.广东省第二人民医院麻醉科，广东广州 510317
- 作者简介：
  
  ZHOU Li-jun；E-mail：zhoulij3@mail.sysu.edu.cn
- 基金信息：
- DOI：10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2023.0305
  CLC： R441.1
- Received：06 March 2023，
  
  Published：20 May 2023
- 稿件说明：
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彭湘格,林震嘉,张辉等.皮下注射巨噬细胞集落刺激因子诱导机械痛超敏的性别二态性[J].中山大学学报（医学科学版）,2023,44(03):395-402.

PENG Xiang-ge,LIN Zhen-jia,ZHANG Hui,et al.Sexual Dimorphism in Mechanical Hypersensitivity Induced by Subcutaneous Injection of M-CSF[J].Journal of Sun Yat-sen University(Medical Sciences),2023,44(03):395-402.
彭湘格,林震嘉,张辉等.皮下注射巨噬细胞集落刺激因子诱导机械痛超敏的性别二态性[J].中山大学学报（医学科学版）,2023,44(03):395-402. DOI： 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2023.0305.

PENG Xiang-ge,LIN Zhen-jia,ZHANG Hui,et al.Sexual Dimorphism in Mechanical Hypersensitivity Induced by Subcutaneous Injection of M-CSF[J].Journal of Sun Yat-sen University(Medical Sciences),2023,44(03):395-402. DOI： 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2023.0305.

摘要

目的

通过正常小鼠皮下注射巨噬细胞集落刺激因子（M-CSF）来研究其对疼痛行为的影响是否存在性别差异，并初步探讨其机制。

方法

将30只10周龄C57 BL/6J小鼠随机分为三组（每组10只，雌雄各半）：牛血清白蛋白对照组（BSA，0.3 μg）、低剂量M-CSF组（L M-CSF，0.075 μg）、高剂量M-CSF组（H M-CSF，0.3 μg）。分别于左大腿内侧皮下注射50 μL BSA或M-CSF，每日1次，连续3 d。给药前后采用von-Frey机械敏感性测试检测各组小鼠的机械撤足阈值（PWT）。再用免疫荧光染色法观察皮肤离子钙结合衔接蛋白1（Iba1）， L5-L6 DRG及腰段脊髓背角中降钙素基因相关肽（CGRP）、磷酸化细胞外信号调节激酶（

-ERK）的表达变化。

结果

在雌性小鼠中，只有高剂量M-CSF引起显著的机械痛超敏，而在雄性小鼠中两个剂量都引起明显痛觉异常。机制上，高剂量M-CSF诱导雌性小鼠皮下巨噬细胞大量聚集（Iba1标识）；雄性小鼠巨噬细胞呈浓度依赖性增多，但没有雌性小鼠明显。在DRGs中，

-ERK与CGRP表达增多也存在类似的性别差异。值得注意的是，CGRP在雄性小鼠DRG的神经纤维中显著升高。相应地，脊髓背角浅层的

-ERK与CGRP

末梢在M-CSF处理后显著增多，且雄性小鼠多于雌性小鼠。

结论

皮下注射M-CSF诱发的机械性痛觉超敏存在性别二态性，并与外周巨噬细胞扩增和伤害性通路敏化的差异性变化有关。

Abstract

Objective

To investigate whether there exists gender differences in mechanical pain hypersensitivity induced by the subcutaneous injection of macrophage colony-stimulating factor （M-CSF） in normal mice and to explore the preliminary mechanism.

Methods

Thirty 10-week-old C57BL/6J mice were randomly divided into three groups， (

= 10 mice/group

half male and half female). The albumin control group （BSA， 0.3 μg）， low dose M-CSF group （L M-CSF， 0.075 μg） and high dose M-CSF group （H M-CSF， 0.3 μg） received 50 μL BSA or M-CSF injected subcutaneously into the left medial thigh once daily for 3 consecutive days. Before and after drug administration， von-Frey mechanical sensitivity test was used to detect the mechanical paw withdrawal threshold （PWT） in each group. Immunofluorescence was performed to examine the expression changes of Ionized calcium-binding adaptor molecule 1 (Iba1) in skin， calcitonin gene-related peptide （CGRP） and phosphorylated ERK1/2 （

-ERK） in L5-L6 DRG and lumbar spinal dorsal horn.

Results

In female mice， only high dose of M-CSF caused mechanical allodynia， whereas in male mice both doses produced marked allodynia. Mechanically， high-dose M-CSF induced massive aggregation of subcutaneous macrophages （marked by Iba1） in male and female mice， but more dramatic dependence in female mice. Similar gender differences were also found in the increase of

-ERK and CGRP expression in dorsal root ganglion （DRGs）. Notably， CGRP expression was especially elevated in the fibers of DRG in male mice. Correspondingly， the expressions of

-ERK and CGRP

terminals in the superficial spinal dorsal horn of male mice were significantly higher than those of female mice after M-CSF treatment.

Conclusion

Subcutaneous injection of M-CSF triggers sexual dimorphism in mechanical pain hypersensitivity

which is related with differential changes in peripheral macrophage expansion and sensitization of the nociceptive pathway.

关键词

Keywords

references

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