Sexual Dimorphism in Mechanical Hypersensitivity Induced by Subcutaneous Injection of M-CSF
10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.2023.0305
- VernacularTitle: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
- Author:
Xiang-ge PENG
1
;
Zhen-jia LIN
1
;
Hui ZHANG
2
;
Shi-ze LENG
2
;
Yuan TANG
1
;
Yu-fan ZHENG
1
;
Zhi TAN
1
;
Li-jun ZHOU
1
Author Information
1. Department of Physiology， Zhongshan School of Medicine， Sun Yat-sen University//Center for Pain Research， Sun Yat-sen University， Guangzhou 510080， China
2. Department of Anesthesiology， Guangdong Second People's Hospital， Guangzhou 510317， China
- Publication Type:Journal Article
- Keywords:
pain hypersensitivity;
sexual dimorphism;
macrophage;
macrophage colony-stimulating factor;
calcitonin gene-related peptide
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2023;44(3):395-402
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo 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. MethodsThirty 10-week-old C57BL/6J mice were randomly divided into three groups， (n = 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 （p-ERK） in L5-L6 DRG and lumbar spinal dorsal horn. ResultsIn 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 p-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 p-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. ConclusionSubcutaneous 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.
