实验性自身免疫性脑脊髓炎
医学
痛觉超敏
髓鞘少突胶质细胞糖蛋白
背根神经节
免疫学
组织蛋白酶G
中性粒细胞胞外陷阱
炎症
中性粒细胞弹性蛋白酶
过继性细胞移植
髓过氧化物酶
神经病理性疼痛
弹性蛋白酶
痛觉过敏
内科学
多发性硬化
伤害
药理学
受体
化学
T细胞
脊髓
免疫系统
酶
精神科
生物化学
作者
Yuka Harada,Jing Zhang,Kazuhisa Imari,Ryo Yamasaki,Junjun Ni,Zhou Wu,Kenji Yamamoto,Jun Ichi Kira,Hiroshi Nakanishi,Yoshinori Hayashi
出处
期刊:Pain
[Ovid Technologies (Wolters Kluwer)]
日期:2019-09-01
卷期号:160 (9): 2050-2062
被引量:13
标识
DOI:10.1097/j.pain.0000000000001596
摘要
Pain is a frequent and disabling symptom in patients with multiple sclerosis (MS); however, the underlying mechanisms of MS-related pain are not fully understood. Here, we demonstrated that cathepsin E (CatE) in neutrophils contributes to the generation of mechanical allodynia in experimental autoimmune encephalomyelitis, an animal model of MS. We showed that CatE-deficient (CatE) mice were highly resistant to myelin oligodendrocyte glycoprotein (MOG35-55)-induced mechanical allodynia. After MOG35-55 immunization, neutrophils immediately accumulated in the dorsal root ganglion (DRG). Adoptive transfer of MOG35-55-stimulated wild-type neutrophils into the dorsal root ganglion induced mechanical allodynia in the recipient C57BL/6 mice. However, the pain threshold did not change when MOG35-55-stimulated CatE neutrophils were transferred into the recipient C57BL/6 mice. MOG35-55 stimulation caused CatE-dependent secretion of elastase in neutrophils. Behavioral analyses revealed that sivelestat, a selective neutrophil elastase inhibitor, suppressed mechanical allodynia induced by adoptively transferred MOG35-55-stimulated neutrophils. MOG35-55 directly bound to toll-like receptor 4, which led to increased production of CatE in neutrophils. Our findings suggest that inhibition of CatE-dependent elastase production in neutrophil might be a potential therapeutic target for pain in patients with MS.
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