Microglia contribute to nociception via CSF-1R signaling pathway in rat orofacial carcinoma.

IF 2.9 3区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE
Oral diseases Pub Date : 2024-07-22 DOI:10.1111/odi.15077
Hui Wang, Xiaohan Peng, Ke Wu, Jinhu Sun
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Abstract

Objective: Cancer-induced pain is the most common complication of the head and neck cancer. The microglia colony-stimulating factor receptor 1 (CSF1R) plays a crucial role in the inflammation and neuropathic pain. However, the effect of CSF1R on orofacial cancer-induced pain is unclear. Here, we aimed to determine the role of CSF1R in orofacial pain caused by cancer.

Methods: We established an animal model of cancer-induced orofacial pain with Walker 256B cells. Von Frey filament test and laser-intensity pain tester were used to evaluate tumor-induced mechanical and thermal hypersensitivity. Minocycline and PLX3397 were used to alter tumor-induced mechanical and thermal hyperalgesia. Additionally, we evaluated the effect of PLX3397 on immunoinflammatory mediators and neuronal activation within the trigeminal spinal subnucleus caudalis (Vc).

Results: Walker 256B cell-induced tumor growth resulted in mechanical and thermal hyperalgesia, accompanying by microglia activation and CSF1R upregulation. Treatment with minocycline or PLX3397 reversed the associated nocifensive behaviors and microglia activation triggered by tumor. As a result of PLX3397 treatment, tumor-induced increases in pro-inflammatory cytokine expression and neuronal activation of the Vc were significantly inhibited.

Conclusions: The results of our study showed that blocking microglial activation via CSF1R may help prevent cancer-induced orofacial pain.

小胶质细胞通过 CSF-1R 信号通路促进大鼠口腔癌的痛觉反应
目的:癌症引起的疼痛是头颈部癌症最常见的并发症:癌症引起的疼痛是头颈部癌症最常见的并发症。小胶质细胞集落刺激因子受体 1(CSF1R)在炎症和神经病理性疼痛中起着至关重要的作用。然而,CSF1R 对口面部癌症诱发疼痛的影响尚不清楚。在此,我们旨在确定 CSF1R 在癌症引起的口面部疼痛中的作用:方法:我们用 Walker 256B 细胞建立了癌症诱发口面部疼痛的动物模型。方法:我们用 Walker 256B 细胞建立了癌症诱导的口面部疼痛动物模型,并使用 Von Frey 灯丝试验和激光强度疼痛测试仪来评估肿瘤诱导的机械和热超敏反应。米诺环素和 PLX3397 用于改变肿瘤诱导的机械和热超敏反应。此外,我们还评估了PLX3397对免疫炎症介质和三叉神经脊髓尾下核(Vc)内神经元激活的影响:结果:沃克256B细胞诱导的肿瘤生长导致机械和热痛,同时伴有小胶质细胞活化和CSF1R上调。米诺环素或 PLX3397 可逆转肿瘤引发的相关痛觉行为和小胶质细胞活化。PLX3397治疗的结果是,肿瘤诱导的促炎细胞因子表达和Vc神经元激活的增加受到显著抑制:我们的研究结果表明,通过CSF1R阻断小胶质细胞的活化可能有助于预防癌症诱发的口面部疼痛。
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来源期刊
Oral diseases
Oral diseases 医学-牙科与口腔外科
CiteScore
7.60
自引率
5.30%
发文量
325
审稿时长
4-8 weeks
期刊介绍: Oral Diseases is a multidisciplinary and international journal with a focus on head and neck disorders, edited by leaders in the field, Professor Giovanni Lodi (Editor-in-Chief, Milan, Italy), Professor Stefano Petti (Deputy Editor, Rome, Italy) and Associate Professor Gulshan Sunavala-Dossabhoy (Deputy Editor, Shreveport, LA, USA). The journal is pre-eminent in oral medicine. Oral Diseases specifically strives to link often-isolated areas of dentistry and medicine through broad-based scholarship that includes well-designed and controlled clinical research, analytical epidemiology, and the translation of basic science in pre-clinical studies. The journal typically publishes articles relevant to many related medical specialties including especially dermatology, gastroenterology, hematology, immunology, infectious diseases, neuropsychiatry, oncology and otolaryngology. The essential requirement is that all submitted research is hypothesis-driven, with significant positive and negative results both welcomed. Equal publication emphasis is placed on etiology, pathogenesis, diagnosis, prevention and treatment.
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