Infiltrated Macrophages Aggravate TMJOA Chronic Pain via Piezo2 in IB4+-TG Neurons.

IF 2.9 3区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Oral diseases Pub Date : 2025-06-01 Epub Date: 2025-03-06 DOI:10.1111/odi.15304
Xueke Jia, Xin Liu, Taomin Zhu, Xiaohan Ma, Ruiming Chen, Huimin Li, Yaping Feng, Liwu Zheng, Yu Liu, Jin Ke
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Abstract

Objective: Recent research indicates that macrophages in ganglia are linked to chronic pain, with Piezo2 ion channels playing a key role in pain sensation. Our study aims to elucidate the interplay between macrophages and Piezo2 in temporomandibular joint osteoarthritis (TMJOA) chronic pain.

Materials and methods: We induced TMJOA chronic pain in rats via articular injection of monosodium iodoacetate (MIA). We then depleted macrophages using clodronate liposomes and overexpressed Piezo2 in trigeminal ganglion (TG) neurons with adeno-associated virus 9 (AAV9)-Piezo2 in TMJOA rats. To explore the connection between macrophages and Piezo2, we employed immunofluorescence, in vitro studies, and the Rat Grimace Scale (RGS) to evaluate pain thresholds in TMJOA rats.

Results: A positive correlation was observed between macrophage infiltration and Piezo2 upregulation in TG neurons of TMJOA rats. Depletion of infiltrated macrophages downregulated Piezo2 in TG neurons, while Piezo2 overexpression negated the pain-relieving effects of infiltrated macrophage depletion in TMJOA rats. Macrophages primarily influenced Piezo2 expression in IB4 + - TG neurons of TMJOA chronic pain rats. Ex vivo studies revealed that infiltrated macrophage-derived IL-1β and TNF-α cytokines activate Dil + -TG neurons by upregulating Piezo2 in TMJOA rats.

Conclusions: Infiltrated macrophages exacerbate MIA-induced TMJOA chronic pain by upregulating Piezo2 expression in IB4+-TG neurons.

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浸润性巨噬细胞通过IB4+-TG神经元中的Piezo2加重TMJOA慢性疼痛。
目的:最近的研究表明神经节巨噬细胞与慢性疼痛有关,其中Piezo2离子通道在疼痛感觉中起关键作用。我们的研究旨在阐明巨噬细胞和Piezo2在颞下颌关节骨关节炎(TMJOA)慢性疼痛中的相互作用。材料与方法:通过关节注射碘乙酸钠(MIA)诱导大鼠TMJOA慢性疼痛。然后,我们用氯膦酸脂体消耗巨噬细胞,用腺相关病毒9 (AAV9)-Piezo2在TMJOA大鼠三叉神经节(TG)神经元中过表达Piezo2。为了探讨巨噬细胞与Piezo2之间的关系,我们采用免疫荧光、体外研究和大鼠鬼脸量表(RGS)来评估TMJOA大鼠的疼痛阈值。结果:巨噬细胞浸润与TMJOA大鼠TG神经元中Piezo2表达上调呈正相关。在TMJOA大鼠中,浸润性巨噬细胞耗竭可下调TG神经元中Piezo2的表达,而过表达的Piezo2则可消除浸润性巨噬细胞耗竭对疼痛的缓解作用。巨噬细胞主要影响慢性疼痛大鼠IB4 + - TG神经元中Piezo2的表达。离体研究表明,巨噬细胞来源的IL-1β和TNF-α细胞因子通过上调Piezo2激活TMJOA大鼠的Dil + -TG神经元。结论:浸润的巨噬细胞通过上调IB4+-TG神经元中Piezo2的表达而加重mia诱导的TMJOA慢性疼痛。
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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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