Autoantibodies cause nociceptive sensitization in a mouse model of degenerative osteoarthritis.

IF 5.9 1区 医学 Q1 ANESTHESIOLOGY
Tian-Zhi Guo, Xiaoyou Shi, Xuanying Li, Wen-Wu Li, Tzuping Wei, Peyman Sahbaie, Tiffany N McAllister, Martin S Angst, J David Clark, Wade S Kingery
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Abstract

Abstract: Previous preclinical and translational studies suggest that tissue trauma related to bony fracture and intervertebral disk disruption initiates the formation of pronociceptive antibodies that support chronic musculoskeletal pain conditions. This study tested this hypothesis in the monosodium iodoacetate (MIA) mouse model of osteoarthritis (OA) and extended the findings using OA patient samples. Monosodium iodoacetate was injected unilaterally into the knees of male and female wild-type (WT) and muMT mice (lacking B cells) to induce articular cartilage damage. Repeated nociceptive behavioral testing was performed, and serum was collected for antibody isolation and passive transfer experiments. Serum antibodies collected from patients with OA were tested in MIA-treated muMT mice. Biochemical analyses were performed on knee joint tissues. Monosodium iodoacetate-treated WT mice developed chronic ipsilateral hindlimb allodynia, hyperalgesia, and unweighting, but these pain behaviors were absent in MIA-treated muMT mice, indicating that cartilage injury-induced pain is B-cell dependent. IgM accumulation was observed in the knee tissues of MIA-treated mice, and intra-articular injection of IgM from MIA-treated mice into MIA-treated muMT mice caused nociceptive sensitization. Similarly, intra-articular injection of IgM from patients with OA was pronociceptive in muMT MIA mice and control subject IgM had no effect. Monosodium iodoacetate-injected joints demonstrate elevated levels of complement component 5a (C5a) and C5a receptor blockade using intra-articular PMX-53-reduced sensitization. These data suggest that MIA-treated mice and patients with OA generate pronociceptive antibodies, and further support the pronociceptive autoimmunity hypothesis for the transition from tissue injury to chronic musculoskeletal pain.

自身抗体引起退行性骨关节炎小鼠模型的伤害性致敏。
摘要:以往的临床前研究和转化研究表明,与骨骨折和椎间盘破裂相关的组织创伤启动了支持慢性肌肉骨骼疼痛的前感觉抗体的形成。本研究在碘乙酸钠(MIA)骨关节炎(OA)小鼠模型中验证了这一假设,并使用OA患者样本扩展了研究结果。将碘乙酸钠单侧注射于雄性和雌性野生型(WT)和muMT小鼠膝关节(缺乏B细胞),诱导关节软骨损伤。反复进行伤害性行为测试,采集血清进行抗体分离和被动转移实验。从OA患者收集的血清抗体在mia治疗的muMT小鼠中进行检测。膝关节组织进行生化分析。碘乙酸钠处理的WT小鼠出现慢性同侧后肢异常性疼痛、痛觉过敏和体重减轻,但mia处理的muMT小鼠没有这些疼痛行为,表明软骨损伤引起的疼痛依赖于b细胞。在mia处理小鼠的膝关节组织中观察到IgM积累,并且将mia处理小鼠的IgM关节内注射到mia处理的muMT小鼠中会引起伤害性致敏。同样,骨性关节炎患者的IgM关节内注射在muMT MIA小鼠中具有前瞻性,而对照组的IgM没有影响。碘乙酸钠注射关节显示补体成分5a (C5a)水平升高,并通过关节内pmx -53减少致敏作用阻断C5a受体。这些数据表明,mia治疗的小鼠和OA患者产生前感觉性抗体,并进一步支持了从组织损伤到慢性肌肉骨骼疼痛转变的前感觉性自身免疫假说。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
PAIN®
PAIN® 医学-临床神经学
CiteScore
12.50
自引率
8.10%
发文量
242
审稿时长
9 months
期刊介绍: PAIN® is the official publication of the International Association for the Study of Pain and publishes original research on the nature,mechanisms and treatment of pain.PAIN® provides a forum for the dissemination of research in the basic and clinical sciences of multidisciplinary interest.
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