Lenert Melissa E, Green Audrey R, Merriwether Ericka N, Burton Michael D
Neuroimmunology and Behavior Laboratory, Department of Neuroscience, School of Behavioral and Brain Sciences, Center for Advanced Pain Studies, University of Texas at Dallas, 800 W. Campbell Road, Richardson, TX 75080, USA.
Inclusive and Translational Research in Pain Lab Department of Physical Therapy Steinhardt School of Culture, Education, and Human Development New York University 380 Second Avenue, 4th Floor New York, NY 10012, USA.
Neurobiol Pain. 2024 Oct 16;16:100169. doi: 10.1016/j.ynpai.2024.100169. eCollection 2024 Jul-Dec.
Fibromyalgia (FM) is a complex chronic musculoskeletal pain disorder with an elusive pathogenesis, with a strong implication of immune interactions. We recently found that IL-5 and the adaptive immune system mediates pain outcomes in fibromyalgia (FM) patients and preclinical models of FM-like chronic widespread pain (CWP). However, there is an active debate if FM/CWP has an autoimmune etiology. Preclinical models of CWP utilize a repeated insult paradigm, which resembles a primary, then secondary response similarly observed in the antibody response, in which the subsequent event causes a potentiated pain response. Recent translational studies have implicated immunoglobulins (Ig) and B-cells in FM/CWP pathophysiology. To understand if these are involved in preclinical models of CWP, we performed comprehensive B-cell phenotyping in the bone marrow, circulation, and popliteal (draining) lymph nodes in the two-hit acidic saline model of CWP. We found increased MHC class II-expressing B-cells in peripheral blood, increased activated plasma cells in peripheral blood, and increased memory B-cells in the bone marrow. Interestingly, acidic pH (4.0) injected mice have reduced levels of IgG1, independent of treatment with IL-5. We have demonstrated that the acidic saline model of CWP induces T-cell mediated activation of B-cells, increased active plasma cells, and increased memory B-cells in female mice.
纤维肌痛（FM）是一种复杂的慢性肌肉骨骼疼痛疾病，其发病机制难以捉摸，与免疫相互作用密切相关。我们最近发现，白细胞介素-5（IL-5）和适应性免疫系统介导了纤维肌痛（FM）患者以及FM样慢性广泛性疼痛（CWP）临床前模型中的疼痛结果。然而，关于FM/CWP是否具有自身免疫病因存在着激烈的争论。CWP的临床前模型采用重复损伤范式，这类似于在抗体反应中观察到的初次反应，然后是二次反应，其中后续事件会导致增强的疼痛反应。最近的转化研究表明免疫球蛋白（Ig）和B细胞参与了FM/CWP的病理生理学过程。为了了解它们是否参与CWP的临床前模型，我们在CWP的双次打击酸性盐水模型中，对骨髓、循环系统和腘窝（引流）淋巴结进行了全面的B细胞表型分析。我们发现外周血中表达主要组织相容性复合体II类（MHC II）的B细胞增加，外周血中活化浆细胞增加，骨髓中记忆B细胞增加。有趣的是，注射酸性pH值（4.0）的小鼠IgG1水平降低，这与IL-5治疗无关。我们已经证明，CWP酸性盐水模型可诱导雌性小鼠中T细胞介导的B细胞活化、活性浆细胞增加和记忆B细胞增加。
