Regulatory T-cells and IL-5 mediate pain outcomes in a preclinical model of chronic muscle pain.

IF 2.8 3区 医学 Q2 NEUROSCIENCES
Melissa E Lenert, Thomas A Szabo-Pardi, Michael D D Burton
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引用次数: 3

Abstract

Fibromyalgia (FM) is a chronic musculoskeletal pain disorder primarily diagnosed in women. Historically, clinical literature focusing on cytokines and immune cells has been inconsistent. However, recent key studies show several layers of immune system dysfunction in FM. Preclinically, studies of the immune system have focused on monocytes with little focus on other immune cells. Importantly, T-cells are implicated in the development and resolution of chronic pain states, particularly in females. Our previous work showed that monocytes from women with FM produced more interleukin 5 (IL-5) and systemic treatment of IL-5 reversed mechanical hypersensitivity in a preclinical model of FM. Typically, IL-5 is produced by TH2-cells, so in this study we assessed T-cell populations and cytokine production in female mice using the acid-induced chronic muscle pain model of FM before and after treatment with IL-5. Two unilateral injections of pH4.0 saline, five days apart, into the gastrocnemius muscle induce long-lasting widespread pain. We found that peripheral (blood) regulatory Thelper-cells (CD4+ FOXP3+) are downregulated in pH4.0-injected mice, with no differences in tissue (lymph nodes) or CD8+ T-cell populations. We tested the analgesic properties of IL-5 using a battery of spontaneous and evoked pain measures. Interestingly, IL-5 treatment induced place preference in mice previously injected with pH4.0 saline. Mice treated with IL-5 show limited changes in T-cell populations compared to controls, with a rescue in regulatory T-cells which positively correlates with improved mechanical hypersensitivity. The experiments in this study provide novel evidence that downregulation of regulatory T-cells play a role in chronic muscle pain pathology in the acidic saline model of FM and that IL-5 signaling is a promising target for future development of therapeutics.

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调节性t细胞和IL-5介导慢性肌肉疼痛临床前模型的疼痛结果。
纤维肌痛(FM)是一种慢性肌肉骨骼疼痛疾病,主要诊断为女性。历史上,关注细胞因子和免疫细胞的临床文献一直不一致。然而,最近的关键研究表明,FM中存在多层免疫系统功能障碍。临床前,免疫系统的研究主要集中在单核细胞上,很少关注其他免疫细胞。重要的是,t细胞与慢性疼痛状态的发展和消退有关,特别是在女性中。我们之前的研究表明,FM女性的单核细胞产生更多的白细胞介素5 (IL-5), IL-5的全身治疗逆转了FM临床前模型中的机械超敏反应。通常,IL-5是由th2细胞产生的,因此在本研究中,我们使用IL-5治疗前后的FM酸致慢性肌肉疼痛模型来评估雌性小鼠的t细胞数量和细胞因子的产生。两次单侧注射pH4.0生理盐水,间隔5天,进入腓肠肌引起持久的广泛疼痛。我们发现外周(血液)调节细胞(CD4+ FOXP3+)在ph4.0注射小鼠中下调,在组织(淋巴结)或CD8+ t细胞群中没有差异。我们使用一系列自发疼痛和诱发疼痛措施测试了IL-5的镇痛特性。有趣的是,IL-5处理在先前注射pH4.0生理盐水的小鼠中诱导了位置偏好。与对照组相比,接受IL-5治疗的小鼠的t细胞群变化有限,调节性t细胞的恢复与机械超敏反应的改善呈正相关。本研究的实验提供了新的证据,表明调节性t细胞的下调在FM的酸性生理盐水模型的慢性肌肉疼痛病理中起作用,IL-5信号是未来治疗方法发展的一个有希望的靶点。
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
Molecular Pain
Molecular Pain 医学-神经科学
CiteScore
5.60
自引率
3.00%
发文量
56
审稿时长
6-12 weeks
期刊介绍: Molecular Pain is a peer-reviewed, open access journal that considers manuscripts in pain research at the cellular, subcellular and molecular levels. Molecular Pain provides a forum for molecular pain scientists to communicate their research findings in a targeted manner to others in this important and growing field.
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