Fibroblasts: the neglected cell type in peripheral sensitisation and chronic pain? A review based on a systematic search of the literature.
Fibroblasts: the neglected cell type in peripheral sensitisation and chronic pain? A review based on a systematic search of the literature.
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DOI：
10.1136/bmjos-2021-100235
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Denk F
中科院分区：
文献类型：
--
作者：
Shinotsuka N;Denk F
慢性疼痛及其潜在的生物学机制已经被研究了几十年，已知有无数的分子、受体和细胞类型与异常痛感有关。除了神经元的明显作用外，小胶质细胞、巨噬细胞和T细胞等免疫细胞也是持续性疼痛的重要驱动因素。因此，虽然神经炎症在疼痛研究中得到了广泛的研究，但有一种细胞类型在这方面似乎相当被忽视：不起眼的成纤维细胞。成纤维细胞可能看起来很低调，但实际上在调节免疫细胞功能和推动慢性炎症方面发挥着重要作用。在这里，我们的目标是确定与成纤维细胞在慢性疼痛条件和模型中有关的研究的广度和质量。我们着手分析目前关于这一主题的文献--使用系统的筛选和数据提取方法，以获得对已发表的内容的平衡看法。我们对纳入的文章进行了分类--根据调查的内容、结果的估计质量和任何共同的结论对它们进行分层。我们发现，在这一领域的研究令人惊讶地很少：134篇文章符合我们的纳入标准，其中只有极少数直接研究了成纤维细胞与外周神经元之间的相互作用。成纤维细胞是一种普遍存在的细胞类型，是多种组织中多种前痛介质的重要来源。我们认为它们应该在疼痛研究中发挥更核心的作用，并提出了一个新的、可测试的模型，说明成纤维细胞如何驱动外周神经元敏化。
Chronic pain and its underlying biological mechanisms have been studied for many decades, with a myriad of molecules, receptors and cell types known to contribute to abnormal pain sensations. Besides an obvious role for neurons, immune cells like microglia, macrophages and T cells are also important drivers of persistent pain. While neuroinflammation has therefore been widely studied in pain research, there is one cell type that appears to be rather neglected in this context: the humble fibroblast. Fibroblasts may seem unassuming but actually play a major part in regulating immune cell function and driving chronic inflammation. Here, our aim was to determine the breadth and quality of research that implicates fibroblasts in chronic pain conditions and models. We set out to analyse the current literature on this topic—using systematic screening and data extraction methods to obtain a balanced view on what has been published. We categorised the articles we included—stratifying them according to what was investigated, the estimated quality of results and any common conclusions. We found that there has been surprisingly little research in this area: 134 articles met our inclusion criteria, only a tiny minority of which directly investigated interactions between fibroblasts and peripheral neurons. Fibroblasts are a ubiquitous cell type and a prominent source of many proalgesic mediators in a wide variety of tissues. We think that they deserve a more central role in pain research and propose a new, testable model of how fibroblasts might drive peripheral neuron sensitisation.