Instituto de Investigação e Inovação em Saúde da Universidade do Porto- Associação, Porto, Portugal.
Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal.
Front Immunol. 2022 Mar 10;13:812962. doi: 10.3389/fimmu.2022.812962. eCollection 2022.
Chronic pain associated with joint disorders, such as rheumatoid arthritis (RA), osteoarthritis (OA) and implant aseptic loosening (AL), is a highly debilitating symptom that impacts mobility and quality of life in affected patients. The neuroimmune crosstalk has been demonstrated to play a critical role in the onset and establishment of chronic pain conditions. Immune cells release cytokines and immune mediators that can activate and sensitize nociceptors evoking pain, through interaction with receptors in the sensory nerve terminals. On the other hand, sensory and sympathetic nerve fibers release neurotransmitters that bind to their specific receptor expressed on surface of immune cells, initiating an immunomodulatory role. Macrophages have been shown to be key players in the neuroimmune crosstalk. Moreover, macrophages constitute the dominant immune cell population in RA, OA and AL. Importantly, the targeting of macrophages can result in anti-nociceptive effects in chronic pain conditions. Therefore, the aim of this review is to discuss the nature and impact of the interaction between the inflammatory response and nerve fibers in these joint disorders regarding the genesis and maintenance of pain. The role of macrophages is highlighted. The alteration in the joint innervation pattern and the inflammatory response are also described. Additionally, the immunomodulatory role of sensory and sympathetic neurotransmitters is revised.
与关节疾病相关的慢性疼痛,如类风湿关节炎(RA)、骨关节炎(OA)和植入物无菌性松动(AL),是一种高度致残的症状,会影响受影响患者的活动能力和生活质量。神经免疫相互作用已被证明在慢性疼痛疾病的发生和确立中起着关键作用。免疫细胞释放细胞因子和免疫介质,通过与感觉神经末梢受体的相互作用,可以激活和敏化伤害感受器,引发疼痛。另一方面,感觉和交感神经纤维释放神经递质,与免疫细胞表面表达的特定受体结合,从而发挥免疫调节作用。巨噬细胞已被证明是神经免疫相互作用中的关键参与者。此外,巨噬细胞构成 RA、OA 和 AL 中占主导地位的免疫细胞群体。重要的是,针对巨噬细胞可以在慢性疼痛疾病中产生抗伤害感受作用。因此,本综述的目的是讨论这些关节疾病中炎症反应和神经纤维之间相互作用的性质和影响,以及它们在疼痛产生和维持中的作用。强调了巨噬细胞的作用。还描述了关节神经支配模式和炎症反应的改变。此外,还回顾了感觉和交感神经递质的免疫调节作用。
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