Exploring the role of the immune system in maladaptive pain sensitisation

探索免疫系统在适应不良疼痛敏化中的作用

• 批准号: 2891755
• 金额: --
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2891755
• 关键词: Exploring; role; immune; system; maladaptive

In a physiological setting, pain sensitisation is a protective mechanism that functions to prevent further tissue damageand promote healing. At a cellular level, this is characterised by an increased responsiveness of nociceptors, owed to adecrease in threshold for neuronal firing and/or increase in the scale of the response. However, in a pathological setting,inappropriate pain sensitisation is a key feature of many debilitating disorders, including rheumatoid arthritis (RA). As achronic inflammatory disease, the pain sensitisation in RA is accompanied by the recruitment and infiltration of bloodderived immune cells to the synovial membrane of joints, these include lymphocytes, macrophages and neutrophils. Atthe synovium these immune cells promote inflammation by releasing proinflammatory mediators such as interleukin (IL)-1B, IL-6 and tumour necrosis factor a. Recently, evidence has emerged to suggest interactions between the secretedproinflammatory proteins and receptors present on nociceptors, which may play a role in facilitating pain sensitisation.However, these intercellular interactions and underlying mechanisms are yet to be fully understood. Here, this projectaims to employ a combination of research methods, ranging from primary cell cultures to in vivo models and PCR tobehavioural experiments, to delineate the role of blood derived immune cells in the sensitisation of peripheralnociceptors.This may ultimately have implications for future therapeutics.

在生理环境中，疼痛敏化是一种保护机制，可防止进一步的组织损伤并促进愈合。在细胞水平上，其特征是伤害感受器的反应性增加，这是由于神经元放电阈值的降低和/或反应规模的增加。然而，在病理环境中，不适当的疼痛敏化是许多使人衰弱的疾病的一个关键特征，包括类风湿性关节炎（RA）。作为慢性炎症性疾病，RA 的疼痛敏化伴随着血源性免疫细胞的募集和浸润到关节滑膜，这些细胞包括淋巴细胞、巨噬细胞和中性粒细胞。在滑膜，这些免疫细胞通过释放白细胞介素 (IL)-1B、IL-6 和肿瘤坏死因子 a 等促炎介质来促进炎症。最近，有证据表明分泌的促炎蛋白和伤害感受器上的受体之间存在相互作用，这可能在促进疼痛敏化方面发挥作用。然而，这些细胞间相互作用和潜在机制尚未完全了解。在这里，该项目旨在采用从原代细胞培养到体内模型以及 PCR 到行为实验等研究方法的组合，来描述血液来源的免疫细胞在外周伤害感受器致敏中的作用。这最终可能会对未来的治疗产生影响。