Fibromyalgia and refractory pain in rheumatic diseases

风湿性疾病中的纤维肌痛和顽固性疼痛

• 批准号: MR/W027585/1
• 负责人: David Andersson
• 金额: $ 81.67万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FW027585%2F1
• 关键词: Fibromyalgia; refractory; pain; rheumatic; diseases

Fibromyalgia is one of the most common causes of chronic pain worldwide. There is no diagnostic test available, and patients are diagnosed based on how severe and widespread their pain is and whether they have other symptoms, such as fatigue, sleep problems and depression. Treatment of fibromyalgia is focused on exercise and education, which help patients become more active and cope better with pain. Drugs that are used to treat pain in fibromyalgia are effective in some patients, but often cause problematic side effects and regularly become less effective with time. Fibromyalgia has a severe impact on quality of life, but the fact that patients look healthy can make it difficult for them to qualify for benefits and to convince their environment about how they feel. Although fibromyalgia affects more than 1 in 50 people, the cause of disease remains unknown. A better understanding of the cause of fibromyalgia, is likely to dramatically accelerate development of improved treatments and invention of diagnostic tests. We have discovered that the body's normal defence mechanism, the immune system, is responsible for pain in fibromyalgia patients. Immune cells produce proteins called antibodies, which would normally be used to help us destroy bacteria and other parasites, thereby helping us fight infections, and to become immune to them. Our results show that fibromyalgia patients make antibodies that attack their own bodies, rather than infections. These antibodies stimulate pain-sensing nerves throughout the body, making patients too sensitive to pressure, temperature and thereby experiencing unrelenting pain. In our pilot experiments, we have purified antibodies from fibromyalgia patients (without other health conditions) and healthy volunteers and injected these to mice. Remarkably, mice that were given patient antibodies developed similar symptoms to the patients that the antibodies were taken from, whereas antibodies from healthy volunteers were without effect. While about 2% of the general population (mostly women) suffer from fibromyalgia, around 25% of people rheumatic disease suffer from this difficult chronic pain condition. Rheumatic disease can often be well controlled by drugs, but fibromyalgia and the pain it causes throughout the body does typically not improve by treatment. During this project we will determine whether fibromyalgia in rheumatic patients is also caused by antibodies that cause pain. Our results are very likely to lead to development of the first simple diagnostic tests, and this will dramatically reduce the stressful period of time, often a couple of years that it currently takes for patients to be diagnosed. It is also very likely that our work will lead to improved treatment of fibromyalgia, and some of the possible treatments are already used in other conditions caused by antibodies that attack our own bodies.

纤维肌痛是全球慢性疼痛最常见的原因之一。目前还没有诊断测试，患者的诊断是基于他们的疼痛有多严重和广泛，以及他们是否有其他症状，如疲劳，睡眠问题和抑郁症。纤维肌痛的治疗重点是锻炼和教育，这有助于患者变得更加活跃，更好地科普疼痛。用于治疗纤维肌痛疼痛的药物对某些患者有效，但通常会导致有问题的副作用，并且随着时间的推移会变得不那么有效。纤维肌痛对生活质量有严重影响，但患者看起来健康的事实可能使他们难以获得福利并说服他们的环境了解他们的感受。虽然纤维肌痛影响超过50人中的1人，但疾病的原因仍然未知。更好地了解纤维肌痛的原因，可能会大大加快改进治疗方法的发展和诊断测试的发明。我们已经发现，身体的正常防御机制，免疫系统，是负责纤维肌痛患者的疼痛。免疫细胞产生称为抗体的蛋白质，通常用于帮助我们消灭细菌和其他寄生虫，从而帮助我们对抗感染，并对它们产生免疫力。我们的研究结果表明，纤维肌痛患者产生的抗体攻击自己的身体，而不是感染。这些抗体会刺激全身的痛觉神经，使患者对压力、温度过于敏感，从而体验到持续的疼痛。在我们的试点实验中，我们从纤维肌痛患者（没有其他健康状况）和健康志愿者中纯化了抗体，并将其注射到小鼠中。值得注意的是，给予患者抗体的小鼠出现了与抗体所取自的患者相似的症状，而来自健康志愿者的抗体则没有效果。虽然大约2%的普通人群（主要是女性）患有纤维肌痛，但大约25%的风湿性疾病患者患有这种困难的慢性疼痛。风湿性疾病通常可以通过药物得到很好的控制，但纤维肌痛及其引起的全身疼痛通常不会通过治疗得到改善。在这个项目中，我们将确定风湿病患者的纤维肌痛是否也是由引起疼痛的抗体引起的。我们的研究结果很可能会导致第一个简单的诊断测试的发展，这将大大减少压力的时间，通常需要几年的时间来诊断患者。我们的工作也很有可能改善纤维肌痛的治疗，并且一些可能的治疗方法已经用于由攻击我们自己身体的抗体引起的其他疾病。