MICA ADVANTAGE visceral pain consortium: Advanced Discovery of Visceral Analgesics via Neuroimmune Targets and the Genetics of Extreme human phenotype

MICA ADVANTAGE 内脏疼痛联盟：通过神经免疫靶点和人类极端表型遗传学对内脏镇痛药的高级发现

• 批准号: MR/W002426/1
• 负责人: Geoff Woods
• 金额: $ 522.57万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 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=MR%2FW002426%2F1
• 关键词: MICA; ADVANTAGE; visceral; pain; consortium

The ADVANTAGE consortium aims to improve how we treat people with visceral diseases, such as endometriosis, colitis and kidney disease, focusing on their pain rather than just their underlying disease. One in twenty individuals in the UK are disabled by visceral pain - approximately as many people as live in the entire country of Wales. The condition is a terrible burden for those who suffer from it: causing pain not only during the most intimate moments of their lives, but also frequently triggering unpredictable episodes of pain "flares" that can need hospital admission. It is therefore surprising and disappointing how little we know about visceral pain; no one has systematically studied how the pain connects to the underlying visceral disease, how it relates to other health problems, and how it affects people's psychological wellbeing. Our consortium will set up a UK-wide database of visceral pain patients to address these questions. We will also study those nerves connecting inner organs to the brain to ultimately cause pain, as their exact identity is unknown. The database and biological knowledge collected will enable us to:1) answer why people with the same visceral disease can have completely different pain experiences, including flares; 2) start looking for painkillers and therapies specifically designed for visceral pain, which although they are desperately needed do not currently exist.Our work will be divided into various taskforces, each led by an internationally recognised expert clinician or scientist. All research will be enriched by input from patient and patient support organisations from start to finish. Our visceral pain database will enrol individuals with pain originating from the bladder, gut, lung, kidney, pancreas, uterus and vagina, and in the pelvis. It will be built on existing hospital and GP records and will be future-proof, set up to grow and recall volunteers for additional studies. We will also work closely with similar pain consortia being set up across the UK. We will look especially for people at the extremes: those with little pain despite clear disease, and those with severe pain despite few signs of disease. We will record their pain using standard self-report methods, but also explore other ways to capture their experience; for example, using automatic sensors to record activity and physiological changes throughout the day. To find out what causes severe pain in some people, we will study the genetic and immune systems of participants. We will also examine differences between men and women, why certain conditions predominantly affect women, and the under-representation of women in some research areas, to make sure that any new treatments benefit everyone equally. Our ultimate aim is to improve our understanding of visceral pain from the perspective of people living with the condition, so that the NHS can develop and offer patients more effective interventions and support to address the diverse nature of their symptoms and help improve their quality of life.

ADVANTAGE 联盟旨在改善我们治疗子宫内膜异位症、结肠炎和肾脏疾病等内脏疾病患者的方式，重点关注他们的疼痛，而不仅仅是他们的潜在疾病。在英国，二十分之一的人因内脏疼痛而致残——大约相当于整个威尔士的人口数量。这种情况对于患者来说是一个可怕的负担：不仅在他们生命中最亲密的时刻造成疼痛，而且经常引发不可预测的疼痛“发作”，可能需要住院治疗。因此，我们对内脏疼痛知之甚少，这既令人惊讶又令人失望。没有人系统地研究疼痛如何与潜在的内脏疾病相关，如何与其他健康问题相关，以及如何影响人们的心理健康。我们的联盟将建立一个全英国内脏疼痛患者数据库来解决这些问题。我们还将研究那些连接内部器官和大脑并最终引起疼痛的神经，因为它们的确切身份尚不清楚。收集的数据库和生物学知识将使我们能够：1）回答为什么患有相同内脏疾病的人可以有完全不同的疼痛体验，包括疼痛； 2) 开始寻找专门针对内脏疼痛设计的止痛药和疗法，尽管目前迫切需要这些药物和疗法，但目前还不存在。我们的工作将分为不同的工作组，每个工作组均由国际公认的专家临床医生或科学家领导。所有研究自始至终都将因患者和患者支持组织的投入而丰富。我们的内脏疼痛数据库将招募患有膀胱、肠道、肺、肾、胰腺、子宫和阴道以及骨盆疼痛的个体。它将建立在现有的医院和全科医生记录的基础上，并且不会过时，旨在培养和召回志愿者进行进一步的研究。我们还将与英国各地建立的类似疼痛联盟密切合作。我们将特别寻找极端的人：那些尽管有明显疾病但疼痛很少的人，以及那些尽管几乎没有疾病迹象但疼痛剧烈的人。我们将使用标准的自我报告方法记录他们的痛苦，但也会探索其他方法来捕捉他们的经历；例如，使用自动传感器记录全天的活动和生理变化。为了找出导致某些人剧烈疼痛的原因，我们将研究参与者的遗传和免疫系统。我们还将研究男性和女性之间的差异，为什么某些情况主要影响女性，以及女性在某些研究领域的代表性不足，以确保任何新疗法都能平等地惠及每个人。我们的最终目标是从患者的角度提高我们对内脏疼痛的理解，以便 NHS 能够制定并向患者提供更有效的干预措施和支持，以解决他们症状的多样性，并帮助改善他们的生活质量。

项目成果

Quantification of Digital Body Maps for Pain: Development and Application of an Algorithm for Generating Pain Frequency Maps

疼痛数字身体图的量化：生成疼痛频率图的算法的开发和应用

• DOI: 10.17863/cam.86862
• 发表时间: 2022
• 作者: Dixit A

Genetic landscape of congenital insensitivity to pain and hereditary sensory and autonomic neuropathies.

• DOI: 10.1093/brain/awad328
• 发表时间: 2023-12-01
• 期刊: Brain : a journal of neurology

A humanized chemogenetic system inhibits murine pain-related behavior and hyperactivity in human sensory neurons.

• DOI: 10.1126/scitranslmed.adh3839
• 发表时间: 2023-10-04
• 期刊: Science translational medicine
• 影响因子: 17.1
• 作者: Perez-Sanchez J;Middleton SJ;Pattison LA;Hilton H;Ali Awadelkareem M;Zuberi SR;Renke MB;Hu H;Yang X;Clark AJ;St John Smith E;Bennett DL
• 通讯作者: Bennett DL

Nav1.7 is required for normal C-low threshold mechanoreceptor function in humans and mice.

• DOI: 10.1093/brain/awab482
• 发表时间: 2022-10-21
• 期刊: Brain : a journal of neurology