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

Lead Research Organisation: University of Cambridge
Department Name: Cambridge Institute for Medical Research

Abstract

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.

Technical Summary

The core purpose of the ADVANTAGE consortium is to enable better treatment for people with severe visceral pain. We will achieve this through three linked endeavours.

1) The establishment of a National Visceral Pain Resource (NVPR) of patients, by assembling expertly curated cohorts of individuals with severe visceral pain arising as a result of painful bladder syndrome, vaginal MESH surgery, endometriosis, inflammatory bowel disease (Crohn's & ulcerative colitis), autosomal dominant polycystic kidney disease or pancreatitis. We will also recruit individuals with lack of expected visceral pain. Each cohort will undergo extensive clinical, psychological and pain phenotyping (including app-based/wearable sensor technologies).

2) Analysis of our NVPR clinical and psychological data will allow sophisticated definitions and classifications of visceral pain types to identify drivers of severity and resilience to visceral pain. We will also probe for genomic and mitochondrial genomic variants and sex specific differences.

3) Our clinical research will be informed by mechanistic studies in mouse. Analysis of human serum samples in mouse models will allow us to test whether auto-antibodies contribute to visceral disease/pain states. Equally, we will define the molecular identity of sensory neurons innervating visceral organs allowing us to fine-tune our human results on gene or sex differences.

Our translational and interdisciplinary approach, uniting patient experts, clinical and pre-clinical pain researchers, visceral disease experts, psychologists, engineers and industrial collaborators will allow us to maximise the development of novel study tools, drugs and treatments - specifically tailored for visceral pain.

Our platform will be an open resource - designed to encourage data sharing, access to cohorts and links to other relevant clinical databases and platforms (see e.g. p. 2 and p. 12 of our Case for Support).

Publications

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