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.
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).
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
Bohic M
(2023)
Mapping the neuroethological signatures of pain, analgesia, and recovery in mice.
in Neuron
De C Williams A
(2024)
A thematic synthesis of qualitative studies and surveys of the psychological experience of painful endometriosis
in BMC Women's Health
Jami S
(2023)
Pain-causing stinging nettle toxins target TMEM233 to modulate NaV1.7 function.
in Nature communications
Lischka A
(2023)
Genetic landscape of congenital insensitivity to pain and hereditary sensory and autonomic neuropathies.
in Brain : a journal of neurology
Middleton SJ
(2022)
Nav1.7 is required for normal C-low threshold mechanoreceptor function in humans and mice.
in Brain : a journal of neurology
Perez-Sanchez J
(2023)
A humanized chemogenetic system inhibits murine pain-related behavior and hyperactivity in human sensory neurons.
in Science translational medicine
Title | ADVANTAGE coloured logo |
Description | circular shapes in three colours, imagined from a colon cross section |
Type Of Art | Artwork |
Year Produced | 2023 |
Impact | We have a distinct logo for our letters and forms, and a colour scheme of three colours. |
Title | videos to help participants use the Sibel wearable device for 18h a dy |
Description | Video of how to put on and take off the wearable. Video of how to charge the wearable and download its daily data. |
Type Of Art | Film/Video/Animation |
Year Produced | 2023 |
Impact | Second version of videos has been recorded. Sibel will be using these videos for other of their users/customers (for no charge by us) |
Description | MICA ADVANTAGE visceral pain consortium: Advanced Discovery of Visceral Analgesics via Neuroimmune Targets and the Genetics of Extreme human phenotype |
Amount | £4,101,153 (GBP) |
Funding ID | MR/W002426/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 06/2021 |
End | 06/2025 |
Title | ADVANTAGE national visceral pain survey |
Description | An on-line survey of visceral pain sufferers, to record visceral pain and other pains, and to record severity and body location (and depth). So far 1004 participants. |
Type Of Material | Physiological assessment or outcome measure |
Year Produced | 2022 |
Provided To Others? | No |
Impact | So far the one outstanding result is the frequency of fibromyalgia as a co-morbidity with visceral pain. |
Title | Pain diary ofr viosceral pain for ADVANTAGE |
Description | An online always-accesible pain diary to record pain, location and type of pain on a regular basis, daily or more frequenctly. To be used in conjunction with other methods or recording pain/lack of pain in a chronological manner. |
Type Of Material | Physiological assessment or outcome measure |
Year Produced | 2022 |
Provided To Others? | No |
Impact | None as yet, as the study has onylyjust gained full approval to start recruiting. |
Description | AstraZeneca phd award to grant |
Organisation | AstraZeneca |
Country | United Kingdom |
Sector | Private |
PI Contribution | Providing new genetic mutation found in people with anomalies of visceral pain sensing |
Collaborator Contribution | Will fund research to determine biological proof of effect, or not, of the novel genetic fondings |
Impact | None yet |
Start Year | 2022 |
Description | Post doc funding |
Organisation | Eli Lilly & Company Ltd |
Country | United Kingdom |
Sector | Private |
PI Contribution | We are discovering visceral pain genetic drivers |
Collaborator Contribution | Funding and confidential gene expression data |
Impact | None yet |
Start Year | 2022 |
Description | collaboration between three APDP patient cohort consortia |
Organisation | University of Oxford |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | A three way collaboration to pool pain patients in order to seek the genetic drivers of psychological drivers and protectors of pain. |
Collaborator Contribution | 1000 high phenotyped patients and genetic analysis |
Impact | None yet, planned for in 3-4 y time. |
Start Year | 2021 |
Description | ADVANTAGE annual meeting 12/9/2022 |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Study participants or study members |
Results and Impact | Annual meeting of our award, held in Cambridge. To introduce everyone, and for them to meet, and clinicians to present. Our primary target for this first meeting was charities and participants. |
Year(s) Of Engagement Activity | 2022 |
Description | Pain Collaborative Network Conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | An online conference organised by Crohns and Colitis UK, but wit international participation. A number of speakers, including me, and expert panel discussion thereafter. |
Year(s) Of Engagement Activity | 2021 |