B3236 - A Recall by Genotype Study to investigate the role of common TRPA1 variants in acute pain perception - 22/01/2019

B number: 
B3236
Principal applicant name: 
Jim Dunham | University of Bristol
Co-applicants: 
Prof. Tony Pickering, Prof. Nic Timpson
Title of project: 
A Recall by Genotype Study to investigate the role of common TRPA1 variants in acute pain perception.
Proposal summary: 

Why do some people suffer with long term pain after an accident or surgery whilst another person recovers without incident? We believe that part of the answer lies in the subtle differences in people's genes. We are interested in how these little differences can add up to make an individual more or less likely to suffer from pain. Unfortunately we don't know at the moment which gene differences are important. We plan to invite people, from the ALSPAC cohort, with known common variants in a specific gene that has been linked to pain detection (TRPA1), to come for testing of their sensitivity to mildly painful stimulation. If we find people who have differences in their pain sensitivity, we will invite them back for more detailed tests. In these detailed tests, we will record the activity in their nerves during mildly painful stimulation to see if a change in their nerve activity underlies their differences in pain sensitivity.

The mildly painful stimulation that we use is well tolerated by both patients and volunteers. Most of our tests look at pain "threshold" e.g. the transition from warm to hot. We therefore use the lowest temperature that causes pain to be perceived. We will also ask participants to rate how much pain they feel in response to a given stimulus. We believe that these tests are less painful then giving blood or a skin biopsy. The participant can stop the experiment at any time if it is too uncomfortable.

Impact of research: 
Academic impact: 1. Establish a pipeline / protocol to determine the influence of genes on acute and chronic pain. 2. Manuscripts a. Pain QST within a Recall by Genotype Paradigm. b. Human C fibre microneurography within a Recall by Genotype Paradigm. c. Demonstration of the utility of a human measure of nociceptor transduction. 3. Conference Presentations 4. Forging and Enhancing University of Bristol collaborations with other research institutions with international influence (including Oxford (U.K.), Northwestern and Washington (U.S.)). 5. Forging and Enhancing University of Bristol collaboration with industry (Lilly). 6. Forging and Enhancing interdisciplinary work within Bristol (Neurosciences with Genetic Epidemiology) and outside of Bristol (pharmaceutical industry - Lilly and US research institutions: Northwestern, Washington). Economic and societal impacts The ability to accurately risk assess members of the public and patients for their risk of enhanced acute and chronic pain will enable targeted provision of analgesia i.e. precision medicine. This has the potential to reduce unnecessary analgesic consumption (a critical need in the context of the epidemic of prescription opiate deaths) whilst also preventing pain in those most at risk. This improves quality of life for patients and promises improved economic contribution via reduction in time off work.
Date proposal received: 
Wednesday, 9 January, 2019
Date proposal approved: 
Thursday, 10 January, 2019
Keywords: 
Genetic epidemiology (including association studies and mendelian randomisation)