Can common differences in our genes explain why some people are more sensitive to pain than others?
| ISRCTN | ISRCTN16294731 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN16294731 |
| ClinicalTrials.gov (NCT) | Nil known |
| Clinical Trials Information System (CTIS) | Nil known |
| Protocol serial number | B3236 |
| Sponsor | University of Bristol |
| Funders | Above and Beyond, the University Hospitals Bristol Charity, via their Neurosciences and Mental Health Legacies Call. Grant reference ABL-2019-20-10, University of Bristol, Medical Research Council, Wellcome Trust, Cancer Research UK |
- Submission date
- 02/11/2021
- Registration date
- 25/11/2021
- Last edited
- 14/01/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Other
Plain English summary of protocol
Background and study aims
We know that genes influence our sensitivity to pain, but we do not have a full understanding of how this happens - which genes are important and why?
Who can participate?
We are recruiting participants from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort who have specific, common, changes in a gene heavily implicated in pain sensitivity call Transient Receptor Potential A1 (TRPA1).
What does the study involve?
We will invite participants to take part, based upon their known genetic information i.e. if they have or do not have these common changes in their TRPA1 gene. We will then carefully determine their pain sensitivity using quantitative sensory testing. This includes determining their heat and cold detection thresholds and pain thresholds, their mechanical detection thresholds, and their mechanical (punctate and pressure) pain thresholds. We will then apply 10% cinnamaldehyde, an activator of TRPA1, to their forearm for 20 minutes, measure any changes in blood flow and then repeat the sensory testing.
What are the possible benefits and risks of participating?
There are some risks associated with participating. Some pain will be experienced, though this will be minimized. The stimuli, particularly the cinnamaldehyde, may cause some redness of the skin which will settle on its own. Any sensations evoked by the cinnamaldehyde can be reduced by gently cooling the affected area.
Where is the study run from?
University of Bristol (UK)
When is the study starting and how long is it expected to run for?
November 2018 to January 2022
Who is funding the study?
Above and Beyond, the University Hospitals Bristol Charity, via their Neurosciences and Mental Health Legacies Call. Grant reference ABL-2019-20-10.
The UK Medical Research Council and Wellcome (Grant ref: 21765/Z/19/Z) and the University of Bristol provide core support for ALSPAC.
Individual team members are supported by the MRC (MC_UU_00011) and the University of Bristol, Wellcome Trust (202802/Z/16/Z) and Cancer Research UK (CRUK) Integrative Cancer Epidemiology Programme (C18281/A29019).
Who is the main contact?
Dr Jim Dunham, james.p.dunham@bristol.ac.uk
Contact information
Scientific
School of Physiology, Pharmacology and Neuroscience
Bristol Anaesthesia, Critical Care and Pain Research
Faculty of Biomedical Sciences
University of Bristol
Biomedical Sciences Building - E27
Tankard's Close
Bristol
BS8 1TD
United Kingdom
 ORCID ID |
0000-0002-1435-5043 |
|---|---|
| james.p.dunham@bristol.ac.uk |
Study information
| Primary study design | Observational |
|---|---|
| Study design | Single centre adaptive recall by genotype study |
| Secondary study design | An adaptive recall by genotype |
| Participant information sheet | 40614_PIS_v6_09Sep2019.pdf |
| Scientific title | Evaluating the association of TRPA1 gene polymorphisms with pain sensitivity: A protocol for an adaptive recall by genotype study. |
| Study objectives | Individuals homozygous for common (MAF>1%) SNPs in TRPA1 will have altered acute pain sensitivity as demonstrated by Quantitative Sensory Testing. |
| Ethics approval(s) | Approved 29/10/2019, ALSPAC Ethics and Law Committee (Children of the 90s, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK; +44 (0)117 331 0010; alspac-ethics@bristol.ac.uk), ref: 94082 |
| Health condition(s) or problem(s) studied | The association of TRPA1 gene polymorphisms with pain sensitivity |
| Intervention | Five TRPA1 SNPs known to introduce missense mutations and with minor allele frequencies of >1% hypothesized to impact TRPA1 function will be investigated. The effect of these five SNPs will be assessed in three groups due to the high linkage disequilibrium between two pairs of minor alleles. QST results from the individuals in these three test groups will be compared to those of a reference group who are homozygous for the major (ancestral) allele at all five SNPs. The results will be subject to planned interim assessments for futility to alter recruitment if there is low probability of success of detecting a phenotype for a given allele until a maximum of 100 participants have been assessed. Heat pain threshold is the primary outcome. The SNPs of interest were rs7819749, rs959976 with rs920829, rs16937976 with rs13268757 (dbSNP build 154, GRCh38) and a control group of individuals homozygous for all five major alleles. Investigators and participants will remain blind to genotype throughout the recruitment and data collection phases of the study. The participants will be assessed using quantitative sensory testing (QST) before and after sensitisation by topical application of 10% cinnamaldehyde (a known activator of TRPA1). QST paradigms are based upon the DFNS protocol, streamlined in line with the primary hypothesis to omit some non-nociceptive assessments. |
| Intervention type | Genetic |
| Primary outcome measure(s) |
Measured before and after 20 minute topical application of 10% cinnamaldehyde in ethanol: |
| Key secondary outcome measure(s) |
Measured before and after 20 minute topical application of 10% cinnamaldehyde in ethanol: |
| Completion date | 01/01/2022 |
Eligibility
| Participant type(s) | Other |
|---|---|
| Age group | Adult |
| Sex | All |
| Target sample size at registration | 100 |
| Key inclusion criteria | Participants within the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort who are a regionally representative cross-sectional population aged around 30 years (with a correspondingly relatively low incidence of chronic pain). |
| Key exclusion criteria | 1. Neurological disorders including peripheral neuropathy 2. Regular use of analgesics 3. Any pain medication taken within 24 hours of QST 4. Pregnancy 5. Acute or Chronic pain conditions 6. Severe anxiety/depression 7. Allergy to cinnamon, mustard, alcohol / chlorhexidine wipes, latex. 8. Use of non-prescribed or recreational drugs (assessed by questionnaire). |
| Date of first enrolment | 27/01/2020 |
| Date of final enrolment | 31/12/2021 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centre
Bristol
BS8 1TD
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| IPD sharing plan | The current data sharing plans for this study are unknown and will be available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | 12/01/2022 | 14/01/2022 | Yes | No | |
| Participant information sheet | version 6 | 09/09/2019 | 04/11/2021 | No | Yes |
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
| Protocol (preprint) | 01/12/2020 | 04/11/2021 | No | No |
Additional files
- 40614_PIS_v6_09Sep2019.pdf
- Participant information sheet
- 40614_Protocol-preprint_01Dec2020.pdf
- Protocol (preprint)
Editorial Notes
14/01/2022: Publication reference added.
26/11/2021: Internal review.
04/11/2021: Trial's existence confirmed by University of Bristol.
