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Updated: Aug 9, 2025
Author Spotlight: Methodologies and Advancements of Chronic Pain Management Research
Published on: January 5, 2024
Transient Receptor Potential Ankyrin 1 (TRPA1) Methylation and Chronic Pain: A Systematic Review
Fulvio Celsi1, Francesca Peri2, Julia Cavasin2
1Institute for Maternal and Child Health-IRCCS Burlo Garofolo, 34137 Trieste, Italy.
Insights
Epigenetic changes in the TRPA1 gene may be linked to chronic pain. This systematic review suggests hypermethylation might increase pain sensitivity, though more research is needed.
Area of Science:
- Neuroscience
- Genetics
- Epigenetics
Background:
- Chronic pain is a significant global health burden affecting all age groups.
- The molecular mechanisms underlying chronic pain remain incompletely understood.
- Epigenetic modifications, particularly DNA methylation, are increasingly recognized as potential contributors to pain.
Approach:
- A systematic review and meta-analysis were performed on six selected studies.
- Data were extracted from three major databases, involving initial screening of 431 articles.
- TRPA1 gene methylation patterns were analyzed in relation to chronic pain and pain sensitivity.
Key Points:
- Analysis of methylation levels between healthy and chronic pain groups showed no significant difference.
- A moderate correlation (0.35) was observed between TRPA1 methylation and pain sensation, but with high heterogeneity (I² = 97%).
- The variability highlights challenges in generalizing findings due to study differences.
Conclusions:
- Despite high variability, results suggest a potential link between TRPA1 hypermethylation and increased pain sensitivity.
- This association may be mediated by altered TRPA1 gene expression.
- Further research is warranted to elucidate the precise role of TRPA1 epigenetics in chronic pain mechanisms.
Background And Objective:
Chronic pain represents a major global health issue in terms of psycho-physiological, therapeutic, and economic burden, not limited to adults but also to the pediatric age. Despite its great impact, its molecular mechanisms have still not been completely unraveled. Focusing on the impact of epigenetics in the pain complex trait, we assessed the association between chronic pain and the methylation pattern of TRPA1, a key gene related to pain sensitivity.
Methods:
We conducted a systematic review retrieving articles from three different databases. After deduplication, 431 items were subjected to manual screening, and then 61 articles were selected and screened again. Of these, only six were maintained for meta-analysis and analyzed using specific R packages.
Results:
Six articles were divided into two groups (group 1: comparison of mean methylation levels between healthy subjects and patients with chronic pain; group 2: correlation between mean methylation levels and pain sensation). A non-significant mean difference was obtained from the analysis of group 1 with a value of 3.97 (95% C.I. -7.79; 15.73). Analysis of group 2 showed a high level of variability between studies (correlation = 0.35, 95% C.I. -0.12; 0.82) due to their heterogeneity (I2 = 97%, p < 0.01).
Conclusions:
Despite the high variability observed in the different studies analyzed, our results suggest that hypermethylation and increased pain sensitivity could be connected, possibly due to the variation of TRPA1 expression.
