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Data and code from: Comparative transcriptomics reveals elevated TCL1A expression in human circulating immune cells across chronic pain conditions

Perez, Richard1; Tawfik, Vivianne1

Published May 26, 2026 on Dryad. https://doi.org/10.5061/dryad.37pvmcvz9

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May 26, 2026 version files 47.99 MB

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Abstract

Background

Chronic pain affects millions globally. The complex milieu of underlying risk factors and symptom heterogeneity, coupled with the absence of biomarkers, complicates management. Many studies examine pain through the lens of the human circulating immune system, as immune dysregulation is one potential contributor to pain. Typically, studies analyze both sexes together; however, there are known sex differences in the immune response to disease, with women at higher risk of autoimmunity. Similarly, chronic pain disproportionately affects women. Analyzing both men and women together and adjusting for sex may inadvertently remove sex-specific immune signatures associated with chronic pain, further hindering our understanding of its etiology.

Methods

To circumvent this, using transcriptomic meta-analysis, we reprocessed several bulk RNA-sequencing studies of human circulating immune cells across multiple chronic pain conditions to simultaneously examine both common and previously overlooked sex-specific transcriptomic signatures.

Results

Our meta-analysis encompassed bulk RNA-sequencing samples derived from human circulating immune cells from 142 chronic pain cases and 154 controls across six chronic pain conditions. When examining both sexes together, we identified 19 genes whose expression was altered in chronic pain. Notably, when examining women alone, we identified 34 altered genes, some with roles in autoimmunity, such as TCL1A. Further, we found that TCL1A expression significantly correlated with neuropathic symptom severity. Finally, this altered expression was confirmed at the protein level in women with neuropathic pain in a separate replication analysis.

Conclusion

Through transcriptomic meta-analysis of open-access data, we identified genes conserved across pain conditions and uncovered sex-specific signatures, including TCL1A, as a potential biomarker for neuropathic pain in women.