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Altered BDNF Methylation in Patients with Chronic Musculoskeletal Pain and High Biopsychosocial Complexity

Authors Paoloni-Giacobino A, Luthi F, Stenz L, Le Carré J, Vuistiner P, Léger B

Received 3 March 2020

Accepted for publication 7 May 2020

Published 2 June 2020 Volume 2020:13 Pages 1289—1296

DOI https://doi.org/10.2147/JPR.S251782

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Michael Schatman


Ariane Paoloni-Giacobino,1,* François Luthi,2– 4,* Ludwig Stenz,1 Joane Le Carré,2,5 Philippe Vuistiner,2,5 Bertrand Léger2,5

1Medicine Faculty, Department of Genetic Medicine and Development, Geneva University, Geneva, Switzerland; 2Institute for Research in Rehabilitation, Clinique romande de réadaptation, Sion, Switzerland; 3Department of Musculoskeletal Rehabilitation, Clinique romande de réadaptation, Sion, Switzerland; 4Department of Physical Medicine and Rehabilitation, Orthopaedic Hospital, Lausanne University Hospital, Lausanne, Switzerland; 5Department of Medical Research, Clinique romande de réadaptation, Sion, Switzerland

*These authors contributed equally to this work

Correspondence: Bertrand Léger Email bertrand.leger@crr-suva.ch

Purpose: The INTERMED instrument, which was developed to measure patient’s biopsychosocial (BPS) complexity, represents a powerful diagnostic and therapeutic tool. Epigenetic changes are the interface between signals from the environment and genetic modifications, affecting gene expression, in particular, by DNA methylation of CpG dinucleotides in promotor regions of the corresponding genes. The brain-derived neurotrophic factor (BDNF) gene plays a crucial role in the central sensitization (CS) of pain. In this study, we hypothesized that chronic pain modifies the methylation levels of the BDNF gene in a manner that is interconnected with the BPS status.
Patients and Methods: Fifty-eight chronic musculoskeletal pain patients (CMSP) were enrolled in the study. DNA was extracted from blood samples, the methylation levels of 13 CpG sites in the BDNF promoter were measured by pyrosequencing, and association studies with various patient parameters and the INTERMED scores were performed.
Results: Interestingly, a negative correlation (− 0.40) was found between the total INTERMED scores and the average CpG methylation values of the BDNF gene, but no correlation was observed with the severity of pain, degree of anxiety, depression, or kinesiophobia and catastrophism. Moreover, the association was independent of age, sex and level of comorbidities.
Conclusion: This result shows that CMSP, in association with its biopsychosocial context, epigenetically decreases the degree of methylation of the BDNF promoter and should therefore increase the level of BDNF transcription. It also suggests a role of the INTERMED tool to detect a relationship between the BPS complexity and the epigenetic control of a target gene. The possible upregulation of BDNF expression might be, at least in part, the signal for chronic pain-induced central sensitization (CS). This could partly explain why patients with a higher level of complexity feel more pain than those with lower complexity.

Keywords: chronic pain, biopsychosocial complexity, BPS, INTERMED, brain-derived neurotrophic factor, BDNF, DNA methylation

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