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This work was supported mainly by the Instituto de Salud Carlos III (ISCIII), State Secretary of Research + Development + Innovation (R + D + I) and European Regional Development Fund (ERDF)/European Social Fund (ESF) (FIS grants PI23CIII/00012 and PI18/00287). The funding agencies had no role in study design, data collection and analysis, interpretation of results, manuscript preparation or the decision to submit this manuscript for publication.

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Role of Serum Brain-Derived Neurotrophic Factor as a Biomarker of Chronic Pain in Older Adults

Publicated to:EUROPEAN JOURNAL OF PAIN 29 (5): e70014- - 2025-05-01 29(5), DOI: 10.1002/ejp.70014

Authors: Ortola, R; Sotos-Prieto, M; Carballo, A; Cabello-Plan, S; Koni, Aida; Mustieles, V; Garcia-Segura, L M; Artalejo, A R; Rodriguez-Artalejo, F; Garcia-Esquinas, E

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Abstract

BackgroundSerum brain-derived neurotrophic factor (BDNF) has emerged as a promising biomarker for chronic pain (CP) research and treatment. Yet, most human studies have been limited by small sample sizes, inadequate control of confounders and a lack of focus on sex and mental health differences.MethodsThis study included data from 1932 community-dwelling individuals aged >= 65 years, randomly sampled from the Spanish general population. Serum BDNF was quantified by ELISA. CP characteristics were assessed using the European Chronic Pain Survey and classified according to electronic medical records (ICPC-2 codes). Linear regression models-adjusted for sociodemographic, lifestyle and clinical factors-and stratified analyses by sex and depression status (defined by Geriatric Depression Scale score, recent physician diagnosis or antidepressant use) were performed.ResultsAmong 962 men and 970 women, mean BDNF concentrations were 18.55 (5.66) ng/mL and 19.39 (5.77) ng/mL, respectively. Most participants reported pain in multiple locations (median 3 sites, interquartile range: 2-4). In 511 participants with CP, probable musculoskeletal pain was predominant (n = 446), followed by nociplastic (n = 71), neuropathic (n = 54), visceral (n = 51) and vascular pain (n = 22). Notably, in non-depressed participants (n = 1639), women with severe or interfering pain showed lower BDNF concentrations [beta coefficient (95% confidence interval) = -2.62 ng/mL (-5.03, -0.22) and -3.09 ng/mL (-4.71, -1.47), respectively] compared to those without CP-a pattern not seen in men. Conversely, among men with depression (n = 293), both severe [-5.12 g/mL (-9.26, -0.99)] and interfering [-4.95 g/mL (-8.29, -1.61)] pain were linked to lower BDNF, a trend absent in depressed women. Similar associations were observed in analyses of musculoskeletal and nociplastic pain subtypes.ConclusionsWhile serum BDNF is a promising biomarker for CP, its reliability for gauging pain severity depends on patient sex and depression status. These factors must be considered to enhance the accuracy and clinical relevance of BDNF in CP evaluation.SignificanceOur study is the first to reveal that the relationship between serum BDNF and chronic pain is distinctly modulated by sex and depression. This novel insight challenges one-size-fits-all biomarker approaches and paves the way for more personalised, precision-based strategies in chronic pain diagnosis and management.

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