Immune-inflammatory pathways and clinical changes in fibromyalgia patients treated with Mindfulness-Based Stress Reduction (MBSR): A randomized, controlled clinical trial
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Fibromyalgia (FM) is a highly prevalent and disabling syndrome characterized by chronic widespread musculoskeletal pain and a broad range of cognitive and affective symptoms. Up to now, the pathogenesis of FM is unknown although a peripheral and central sensitization involving an imbalance on immune biomarkers appears to have a relevant role in its aetiology. The aim of this study was to extend previous clinical findings of Mindfulness-Based Stress Reduction (MBSR) to both its impact on clinical symptomatology and immune biomarkers (IL-6, CXCL8, IL-10 and hs-CRP), and also to explore the role of biomarkers as predictors of efficacy.Methods A total of 70 female patients with FM were randomly assigned to two treatment modalities, namely Treatment as Usual (TAU) plus MBSR (n = 35) or TAU alone (n = 35). This study is embedded within a larger RCT (n = 225) that includes three study arms (TAU; TAU plus MBSR; and TAU plus the psychoeducative intervention FibroQoL), and a 12-month follow-up (clinical trial registration: NCT02561416). Blood cytokine assays and clinical assessment were conducted at baseline and post-treatment. Treatment effects were analysed using linear mixed models with intention to treat and per protocol analyses. In order to evaluate the balance between pro- and anti-inflammatory pathways, ratios of pro-inflammatory IL-6, CXCL8 and hs-CRP with the anti-inflammatory cytokine IL-10 were calculated (i.e. IL-6/IL-10, CXCL8/IL10 and hs-CRP/IL-10).Results The results show that MBSR is an efficacious intervention to reduce clinical severity of patients with FM. MBSR also prevents the tendency of IL-10 to decrease as observed in the TAU group. Higher levels of baseline CXCL8 levels attenuate the beneficial effect of MBSR practice on clinical symptomatology, including pain, energy, stiffness or quality of sleep. Furthermore, higher baseline IL-6/IL-10 and CXCL8/IL-10 ratios were associated with less improvement in psychological inflexibility following MBSR treatment.Discussion Our results show that mindfulness training has clinical efficacy in patients with FM. The results suggest that MBSR has significant immune regulatory effects in FM patients, while immune-inflammatory pathways may in part predict the clinical efficacy of MBSR. These cytokines and chemokines may be adequate biomarkers to monitor responsivity to MBSR.
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In a recent study of persons with fibromyalgia participating in mindfulness-based stress reduction, a higher ratio of pro- vs. anti-inflammatory cytokines (IL-6/IL-10) was associated with less improvement in psychological inflexibility during treatment.
“In a recent study in which persons with fibromyalgia participated in treatment comprising mindfulness-based stress reduction (MBSR), a higher ratio of pro- vs. anti-inflammatory cytokines (IL-6/IL-10) was associated with less improvement in psychological inflexibility during treatment [29].”
From Baseline Pro-Inflammatory Cytokine Levels Moderate Psychological Inflexibility in Behavioral Treatment for Chronic Pain (2022) · cites this paper as [29]
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Self-citationResearch in Mindfulness Interventions for Patients With Fibromyalgia: A Critical Review
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“As to the studies excluded of the current analysis due to the lack of a control group (Kaplan et al., 1993; Sephton et al., 2007; Amutio et al., 2014, 2018; Cash et al., 2015; Andres-Rodriguez et al., 2019) it should be noted that they were also excluded because of other factors namely because in some of them the inte…”
BackgroundBallesio, A., Zagaria, A., Vacca, M., Pariante, C. M., & Lombardo, C. (2023) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2023.05.006 · Cited by 29 · see citing works
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“In addition, MBIs have been shown to be effective in modifying FM-related immune-inflammatory markers [13].”
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Myalgia in myositis and myopathies
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Mind-body therapy for treating fibromyalgia: a systematic review
Steen, J. P., Kannan, V., Zaidi, A., Cramer, H., & Ng, J. Y. (2024) · Pain Medicine · doi:10.1093/pm/pnae076 · Cited by 27 · see citing works
“These studies involved MBSR 43,55 and yoga.”
InfluentialDoedee, F., van den Houdt, S. C. M., Widdershoven, J. W. M. G., & Kupper, N. H. M. (2021) · General Hospital Psychiatry · doi:10.1016/j.genhosppsych.2021.07.001 · Cited by 18 · see citing works
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“For meta-analysis, eleven studies [14, 18, 19, 23, 25, 29, 39, 40, 42, 44, 52] only focused on three biomarkers among the patients met the inclusion criteria, so we calculated the mean differences.”
MethodPhysiopathology of fibromyalgia
Rodríguez, D. F. G., & Abud‐Mendoza, C. (2020) · Reumatología Clínica (English Edition) · doi:10.1016/j.reumae.2020.02.004 · Cited by 16 · see citing works
Can Yogic Breathing Techniques Like Simha Kriya and Isha Kriya Regulate COVID-19-Related Stress?
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Objective Diagnosis of Fibromyalgia Using Neuroretinal Evaluation and Artificial Intelligence
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“, in pain, fatigue, stiffness and quality of sleep) after an 8-week standardized mindfulness program in patients with FM (Andrés-Rodríguez et al., 2019).”
BackgroundMethodInfluentialSelf-citationWÅHLÉN, K., YAN, H., WELINDER, C., Ernberg, M. M., Kosek, E., MANNERKORPI, K., GERDLE, B., & Ghafouri, B. (2021) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000002790 · Cited by 14 · see citing works
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“On the other hand, central nervous system activity appears to modulate immune activity, but how cytokines induce central sensitization is still unclear [27,28].”
BackgroundThe Influence of Meditative Interventions on Immune Functioning: A Meta-Analysis
Oyler, D. L., Hulett, J. M., Pratscher, S. D., Price‐Blackshear, M. A., Murphy, E. A., & Bettencourt, B. A. (2023) · Mindfulness · doi:10.1007/s12671-023-02157-w · Cited by 11 · see citing works
Modulation of inflammatory response and pain by mind-body therapies as meditation
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Rhodes, A., Martin, S., Guarna, J., Vowles, K., & Allen, T. (2020) · Journal of Contextual Behavioral Science · doi:10.1016/j.jcbs.2020.07.009 · Cited by 10 · see citing works
Devigili, G., Stefano, G. D., Donadio, V. A., Frattale, I., Grazzi, L., Mantovani, E., Nolano, M., Provitera, V., Quitadamo, S. G., Tamburin, S., et al. (2025) · Neurological Sciences · doi:10.1007/s10072-025-08048-3 · Cited by 11 · see citing works
“…controlled trial that enrolled and randomized 156 patients, showed that ACT was statistically superior to both the recommended pharmacological treatment (RPT: pregabalin + duloxetine) and the waiting list immediately after treatment, and improvements were maintained after 6 months [36, 37].”
Aoufy, K. E., Pezzutto, A., Pollina, A., Rasero, L., Bambi, S., Bellando-Randone, S., Guiducci, S., Maddali‐Bongi, S., & Matucci‐Cerinic, M. (2023) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph20032512 · Cited by 9 · see citing works
Mindfulness as a Symptom Management Strategy for Fibromyalgia: An Integrative Review.
Gordon, S., Brown, R., Hogan, M., & Menzies, V. (2023) · Journal of Holistic Nursing · doi:10.1177/08980101221123833 · Cited by 8 · see citing works
“…suggest that in a disorder such as FM, in which some suggest the condition is attended by a chronic state of mild inflammation, a mind-body intervention such as mindfulness has potential to support symptom improvement, both non-biologically as well as biologically (Andrés-Rodríguez et al., 2019).”
BackgroundMethodResultInfluentialImpact of different treatments for chronic pain on cognitive function: A systematic review
Brennecke, A. B., Barreto, E. S. R., Lins-Kusterer, L., Azi, L. M. T. D. A., & Kraychete, D. C. (2025) · British Journal of Pain · doi:10.1177/20494637241311784 · Cited by 8 · see citing works
Medina, S., O’Daly, O., Howard, M. A., Feliu‐Soler, A., & Luciano, J. V. (2022) · Mindfulness · doi:10.1007/s12671-021-01806-2 · Cited by 8 · see citing works
Self-citationMunroe, M. E., Young, K. A., Guthridge, J. M., Kamen, D. L., Gilkeson, G. S., Weisman, M. H., ISHIMORI, M. L., Wallace, D. J., Karp, D. R., Harley, J. B., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.866181 · Cited by 8 · see citing works
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Are You Listening? Facilitation of the Auditory Blink Response in People with Fibromyalgia
Berryman, C. F., Wallwork, S. B., Heredia‐Rizo, A. M., Knight, E., Camfferman, D., Russek, L. N., & Moseley, G. L. (2021) · Journal of Pain · doi:10.1016/j.jpain.2021.03.141 · Cited by 7 · see citing works
Ciacchini, R., Conversano, C., Orrù, G., Scafuto, F., Sabbatini, S., Paroli, M., Miniati, M., Matiz, A., Gemignani, A., & Crescentini, C. (2024) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph21111507 · Cited by 7 · see citing works
“Similarly, patients with FM reported reduced stress levels, increased quality of life (QoL), and perceived well-being after MBSR participation [50,58,65–67].”
Ferrés, S., Serrat, M., Auer, W., Royuela-Colomer, E., Almirall, M., Lizama-Lefno, A., Nijs, J., Maes, M. H. J., Luciano, J. V., Borràs, X., et al. (2024) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2024.12.149 · Cited by 7 · see citing works
Self-citationUtilization of Mind–Body Intervention for Integrative Health Care of COVID-19 Patients and Survivors
Yang, H., Setou, N., & Koh, E. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph19116618 · Cited by 7 · see citing works
“[70] RCT Spain Patients with fibromyalgia 70 (35 for each group) 100% Female 53 MBSR TAU 8 weeks • 2 h group session/week.”
BackgroundKarshikoff, B., Åström, J., Holmström, L., Lekander, M., Kemani, M. K., & Wicksell, R. K. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11092285 · Cited by 6 · see citing works
“, [5,7,8,29], and the effects of behavioral treatment on levels of inflammation [30], but few studies have evaluated the effect of inflammation on behavioral treatment for pain [25,29].”
BackgroundHuang, X., Lv, J., Zhu, D., Peng, H., & Yu, T. (2025) · Biogerontology · doi:10.1007/s10522-025-10287-y · Cited by 6 · see citing works
“…2010; Tomfohr et al. 2015; Torelly et al. 2022; Zgierska et al. 2008); 42 studies reported CRP, including 36 RCTs (Alhawatmeh et al. 2024, 2022; Andrés-Rodríguez et al. 2019; Barrett 2012; Bower et al. 2015; Chacko et al. 2016; Cohen et al. 2021; Creswell et al. 2012; Daubenmier et al. 2016;…”
Victorson, D. E., Morgan, T. M., Kutikov, A., Novakovic, K. R., KUNDU, S. D., Horowitz, B., Jackson, K., Addington, E. L., Murphy, K. M., Sauer, C., et al. (2022) · Contemporary Clinical Trials · doi:10.1016/j.cct.2022.107059 · Cited by 7 · see citing works
Behavioral Changes and Long-Term Cortical Thickness Alterations in Women with Fibromyalgia
Neto, P. G. D. O., Ramos, L. R., & DosSantos, M. F. H. (2024) · Journal of Manipulative and Physiological Therapeutics · doi:10.1016/j.jmpt.2024.08.018 · Cited by 5 · see citing works
How Can Experimental Endotoxemia Contribute to Our Understanding of Pain? A Narrative Review
Benson, S., & Karshikoff, B. (2023) · NeuroImmunoModulation · doi:10.1159/000534467 · Cited by 6 · see citing works
Gasión, V., Barceló‐Soler, A., Beltrán-Ruiz, M., Hijar-Aguinaga, R., Camarero-Grados, L., del Hoyo, Y. L., García‐Campayo, J., & Montero‐Marín, J. (2023) · BMC Complementary Medicine and Therapies · doi:10.1186/s12906-023-04240-0 · Cited by 5 · see citing works
“Amygdala and insula retraining (AIR) techniques were initially developed for CFS patients as a method to reduce the chronic over-sensitization and heightened fear response of the amygdala, which may underlie certain symptoms associated with both CFS and fibromyalgia [14–16].”
MethodJosefsson, D., Danielsson, L., & Jakobsson, M. (2026) · Frontiers in Pain Research · doi:10.3389/fpain.2026.1755744 · Cited by 3 · see citing works
Rometsch, C., Martin, A., & Cosci, F. (2025) · Clinical Psychology & Psychotherapy · doi:10.1002/cpp.70075 · Cited by 3 · see citing works
“Four studies investigated CFS including patients with an average age from 37 (Heins et al. 2010) (about two-thirds were females) to 49.5 years (Andrés-Rodríguez et al. 2019).”
InfluentialKwon, C., Lee, B., Chung, S.-Y., & Kim, J. W. (2020) · EXPLORE · doi:10.1016/j.explore.2020.05.016 · Cited by 3 · see citing works
Chokprasit, P., Yimthiang, S., & Veerasakul, S. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e20664 · Cited by 2 · see citing works
“The imbalance of pro-inflammatory and anti-inflammatory cytokines in the body can cause mild, ongoing inflammation in the central and peripheral nervous systems [20].”
Canella, R., Fazia, T., & Gardi, C. (2025) · Psychology Health & Medicine · doi:10.1080/13548506.2025.2561740 · Cited by 2 · see citing works
Mindfulness-based stress reduction for fibromyalgia: A step closer to precision psychiatry?
Carvalho, A. F., Fernandes, B. S., & Brunoni, A. R. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.06.020 · Cited by 2 · see citing works
Park, R., Mohiuddin, M., Poulin, P. A., Salomons, T. V., Edwards, R. R., Nathan, H., Haley, C., & Gilron, I. (2020) · PAIN Reports · doi:10.1097/pr9.0000000000000868 · Cited by 2 · see citing works
“A trial by AndrésRodrı́guez et al.(2) that investigated MBSR for fibromyalgia reported that of 66 participants, 34.”
MethodInfluentialKing, C. D., Boggero, I. A., Schulert, G. S., Pickerill, H. M., & Cole, S. W. (2021) · PAIN Reports · doi:10.1097/pr9.0000000000000874 · Cited by 2 · see citing works
Bases biológicas del mindfulness y su aplicación en la práctica clínica
Gómez, S. M., Peñaloza, M. J., Rodríguez, N. B., & Alba, L. H. (2022) · Universitas Médica · doi:10.11144/javeriana.umed63-2.mind · Cited by 2 · see citing works
Mindfulness-Based Interventions for Psychiatry
Ivkovic, A., Evans, S., Mirsky, P., Ashar, Y. K., & Muskin, P. R. (2024) · Tasman’s Psychiatry · doi:10.1007/978-3-030-51366-5_159 · Cited by 1 · see citing works
Neuroimmune interactions in musculoskeletal conditions. An introduction for clinicians
Schipholt, I. J. L., Coppieters, M. W., Scholten-Peeters, G. G. M., Hutchinson, M. R., & Klyne, D. M. (2025) · Musculoskeletal Science and Practice · doi:10.1016/j.msksp.2025.103469 · Cited by 1 · see citing works
Microbiome-derived metabolites alleviate chronic pain in a reserpine-induced model of fibromyalgia
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“Previous studies in fibro-myalgia patients have reported varying levels of systemic IL-10 9,44,46,49 while our study shows similar expression of IL-10 in both DRG and spinal cord in control and R-iFM states on a con-trol diet, with a significant increase in both groups on GMAD (Figure S1B).”
Chronic pain, fibromyalgia, and long COVID
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“Through the perceiving emotions, thoughts and feelings and integrating them into life, the encephalic region in the left cerebral prefrontal lobe can be enhanced and activated, so that patients can remain calm and goodhumored in the face of stress, thereby effectively reducing negative emotions [14].”
BackgroundEmotional Stress Relief Mechanism of English Translation Practitioners Based on Role Cognition
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A INTELIGÊNCIA ARTIFICIAL E SUAS IMPLICAÇÕES NO CAMPO DA GENÉTICA
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OBESIDADE MONOGÊNICA NÃO SINDRÔMICA: DOS GENES À TERAPIA
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Genética: Molecular, humana e médica 3
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A Psychological Approach to Functional Illness
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“The transformative approach to sex therapy aims to understand the psychological, biological, pharmacological, rational, and behavioral aspects of sexual issues [11].”
BackgroundInterdisciplinary Pain Treatment
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“111,112 Previous reviews have suggested that CBT may reduce PC among individuals with various chronic musculoskeletal disorders.”
Complementary and integrative medicine and women’s health
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“This pro fi le is consistent with previous evidence indicating alterations in cytokine production and immune dysfunction as relevant components of the disease pathophysiology (Andrés-Rodríguez et al., 2019; O ’ Mahony et al., 2021; Niu et al., 2025).”
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Gusmão, C. T. P., Özen, B., Neves, M. S. S. E., Scaini, G., Quevedo, J., Lussati, P. L., Aguiar, M. D. R. D. S., Calixto, C. T. D. S., António, A. A., Miguel, H. J. D., et al. (2026) · Anesthesia Research · doi:10.3390/anesthres3030027
- Authors
- Andrés-Rodríguez, L., Borràs, X., Feliu-Soler, A., Pérez-Aranda, A., Rozadilla-Sacanell, A., Montero-Marin, J., Maes, M., & Luciano, J. V.
- Affiliations
- Universitat Autònoma de Barcelona (ES)
- Chulalongkorn University (TH)
- Red de Investigación en Actividades Preventivas y Promoción de la Salud (ES)
- Corresponding author
- Luciano, Juan V.
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2019-08
- Volume
- 80
- Pages
- 109-119
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W2916592505
- Cited by
- 87
- References
- 74
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 7 · 2023: 18 · 2022: 16 · 2021: 9 · 2020: 14 · 2019: 3
- FWCI
- 8.36
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- BiblioBoard Library Catalog (Open Research Library) (submittedVersion, cc-by-nc-nd)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Fibromyalgia and Chronic Fatigue Syndrome Research
- Social Sciences › Psychology › Clinical Psychology › Mindfulness and Compassion Interventions
- Health Sciences › Medicine › Psychiatry and Mental health › Psychosomatic Disorders and Their Treatments
- Keywords
- fibromyalgia, mindfulness-based stress reduction, immune-inflammatory pathways, cytokines, interleukin-6, interleukin-8, IL-10, high-sensitivity C-reactive protein, IL-6/IL-10 ratio, psychological inflexibility, treatment response biomarkers, chronic widespread pain, sleep quality
- MeSH terms
- Adult, C-Reactive Protein, Female, Fibromyalgia, Humans, Middle Aged, Stress, Psychological, Biomarkers, Interleukin-6, Cytokines, Interleukin-8, Interleukin-10, Treatment Outcome, Meditation, Mindfulness
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