Neurophysiological and microbiome-associated factors influencing the outcomes of physical therapy in patients with chronic pain and depressive symptoms
DOI:
https://doi.org/10.32782/2077-6594/2026.2/24Keywords:
chronic pain, depressive symptoms, physical therapy, central sensitization, microbiome, gut-brain axis, psychoemotional factorsAbstract
Purpose: to assess the impact of neurophysiological and microbiome-associated factors on the outcomes of physical therapy in patients with chronic pain and depressive symptoms. Materials and methods. The study included 86 patients with chronic pain syndrome lasting more than 3 months and depressive symptoms. The study had an observational analytical prospective design with an assessment of indicators before and after a course of physical therapy. Adult patients of both sexes were involved. A structured questionnaire based on validated scales was used: VAS, BPI, PHQ-9, GAD-7, CSI, PCS, PSQI, PSS, IPAQ, TSK. Microbiome-associated factors were assessed indirectly (gastrointestinal symptoms, dietary habits, antibiotic use). Statistical analysis included correlation and multiple regression analysis; the level of statistical significance was set at p < 0.05. The study complied with the ethical principles of the Declaration of Helsinki. Results. After the course of physical therapy, a statistically significant decrease in pain intensity (by 38 %), a decrease in depressive symptoms and stress, and an improvement in sleep quality were observed. It was found that higher rates of central sensitization, pain catastrophizing, and depressive symptoms were associated with a less pronounced effect of therapy (r = -0.39 – -0.52; p < 0.05). In contrast, a higher level of physical activity and better sleep quality were associated with a more favorable response to treatment. An improvement in functional activity was also noted in all main indicators. Conclusions. The effectiveness of physical therapy in patients with chronic pain is determined by the complex interaction of neurophysiological, psychoemotional, and behavioral factors, as well as potential microbiome-associated characteristics. The results obtained substantiate the need for an individualized biopsychosocial approach and can be used to optimize physical therapy programs.
References
Aaron RV, Ravyts SG, Carnahan ND, Bhattiprolu K, Harte N, McCaulley CC, et al. Prevalence of Depression and Anxiety Among Adults With Chronic Pain. A Systematic Review and Meta-Analysis. JAMA Network Open. 2025;8(3):e250268. DOI: 10.1001/jamanetworkopen.2025.0268
Kovačević I, Pavić J, Filipović B, Vulinec SO, Ilić B, Petek D. Integrated Approach to Chronic Pain – The Role of Psychosocial Factors and Multidisciplinary Treatment: A Narrative Review. International Journal of Environmental Research and Public Health. 2024;21(9):1135. DOI: 10.3390/ijerph21091135
Özkan DU, Polat M. Does the predominance of central sensitization alter the effect of balneotherapy combined with conventional physical therapy in patients with chronic low back and knee pain? International Journal of Biometeorology. 2026;70(3):75. DOI: 10.1007/s00484-026-03157-w
Yao M, Qu Y, Zheng Y, Guo H. The effect of exercise on depression and gut microbiota: Possible mechanisms. Brain Research Bulletin. 2025;220:111130. DOI: 10.1016/j.brainresbull.2024.111130
Ren H, Cao B, Xu Q, Zhao R, Li H, Wei B. Role of microbiota in pain: From bench to bedside. iMetaOmics. 2025;2(1):e58. DOI: 10.1002/imo2.58
Hayes MHS, Patterson DG. Experimental development of the graphic rating method. Psychological Bulletin. 1921;18:98–99
Pilowsky I, Kaufman A. An experimental study of atypical phantom pain. The British Journal of Psychiatry. 1965;111(481):1185–1187. DOI: 10.1192/bjp.111.481.1185
Cleeland CS, Ryan KM. Pain assessment: Global use of the Brief Pain Inventory. Annals of the Academy of Medicine of Singapore. 1994;23(2):129–138. https://pubmed.ncbi.nlm.nih.gov/8080219/
Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. Journal of General Internal Medicine. 2001;16(9):606–613. DOI: 10.1046/j.1525-1497.2001.016009606.x
Spitzer RL, Kroenke K, Williams JB, Löwe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Archives of Internal Medicine. 2006;166(10):1092–1097. DOI: 10.1001/archinte.166.10.1092
Neblett R. The central sensitization inventory: A user’s manual. Journal of Applied Biobehavioral Research. 2018;23(2):e12123. DOI: 10.1111/jabr.12123
Sullivan M, Bishop S, Pivik J. The Pain Catastrophizing Scale: Development and validation. Psychological Assessment. 1995;7(4), 524–532. https://www.researchgate.net/publication/232599723_The_Pain_Catastrophizing_Scale_Development_and_validation DOI: 10.1037/1040–3590.7.4.524
Buysse DJ, Reynolds CF, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Research. 1989;28(2):193–213. DOI: 10.1016/0165-1781(89)90047-4
Cohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. Journal of Health and Social Behavior. 1983;24(4):385–396. DOI: 10.2307/2136404
IPAQ Core Group. Guidelines for data processing and analysis of IPAQ – short and long forms. 2005:1–15, https://drive.google.com/file/d/1gehdq1-04eSWfbxscwtzXa1MUlD8Mffa/view
Miller RP, Kori SH, Todd DD. The Tampa Scale a Measure of Kinisophobia. The Clinical Journal of Pain. 1991;7(1):51. DOI :10.1097/00002508-199103000-00053
Bingham SA, Welch AA, McTaggart A, Mulligan АА, Runswick SA, Luben R, et al. Nutritional methods in the European Prospective Investigation of Cancer in Norfolk. Public Health Nutrition. 2001;4(3):847–858. DOI: 10.1079/phn2000102
World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects. JAMA. 2013;310(20):2191–2194. DOI: 10.1001/jama.2013.281053
Engel GL. The need for a new medical model: a challenge for biomedicine. Science. 1977;196(4286):129–136. DOI: 10.1126/science.847460
Hladkykh FV, Liadova TI, Matvieienko MS, Komorovsky R, Smiyan S, Student V. Central Sensitization and Nociplastic Pain: Shared Mechanisms in Fibromyalgia, Osteoarthritis, and Inflammatory Arthritis. Journal of Pain Research. 2026;19:571311. DOI: 10.2147/JPR.S571311
González-de-la-Flor А, Bravo-Aguilar M, Almazán-Polo J, García-Pérez-de-Sevilla G, Martínez-Lozano P, Romero-Morales C. Exploring the Multifactorial Predictors of Pain in Chronic Musculoskeletal Pain: A Regression-Based Study. Journal of Pain Research. 2025;18:2081–2091. DOI: 10.2147/JPR.S500636
Glette M, Stiles TC, Jensen MP, Nilsen TIL, Borchgrevink PC, Landmark T. Impact of pain and catastrophizing on the long-term course of depression in the general population: the HUNT pain study. Pain. 2021;162(6):1650–1658. DOI: 10.1097/j.pain.0000000000002168
Simic K, Savic B, Knezevic NN. Pain Catastrophizing: How Far Have We Come. Neurology International. 2024;16(3):483–501. DOI: 10.3390/neurolint16030036
Sgourda S, Loulla M, Zisiopoulou E, Katsiou K, Nikolaidi S, Kyrosis I, et. al. Examination of the Relationship Between Pain Intensity, Pain Perceptions, and Kinesiophobia in Patients with Non-Specific Chronic Musculoskeletal Pain. Muscles. 2025;4(3):27. DOI: https://doi.org/10.3390/muscles4030027
Wlazło M, Szlacheta P, Grajek M, Staśkiewicz-Bartecka W, Rozmiarek M, Malchrowicz-Mośko E, et al. he Impact of Kinesiophobia on Physical Activity and Quality of Life in Patients with Chronic Diseases: A Systematic Literature Review. Applied Sciences. 2025;15(4):2086; DOI: https://doi.org/10.3390/app15042086
Fan Y, Pedersen O. Gut microbiota in human metabolic health and disease. Nature Reviews Microbiology. 2021;19(1):55–71. DOI: 10.1038/s41579-020-0433-9
Kumari R, Yadav Y, Misra R, Das U, Das Adhikari U, Malakar P, et al. Emerging frontiers of antibiotics use and their impacts on the human gut microbiome. Microbiological Research. 2022;263:127127. DOI: 10.1016/j.micres.2022.127127
Bhatt S, Kanoujia J, Mohana Lakshmi S, Patil CR, Gupta G, Chellappan DK, et al. Role of brain-gut-microbiota axis in depression: emerging the-rapeutic avenues. CNS & Neurological Disorders – Drug Targets. 2023;22(2):276–288. DOI: 10.2174/1871527321666220329140804
Fülling C, Dinan TG, Cryan JF. Gut Microbe to Brain Signaling: What Happens in Vagus…. Neuron. 2019;101(6):998–1002. DOI: 10.1016/j.neuron.2019.02.008.
Cao Y, Fan X, Zang T, Qiu T, Fang Q, Bai J, et al. Prenatal depression-associated gut microbiota induces depressive-like behaviors and hippocampal neuroinflammation in germ-free mice. ranslational Psychiatry. 2025;15(1):383. DOI: 10.1038/s41398-025-03606-x
Garvey M. The Association between Dysbiosis and Neurological Conditions Often Manifesting with Chronic Pain. Biomedicines. 2023;11(3):748. DOI: 10.3390/biomedicines11030748
Su Y, Xia Y. Gut microbiota dysbiosis and depression: Bidirectional interactions, mediating pathways, and microecological therapeutics. Current Research in Food Science. 2026;12:101372. DOI: 10.1016/j.crfs.2026.101372
