Abstract

Background: Chronic musculoskeletal pain (CMP) disorders, including fibromyalgia, osteoarthritis, and chronic low back pain, are prevalent conditions that result in substantial disability, psychological distress, and reduced quality of life (QoL). Emerging evidence identifies central sensitization (CS), characterized by heightened responsiveness of the central nervous system to nociceptive stimuli, as a key mechanism in the persistence and amplification of pain. However, the broader biopsychosocial impact of CS in a single integrated framework remains underexplored. Objectives: This study aimed to investigate the relationship between central sensitization and disability, sleep disturbance, depression, and quality of life in individuals with CMP. Additionally, it assessed whether demographic factors age, sex, and pain duration moderate these relationships. Methods: A cross-sectional analysis was conducted on 150 participants aged 25–75 years with chronic musculoskeletal pain for ≥3 months. Participants completed the validated Gujarati versions of the Central Sensitization Inventory (CSI-G), RolandMorris Disability Questionnaire (RMDQ-G), Pittsburgh Sleep Quality Index (PSQI-G), Patient Health Questionnaire-9 (PHQ-9), and Short Form-12 (SF-12) for physical and mental QoL. Correlation and regression analyses were performed using SPSS v20.0, with moderation analyses evaluating the demographic influences. Results: Twenty percent of the participants exhibited clinically significant CS and were predominantly female. The CSI-G scores were significantly correlated with increased disability (ρ = 0.530), poor sleep quality (ρ = 0.363), higher depression (ρ = 0.656), and reduced QoL (SF-12 PCS: ρ = -0.467; MCS: ρ = -0.406) (all p < 0.001). Regression analysis identified depression, disability, sleep quality, pain duration, and sex as the significant predictors of CS. Age moderated the CS–disability link, while longer pain duration intensified the CS–depression association. Conclusion: Central sensitization is a major contributor to functional, psychological, and quality of life impairments in CMP.These findings emphasize the need for multidimensional personalized interventions targeting central mechanisms, particularly in females and patients with prolonged pain.Routine CS screening and integrated management strategies may improve the outcomes and enhance the overall well-being of the population.

• 1.   Roldán-Jiménez C, Pérez-Cruzado D, Neblett R, Gatchel R, Cuesta-Vargas A. Central Sensitization in Chronic Musculoskeletal Pain Disorders in Different Populations: A CrossSectional Study. Pain medicine. 2020.
• 2.   Yücel F, Toprak CS. Central sensitizationrelated symptoms and their relationship to disability in prevalent chronic musculoskeletal pain: A cross-sectional study. Musculoskeletal science & practice. 2024;73:103147.
• 3.   Nijs J, George S, Clauw D, Fernández de las Peñas C, Kosek E, Ickmans K, et al. Central sensitisation in chronic pain conditions: latest discoveries and their potential for precision medicine. The Lancet Rheumatology. 2021;3 5.
• 4.   Latremoliere A, Woolf CJ. Central Sensitization: A Generator of Pain Hypersensitivity by Central Neural Plasticity. The Journal of Pain. 2009;10(9):895-926.
• 5.   Mayer TG, Neblett R, Cohen H, Howard KJ, Choi YH, Williams MJ, et al. The Development and Psychometric Validation of the Central Sensitization Inventory. Pain Practice. 2012;12(4):276-85.
• 6.   Meeus M, Nijs J. Central sensitization: a biopsychosocial explanation for chronic widespread pain in patients with fibromyalgia and chronic fatigue syndrome. Clinical Rheumatology. 2006;26:465-73.
• 7.   Dionísio GH, Salermo VY, Padilha A. Central sensitization and beliefs among patients with chronic pain in a primary health care unit. Brazilian Journal Of Pain. 2020.
• 8.   Takeuchi T, Hashimoto K, Koyama A, Asakura K, Hashizume M. The Association of Central Sensitisation with Depression, Anxiety, and Somatic Symptoms: A Cross-Sectional Study of a Mental Health Outpatient Clinic in Japan. Life. 2024;14.
• 9.   Werneke M, Hart D, George S, Stratford P, Matheson J, Reyes A. Clinical outcomes for patients classified by fear-avoidance beliefs and centralization phenomenon. Archives of physical medicine and rehabilitation. 2009;90 5:768-77.
• 10.   Abeler K, Bergvik S, Sand T, Friborg O. Daily associations between sleep and pain in patients with chronic musculoskeletal pain. Journal of Sleep Research. 2021;30.
• 11.   Huber F, Toledo T, Newsom G, Rhudy J. The relationship between sleep quality and emotional modulation of spinal, supraspinal, and perceptual measures of pain. Biological Psychology. 2022;171.
• 12.   Friedman A, Regan K. A Deep Dive into the Relationship between Sleep Deprivation and Pain Perception: A Cross-Population Analysis. Research Posters. 2024.
• 13.   Miller L, Caño A. Comorbid chronic pain and depression: who is at risk? The journal of pain : official journal of the American Pain Society. 2009;10 6:619-27.
• 14.   Hooten W. Chronic Pain and Mental Health Disorders: Shared Neural Mechanisms, Epidemiology, and Treatment. Mayo Clinic proceedings. 2016;91 7:955-70.
• 15.   Maallo A, Moulton E, Sieberg C, Giddon D, Borsook D, Holmes S. A lateralized model of the pain-depression dyad. Neuroscience & Biobehavioral Reviews. 2021;127:876-83.
• 16.   Latremoliere A, Woolf C. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. The journal of pain: official journal of the American Pain Society. 2009;10 9:895-926.
• 17.   Bid D, Neela S, Rathod P, Ramalingam T. Content Validity and Test-Retest Reliability of the Gujarati Version of the Central Sensitization Inventory. NJIRM. 2016;7:18-24.
• 18.   Nambi G. Reliability, validity, sensitivity and specificity of Guajarati version of the RolandMorris Disability Questionnaire. Journal of back and musculoskeletal rehabilitation. 2013;26:149-53.
• 19.   Nariya D, Subhash K. Reliability and Validity of Gujarati Pittsburgh Sleep Quality Index: A Cross-sectional Study. Journal of Clinical and Diagnostic Research. 2021;15:YC04-YC7.
• 20.   Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. Journal of general internal medicine. 2001;16(9):606-13.
• 21.   Bais M, Thakrar G. Reliability and Validity of Gujarati Version of SF-12 in Geriatrics. International Journal of Science and Research (IJSR). 2022;11(1).
• 22.   Guekos A, Saxer J, Gallegos DS, Schweinhardt P. Differences in central sensitisation between healthy men and women in Switzerland: a single-centre trial. The Lancet Rheumatology. 2022.
• 23.   Barcelon E, Chung S, Lee J, Lee SJ. Sexual Dimorphism in the Mechanism of Pain Central Sensitization. Cells. 2023;12.
• 24.   Ross J, Queme L, Lamb J, Green K, Jankowski M. Sex differences in primary muscle afferent sensitization following ischemia and reperfusion injury. Biology of Sex Differences. 2018;9.
• 25.   Unruh A. Gender variations in clinical pain experience. Pain. 1996;65:123-67.
• 26.   Michael C, Barrett A. Gender Differences in Pain: Examining Explanations for the Association. Innovation in Aging. 2021;5:887-8.
• 27.   Goldoni ES, Bittencourt J, Santo LRDE, De Souza EB, De Faria JLR, De Andrade Alexandre DJ, et al. Neuropathic-like symptoms and central sensitization related signs and symptoms negatively affect the functional performance of patients with knee osteoarthritis–a crosssectional study. Osteoarthritis and Cartilage Open. 2023;5.
• 28.   Verbunt J, Seelen H, Vlaeyen J, Heijden G, Heuts P, Pons K, et al. Disuse and deconditioning in chronic low back pain: concepts and hypotheses on contributing mechanisms. European Journal of Pain. 2003;7.
• 29.   Crombez G, Vervaet L, Lysens R, Baeyens F, Eelen P. Avoidance and Confrontation of Painful, Back-Straining Movements in Chronic Back Pain Patients. Behavior Modification. 1998;22:62-77.
• 30.   Vandael K, Vervliet B, Peters M, Meulders A. Excessive generalization of pain-related avoidance behavior: mechanisms, targets for intervention, and future directions. Pain. 2023;164:2405-10.
• 31.   Sachau J, Kersebaum D, Hüllemann P, Adolf D, Kabelitz M, Keller T, et al. The association of self-reported symptoms of central sensitization and sleep disturbances in neuropathic pain. Pain Reports. 2023;8.
• 32.   Bento APDS, Filho N, Ferreira A, Cassetta AP, De Almeida RS. Sleep quality and polysomnographic changes in patients with chronic pain with and without central sensitization signs. Brazilian journal of physical therapy. 2023;27 3:100504.
• 33.   Aoyagi K, He J, Clauw D, Sharma N. Sleep quality in individuals with chronic low back pain and central sensitization. Physiotherapy research international: the journal for researchers and clinicians in physical therapy. 2022.
• 34.   Karimi R, Mallah N, Scherer R, Rodríguez-Cano R, Takkouche B. Sleep quality as a mediator of the relation between depression and chronic pain: a systematic review and meta-analysis. British journal of anaesthesia. 2023.
• 35.   Sun Y, Laksono I, Selvanathan J, Saripella A, Nagappa M, Pham C, et al. Prevalence of sleep disturbances in patients with chronic non-cancer pain: A systematic review and meta-analysis. Sleep medicine reviews. 2021;57:101467.
• 36.   Reid M, Hamilton K, Nilsson S, Owens M, Phillips J, Finan P, et al. Elevated pain sensitivity is associated with reduced REM sleep in females with comorbid temporomandibular disorder and insomnia. Pain medicine. 2024.
• 37.   Williams D. Phenotypic Features of Central Sensitization. Journal of applied biobehavioral research. 2018;23 2.
• 38.   Haack M, Engert L, Besedovsky L, Goldstein M, Devine J, Dang R, et al. Alterations of pain pathways by experimental sleep disturbances in humans: Central pain-inhibitory, cyclooxygenase, and endocannabinoid pathways. Sleep. 2023.
• 39.   Tafet G, Bernardini R. Psychoneuroendocrinological links between chronic stress and depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2003;27:893-903.
• 40.   Tafet G. P-1403 - the Link Between Chronic Stress and Depression at the Psychological and Neurobiological Interface. European Psychiatry. 2012;27:1.
• 41.   Ishak W, Wen R, Naghdechi L, Vanle B, Dang J, Knosp M, et al. Pain and Depression: A Systematic Review. Harvard Review of Psychiatry. 2018;26:352.
• 42.   Craner J, Flegge L, Lake E, Perra A. Patients with Clinically Elevated Depressive Symptoms Report Improvements in Mood, Pain, and Functioning following Participation in Interdisciplinary Pain Rehabilitation. Pain medicine. 2021.
• 43.   Li W, Liu P, Hu Y, Meng J. Pain Modulates Responses to Emotional Stimuli. Frontiers in Psychology. 2020;11.
• 44.   Scaini S, Davies S, De Francesco S, Pelucchi A, Rubino S, Battaglia M. Altered pain perception and nociceptive thresholds in major depression and anxiety disorders: A meta-analysis. Neuroscience & Biobehavioral Reviews. 2025;169.
• 45.   Zeng J, Liao Z, Lin A, Zou Y, Chen Y, Liu Z, et al. Poor control of pain increases the risk of depression: a cross-sectional study. Frontiers in Psychiatry. 2025;15.
• 46.   Ojeda B, Dueñas M, Salazar A, Micó J, Torres L, Failde I. Factors Influencing Cognitive Impairment in Neuropathic and Musculoskeletal Pain and Fibromyalgia. Pain Medicine. 2018;19:499.
• 47.   Coppieters I, Ickmans K, Cagnie B, Nijs J, De Pauw R, Noten S, et al. Cognitive Performance Is Related to Central Sensitization and Healthrelated Quality of Life in Patients with Chronic Whiplash-Associated Disorders and Fibromyalgia. Pain physician. 2015;18 3.
• 48.   Nimbi F, Renzi A, Mesce M, Limoncin E, Galli F. Central sensitization symptoms in vulvodynia: exploring the role of temperament, personality traits, childhood adverse events, defense mechanisms, and mental pain on quality of life. The journal of sexual medicine. 2024.
• 49.   Kieskamp S, Paap D, Carbo M, Wink F, Bos R, Bootsma H, et al. Central sensitization has major impact on quality of life in patients with axial spondyloarthritis. Seminars in arthritis and rheumatism. 2021;52:151933.

Data Sharing Statement

Funding