Clinical Impact of Stage-Specific Central Sensitization-Related Symptoms in Hip Osteoarthritis

Clinical Impact of Stage-Specific Central Sensitization-Related Symptoms in Hip Osteoarthritis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Clinical Impact of Stage-Specific Central Sensitization-Related Symptoms in Hip Osteoarthritis Yoshihisa Ohashi, Kensuke Fukushima, Stephen K. Aoki, Kentaro Uchida, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7986921/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Purpose This study aimed to compare the characteristics of central sensitization (CS)-related symptoms between mild and severe hip osteoarthritis (OA) and to clarify their associations with hip pain. Methods A total of 116 patients with unilateral hip OA secondary to acetabular dysplasia or borderline dysplasia (center-edge angle ≤ 25°) were enrolled. Patients were classified into mild (Tönnis grade 0–1, n = 39) and severe (Tönnis grade 2–3, n = 77) OA groups. CS-related symptoms were assessed using the Central Sensitization Inventory (CSI), including domain-specific scores (Physical Symptoms, Emotional Distress, Headache/Jaw Symptoms, and Urological Symptoms). Hip pain intensity was evaluated with the Visual Analog Scale (VAS). Between-group comparisons were conducted, and multivariate regression analyses were performed to examine the associations between CSI domain scores and VAS. Results VAS scores were higher in the severe OA group than in the mild OA group. Total CSI scores did not differ significantly between groups. However, the Headache/Jaw Symptoms domain score was significantly higher in the mild OA group (p < 0.001) and was the only domain independently associated with hip pain intensity in this group (β = 0.59, p = 0.034). No significant associations were observed in the severe OA group. Conclusion CS-related symptoms, particularly headache and jaw complaints, play an important role in pain perception in mild hip OA. Evaluating and managing these symptoms may help optimize stage-specific pain treatment strategies for patients with hip OA. Health sciences/Diseases Health sciences/Health care Health sciences/Medical research Health sciences/Rheumatology Health sciences/Signs and symptoms Hip osteoarthritis Central sensitization Headache Temporomandibular disorders Hip pain Figures Figure 1 Figure 2 Introduction Hip osteoarthritis (OA) is a progressive joint disease that not only causes chronic pain but is also frequently accompanied by various physical symptoms and/or emotional distress [ 1 , 2 ]. These factors can influence pain severity and substantially reduce quality of life. Such complex symptomatology cannot be fully explained by structural joint damage alone [ 3 , 4 ], suggesting that additional mechanisms contribute to the overall disease burden in hip OA. Central sensitization (CS) refers to an amplification of pain signaling within the central nervous system and is considered to play an important role not only in chronic pain but also in a range of clinical symptoms in musculoskeletal disorders, including hip OA [ 5 – 7 ]. The Central Sensitization Inventory (CSI), a patient-reported outcome measure, enables the assessment of diverse CS-related symptoms [ 8 ]. Previous studies have reported associations between CSI scores, hip pain severity, and poor postoperative outcomes in patients with hip OA across different disease stages [ 9 – 12 ]. However, differences in the characteristics of CS-related symptoms across disease stages of hip OA have not yet been fully elucidated. Understanding the stage-specific features of CS-related symptoms and their relationships with hip pain is crucial for developing tailored treatment strategies for patients with hip OA. Thus, the aim of this study was to compare the characteristics of CS-related symptoms mild and severe stages of hip OA and to clarify their associations with pain, using the CSI. Methods Participants This study was approved by our Institutional Review Board, and all patients provided informed consent. The study was conducted in accordance with the Declaration of Helsinki. We enrolled 180 consecutive patients with hip OA scheduled to undergo unilateral hip arthroscopy, periacetabular osteotomy, or total hip arthroplasty (THA). To minimize heterogeneity in disease etiology, we included patients with unilateral hip OA secondary to acetabular dysplasia (AD) or borderline AD, defined by a center-edge (CE) angle of ≤ 25° [ 13 ]. Exclusion criteria included bilateral hip OA, previous hip surgery, and a history of rheumatologic disease. Consequently, we excluded 37 patients with bilateral hip OA, 17 patients with a CE angle > 25°, 5 patients with a history of previous surgery on the affected hip, and 5 patients with rheumatoid arthritis. This resulted in a final cohort of 116 participants. Hip OA severity was assessed radiographically using the Tönnis classification system [ 14 ]. Based on this system, 39 patients with Tönnis grade 0 or 1 were classified into the mild OA group, while 77 patients with Tönnis grade 2 or 3 were assigned to the severe OA group. Clinical Assessments The CSI consists of 25 self-reported items evaluating CS-related symptoms, each rated on a 5-point Likert scale (0 = never, 1 = rarely, 2 = sometimes, 3 = often, 4 = always) [ 8 ]. The total CSI score ranges from 0 to 100, with higher scores indicating greater symptom severity. The CSI is categorized into four symptom domains: Physical Symptoms (8 items: Q1, Q2, Q8, Q9, Q12, Q17, Q18, Q23), Emotional Distress (6 items: Q3, Q6, Q13, Q15, Q16, Q24), Headache/Jaw Symptoms (5 items: Q4, Q7, Q10, Q19, Q20), and Urological Symptoms (3 items: Q11, Q21, Q25) [ 8 ]. In this study, CSI scores were analyzed by domain, with participants independently completing the validated CSI Japanese version [ 15 ]. Domain-specific and total CSI scores were compared between the mild OA and severe OA groups. Hip pain intensity was assessed using the Visual Analog Scale (VAS). Associations between hip pain intensity and domain-specific CSI scores were evaluated within each group. The CSI score and VAS score assessments were conducted one month preoperatively. Statistical Analysis Results are expressed as means ± standard errors of the mean unless otherwise indicated. Patient demographics, VAS scores, total CSI scores, and domain-specific CSI scores were compared between the mild OA group and the severe OA group. The normality of continuous variables was assessed using the Shapiro-Wilk test. Since the data were not normally distributed, the Mann-Whitney U test was used for continuous variables, while the χ² test was applied for categorical variables. Multivariate regression analyses were conducted to identify factors influencing VAS scores. This analysis was performed separately for the mild OA group and the severe OA group. The four CSI domains (Physical Symptoms, Emotional Distress, Headache/Jaw Symptoms, and Urological Symptoms) were used as explanatory variables, with VAS score as the dependent variable. The models were adjusted for age, sex, and BMI to control for potential confounding effects. Statistical significance was set at P < 0.05. All statistical analyses were performed using SPSS for Windows (version 25.0; IBM Corp., Armonk, NY, USA). Results In the comparison of patient demographics, age was the only factor that significantly differed between the mild and severe OA groups (p < 0.001). No significant differences were observed in other factors, as shown in Table 1 (sex, p = 0.292; height, p = 0.052; weight, p = 0.367; BMI, p = 0.052). VAS scores were higher in the severe OA group than in the mild OA group (Fig. 1 ). Figure 2 presents the comparisons of total and domain-specific CSI scores between the two groups. Among the CSI domains, the Headache/Jaw Symptoms score was significantly higher in the mild OA group than in the severe OA group (p < 0.001). However, no significant differences were found in the total CSI score or in the Physical Symptoms, Emotional Distress, and Urological Symptoms domains (total CSI: p = 0.365; Physical Symptoms: p = 0.935; Emotional Distress: p = 0.487; Urological Symptoms: p = 0.224). Multiple regression analysis in the mild OA group identified the Headache/Jaw Symptoms CSI score as the only significant factor influencing VAS scores (β = 0.59, p = 0.034), as shown in Table 2 . In contrast, multiple regression analysis in the severe OA group did not identify any significant factors associated with VAS scores (Table 3 ). Table 1 Patients demographics Mild OA group Severe OA group p-values Sex, female/male, n 29/10 65/12 0.292 Age, years 39.8 ± 2.3 64.9 ± 1.4 < 0.001 Height, cm 160.4 ± 1.1 158.7 ± 1.3 0.052 Weight, kg 57.6 ± 1.7 60.5 ± 1.6 0.367 Body mass index, kg/m 2 22.4 ± 0.5 24.3 ± 0.6 0.052 Tönnis grade (0/ 1/ 2/ 3), n 35/ 4/ 0/ 0 0/ 0/ 15/ 62 < 0.001 Statistically significant P-values (< 0.05) are indicated in bold. OA, osteoarthritis. Table 2 Multiple Regression Analysis Identifying Factors Associated with Hip Pain Intensity in the Mild OA Group Variable β Coefficient 95% CI p-value Age, years 0.01 -0.41 to 0.42 0.978 Sex, female or male -0.27 -0.72 to 0.17 0.217 BMI, kg/m² -0.31 -0.72 to 0.10 0.129 Physical Symptoms CSI Score -0.06 -0.63 to 0.51 0.824 Emotional Distress CSI Score -0.38 -0.88 to 0.12 0.133 Headache/Jaw Symptoms CSI Score 0.59 0.05 to 1.12 0.034 Urological Symptoms CSI Score 0.10 -0.36 to 0.56 0.650 Model R² = 0.335. Adjusted for age, sex, and BMI. Significant values (p < 0.05) are bold. OA, osteoarthritis; CI, confidence interval; BMI, body mass index; CSI, central sensitization inventory. Table 3 Multiple Regression Analysis Identifying Factors Associated with Hip Pain Intensity in the severe OA Group Variable β Coefficient 95% CI p-value Age, years -0.14 -0.39 to 0.12 0.300 Sex, female or male 0.13 -0.11 to 0.37 0.273 BMI, kg/m² -0.12 -0.37 to 0.13 0.338 Physical Symptoms CSI Score -0.31 -0.67 to 0.05 0.086 Emotional Distress CSI Score 0.06 -0.29 to 0.41 0.718 Headache/Jaw Symptoms CSI Score 0.30 -0.02 to 0.62 0.062 Urological Symptoms CSI Score 0.25 -0.03 to 0.53 0.078 Model R² = 0.183. Adjusted for age, sex, and BMI. OA, osteoarthritis; CI, confidence interval; BMI, body mass index; CSI, central sensitization inventory. Discussion Pain in hip OA can arise even in the early stages of the disease and, if not properly managed, may negatively impact both physical symptoms and psychosocial well-being [ 16 ]. Therefore, understanding the underlying mechanisms of hip OA-related pain and implementing timely interventions is essential. The findings of this study suggest that CS plays a key role in the pathophysiology of hip OA pain and provides important insights into how the relationship between clinical symptoms and pain severity differs across stages of OA progression. Previous studies using the CSI have shown that CS-related symptoms influence both pain severity and postoperative outcomes in patients with hip OA, including those with mild conditions such as labral tears as well as severe OA [ 9 – 12 ]. In this study, although total CSI scores did not differ significantly between groups, the Headache/Jaw Symptoms domain score was higher in the mild OA group. Moreover, these symptoms were the only significant factor associated with hip pain intensity in this group. The intra-articular environment differs between mild and severe stages of OA. Previous reports indicate that synovitis and the expression of pain-related cytokines in synovial tissue are more pronounced in mild than in severe OA [ 17 , 18 ]. As synovitis can act as a trigger for CS [ 7 ], this pathophysiological difference may explain why CS-related symptoms were associated with hip pain only in the mild OA group. Although CS-related symptoms may vary among individuals, their contribution to hip pain appears to be influenced by disease stage. Migraines, tension-type headaches, and temporomandibular disorders (TMD) are reported to be more prevalent among middle-aged adults [ 19 – 21 ], which is consistent with the younger age profile of the mild OA group in our study. Age-related susceptibility to these conditions may therefore have contributed to the greater burden of Headache/Jaw Symptoms in mild hip OA. These disorders are prone to chronicity and pain amplification, with CS playing a central role in their pathophysiology [ 22 , 23 ]. They share common mechanisms, particularly involving the trigeminal system and brainstem pain processing centers, which contribute to persistent and widespread pain [ 24 , 25 ]. For example, a study on TMD demonstrated that pain hypersensitivity may extend beyond the temporomandibular joint to the limbs and trunk [ 25 ]. Taken together, these findings highlight the potential role of CS in mild hip OA and suggest that targeted management of comorbid conditions such as migraine, tension-type headache, and TMD may help optimize pain treatment strategies in this population. This study has several limitations. First, its cross-sectional design precludes causal inferences regarding CS and OA progression. It remains unclear whether CS develops early in the disease course or worsens as OA advances. Second, the mild OA group was relatively small, which may have limited statistical power. Larger studies are needed to confirm these results. Finally, the mild OA group was significantly younger, which may have contributed to the higher prevalence of Headache/Jaw Symptoms, as conditions such as migraine, tension-type headache, and TMD are more common in younger populations. This age disparity may have influenced our findings, underscoring the need for future studies with age-matched cohorts. Conclusion This study demonstrated stage-specific differences in CS-related symptoms among patients with hip OA. The mild OA group exhibited higher CSI scores for Headache/Jaw Symptoms, which were associated with hip pain intensity. These results underscore the importance of considering CS in the management of mild hip OA. Declarations Funding: The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Author Contribution YO, KF, GI and MT contributed to the study conception and design. Material preparation, data collection, and analysis were performed by AN, YT, KaU and NT. The first draft of the manuscript was written by YO, and KF, KeU and SA commented on previous versions of the manuscript. All authors read and approved the final manuscript. Data Availability The data underlying this article will be shared on reasonable request to the corresponding author. References Duivenvoorden T, Vissers MM, Verhaar JA et al (2013) Anxiety and depressive symptoms before and after total hip and knee arthroplasty: a prospective multicentre study. Osteoarthritis and cartilage 21(12):1834–1840. https://doi.org/10.1016/j.joca.2013.08.022 Fu K, Makovey J, Metcalf B et al (2019) Sleep Quality and Fatigue Are Associated with Pain Exacerbations of Hip Osteoarthritis: An Internet-based Case-crossover Study. The Journal of rheumatology 46(11):1524–1530. https://doi.org/10.3899/jrheum.181406 Hunter DJ, Guermazi A, Roemer F, Zhang Y, Neogi T (2013) Structural correlates of pain in joints with osteoarthritis. Osteoarthritis and cartilage 21(9):1170–1178. https://doi.org/10.1016/j.joca.2013.05.017 Sofat N, Ejindu V, Kiely, P (2011) What makes osteoarthritis painful? The evidence for local and central pain processing. Rheumatology (Oxford, England) 50(12):2157–2165. https://doi.org/10.1093/rheumatology/ker283 den Boer C, Dries L, Terluin B et al (2019) Central sensitization in chronic pain and medically unexplained symptom research: A systematic review of definitions, operationalizations and measurement instruments. Journal of psychosomatic research 117:32–40. https://doi.org/10.1016/j.jpsychores.2018.12.010 Lluch E, Torres R, Nijs J, Van Oosterwijck J (2014) Evidence for central sensitization in patients with osteoarthritis pain: a systematic literature review. European journal of pain (London, England) 18(10):1367–1375. https://doi.org/10.1002/j.1532-2149.2014.499.x Ohashi Y, Uchida K, Fukushima K, Inoue G, Takaso M (2023) Mechanisms of Peripheral and Central Sensitization in Osteoarthritis Pain. Cureus 15(2):e35331. https://doi.org/10.7759/cureus.35331 Mayer TG, Neblett R, Cohen H et al (2012) The development and psychometric validation of the central sensitization inventory. Pain practice : the official journal of World Institute of Pain 12(4):276–285. https://doi.org/10.1111/j.1533-2500.2011.00493.x Ohashi Y, Fukushima K, Inoue G et al (2020) Central sensitization inventory scores correlate with pain at rest in patients with hip osteoarthritis: a retrospective study. BMC musculoskeletal disorders 21(1):595. https://doi.org/10.1186/s12891-020-03630-6 Ohashi Y, Fukushima K, Uchida K et al (2021) Adverse Effects of Higher Preoperative Pain at Rest, a Central Sensitization-Related Symptom, on Outcomes After Total Hip Arthroplasty in Patients with Osteoarthritis. Journal of pain research 14:3345–3352. https://doi.org/10.2147/JPR.S322314 Bech NH, Sierevelt IN, de Rooij A, Kerkhoffs GMMJ, Haverkamp D (2021) The influence of pain catastrophizing and central sensitization on the reported pain after hip arthroscopy. Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA 29(9):2837–2842. https://doi.org/10.1007/s00167-021-06658-w Perez AR, Baker WF, Patel NK et al (2023) Does central sensitization correlate with two-year postoperative functional outcome scores following hip arthroscopy?. Journal of orthopaedics 49:1–5. https://doi.org/10.1016/j.jor.2023.11.035 Murata Y, Fukase N, Martin M et al (2021) Comparison Between Hip Arthroscopic Surgery and Periacetabular Osteotomy for the Treatment of Patients With Borderline Developmental Dysplasia of the Hip: A Systematic Review. Orthopaedic journal of sports medicine 9(5):23259671211007401. https://doi.org/10.1177/23259671211007401 Kovalenko B, Bremjit P, Fernando N (2018) Classifications in Brief: Tönnis Classification of Hip Osteoarthritis. Clinical orthopaedics and related research 476(8):1680–1684. https://doi.org/10.1097/01.blo.0000534679.75870.5f Tanaka K, Nishigami T, Mibu A et al (2017) Validation of the Japanese version of the Central Sensitization Inventory in patients with musculoskeletal disorders. PloS one 12(12):e0188719. https://doi.org/10.1371/journal.pone.0188719 Gambling TS, Long A (2019) Psycho-social impact of developmental dysplasia of the hip and of differential access to early diagnosis and treatment: A narrative study of young adults. SAGE open medicine 7:2050312119836010. https://doi.org/10.1177/2050312119836010 Koyama T, Uchida K, Fukushima K et al (2021) Elevated levels of TNF-α, IL-1β and IL-6 in the synovial tissue of patients with labral tear: a comparative study with hip osteoarthritis. BMC musculoskeletal disorders 22(1):33. https://doi.org/10.1186/s12891-020-03888-w Benito MJ, Veale DJ, FitzGerald O, van den Berg WB, Bresnihan B (2005) Synovial tissue inflammation in early and late osteoarthritis. Annals of the rheumatic diseases 64(9):1263–1267. https://doi.org/10.1136/ard.2004.025270 Lipton RB, Bigal ME, Diamond M et al (2007) Migraine prevalence, disease burden, and the need for preventive therapy. Neurology 68(5):343–349. https://doi.org/10.1212/01.wnl.0000252808.97649.21 Stovner Lj, Hagen K, Jensen R et al (2007) The global burden of headache: a documentation of headache prevalence and disability worldwide. Cephalalgia : an international journal of headache 27(3):193–210. https://doi.org/10.1111/j.1468-2982.2007.01288.x Gonçalves DA, Camparis CM, Speciali JG, Franco AL, Castanharo SM, Bigal ME (2011) Temporomandibular disorders are differentially associated with headache diagnoses: a controlled study. The Clinical journal of pain 27(7):611–615. https://doi.org/10.1097/AJP.0b013e31820e12f5 Proença JDS, Baad-Hansen L, Braido GVDV, Mercante FG, Campi LB, Gonçalves DAG (2021) Lack of correlation between central sensitization inventory and psychophysical measures of central sensitization in individuals with painful temporomandibular disorder. Archives of oral biology 124:105063. https://doi.org/10.1016/j.archoralbio.2021.105063 Jensen R, Stovner LJ (2008) Epidemiology and comorbidity of headache. The Lancet. Neurology 7(4):354–361. https://doi.org/10.1016/S1474-4422(08)70062-0 Burstein R, Noseda R, Borsook D (2015) Migraine: multiple processes, complex pathophysiology. The Journal of neuroscience : the official journal of the Society for Neuroscience 35(17):6619–6629. https://doi.org/10.1523/JNEUROSCI.0373-15.2015 Sarlani E, Greenspan JD (2003) Evidence for generalized hyperalgesia in temporomandibular disorders patients. Pain 102 (3):221–226. https://doi.org/10.1016/S0304-3959(03)00095-2 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 13 Nov, 2025 Reviewers agreed at journal 07 Nov, 2025 Reviewers invited by journal 05 Nov, 2025 Editor invited by journal 04 Nov, 2025 Editor assigned by journal 03 Nov, 2025 Submission checks completed at journal 03 Nov, 2025 First submitted to journal 30 Oct, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7986921","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":545570204,"identity":"bcff0e12-b2f5-4eaa-8010-4db97a49b912","order_by":0,"name":"Yoshihisa Ohashi","email":"data:image/png;base64,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","orcid":"","institution":"Kitasato University School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Yoshihisa","middleName":"","lastName":"Ohashi","suffix":""},{"id":545570205,"identity":"7848c191-6813-41e8-9ffc-ca39b0cba135","order_by":1,"name":"Kensuke Fukushima","email":"","orcid":"","institution":"Kitasato University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Kensuke","middleName":"","lastName":"Fukushima","suffix":""},{"id":545570206,"identity":"8ce5a3e5-6460-4577-8cae-dd9f6e753374","order_by":2,"name":"Stephen K. Aoki","email":"","orcid":"","institution":"University of Utah","correspondingAuthor":false,"prefix":"","firstName":"Stephen","middleName":"K.","lastName":"Aoki","suffix":""},{"id":545570208,"identity":"6fe8e4a9-169a-4d4f-96b6-759019e470fb","order_by":3,"name":"Kentaro Uchida","email":"","orcid":"","institution":"Kitasato University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Kentaro","middleName":"","lastName":"Uchida","suffix":""},{"id":545570210,"identity":"6dc0e975-35ba-4278-a68b-97c15416e919","order_by":4,"name":"Yoji Toyomura","email":"","orcid":"","institution":"Kitasato University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yoji","middleName":"","lastName":"Toyomura","suffix":""},{"id":545570211,"identity":"19bba39c-a953-4d3b-86b6-c6feaa6ca39d","order_by":5,"name":"Akira Norisugi","email":"","orcid":"","institution":"Kitasato University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Akira","middleName":"","lastName":"Norisugi","suffix":""},{"id":545570212,"identity":"fc2bd057-efed-4a2d-9dbd-6fea87dfa285","order_by":6,"name":"Katsufumi Uchiyama","email":"","orcid":"","institution":"Kitasato University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Katsufumi","middleName":"","lastName":"Uchiyama","suffix":""},{"id":545570213,"identity":"47ccb843-5a48-442e-aa48-47b6086a86f9","order_by":7,"name":"Naonobu Takahira","email":"","orcid":"","institution":"Kitasato University School of Allied Health Science","correspondingAuthor":false,"prefix":"","firstName":"Naonobu","middleName":"","lastName":"Takahira","suffix":""},{"id":545570214,"identity":"01f9f2f1-618a-4d09-8ccc-67e713849558","order_by":8,"name":"Gen Inoue","email":"","orcid":"","institution":"Kitasato University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Gen","middleName":"","lastName":"Inoue","suffix":""},{"id":545570215,"identity":"515872c3-025a-42aa-8c6c-3282827b3358","order_by":9,"name":"Masashi Takaso","email":"","orcid":"","institution":"Kitasato University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Masashi","middleName":"","lastName":"Takaso","suffix":""}],"badges":[],"createdAt":"2025-10-30 08:38:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7986921/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7986921/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":96156708,"identity":"1ad237d4-79a8-4048-9235-36993ef8e181","added_by":"auto","created_at":"2025-11-18 08:30:31","extension":"tif","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":361646,"visible":true,"origin":"","legend":"","description":"","filename":"Figure1.tif","url":"https://assets-eu.researchsquare.com/files/rs-7986921/v1/e66fe0b78c6a74cc1cb19d0e.tif"},{"id":96251006,"identity":"e66fe738-46fa-4a59-92fa-e90c58fb879f","added_by":"auto","created_at":"2025-11-19 07:39:13","extension":"tif","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":423716,"visible":true,"origin":"","legend":"","description":"","filename":"Figure2.tif","url":"https://assets-eu.researchsquare.com/files/rs-7986921/v1/dce6f2f170a87b14a8a78697.tif"},{"id":96156709,"identity":"f4c4e36d-424e-4c15-ac52-78a7ff6361e5","added_by":"auto","created_at":"2025-11-18 08:30:31","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":17063,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.docx","url":"https://assets-eu.researchsquare.com/files/rs-7986921/v1/da6460ac2c95d9c5bba6b97f.docx"},{"id":96156711,"identity":"24bd3220-fb2f-412b-a8be-2f126dc484ba","added_by":"auto","created_at":"2025-11-18 08:30:31","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":33115,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript1.docx","url":"https://assets-eu.researchsquare.com/files/rs-7986921/v1/8afadb4b2776e170e3d05d64.docx"},{"id":96251047,"identity":"ad49f646-431e-4aac-b826-3e72bf8f8f56","added_by":"auto","created_at":"2025-11-19 07:39:15","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":17620,"visible":true,"origin":"","legend":"","description":"","filename":"Table2.docx","url":"https://assets-eu.researchsquare.com/files/rs-7986921/v1/b9cda3e3cedfac0501b4136c.docx"},{"id":96156710,"identity":"2b535697-e6c0-44a0-859f-7578de76f153","added_by":"auto","created_at":"2025-11-18 08:30:31","extension":"docx","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":17592,"visible":true,"origin":"","legend":"","description":"","filename":"Table3.docx","url":"https://assets-eu.researchsquare.com/files/rs-7986921/v1/83c38731cfbbb6dd19c42834.docx"},{"id":96249163,"identity":"86117889-f4ad-4ab0-b883-9a04acbea83c","added_by":"auto","created_at":"2025-11-19 07:30:29","extension":"json","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":10432,"visible":true,"origin":"","legend":"","description":"","filename":"2ccdaab9d29742bca15fc93554c2faae.json","url":"https://assets-eu.researchsquare.com/files/rs-7986921/v1/99c6485c0b761c7e0bd5b9f8.json"},{"id":96251041,"identity":"d6752759-dff7-4d08-aa87-c7f2aeeeba20","added_by":"auto","created_at":"2025-11-19 07:39:15","extension":"xml","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":73794,"visible":true,"origin":"","legend":"","description":"","filename":"2ccdaab9d29742bca15fc93554c2faae1enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-7986921/v1/bd27f45df4833c892cdcafbf.xml"},{"id":96251929,"identity":"345becc1-8836-4f92-85cd-8ee7023c5326","added_by":"auto","created_at":"2025-11-19 07:40:11","extension":"tif","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":361646,"visible":true,"origin":"","legend":"","description":"","filename":"Figure1.tif","url":"https://assets-eu.researchsquare.com/files/rs-7986921/v1/a081c48ee195f7ae860a700f.tif"},{"id":96156718,"identity":"879455dd-c14d-439b-97d3-40b486617101","added_by":"auto","created_at":"2025-11-18 08:30:31","extension":"tif","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":423716,"visible":true,"origin":"","legend":"","description":"","filename":"Figure2.tif","url":"https://assets-eu.researchsquare.com/files/rs-7986921/v1/f09602d8599865bedf2fc982.tif"},{"id":96156715,"identity":"f58f7bdd-f855-48e7-9234-75ca7064d0b7","added_by":"auto","created_at":"2025-11-18 08:30:31","extension":"png","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":32451,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-7986921/v1/f1668d133169fe674412cda1.png"},{"id":96156716,"identity":"1188f00e-9e0c-4dd0-a3e8-8747aed96976","added_by":"auto","created_at":"2025-11-18 08:30:31","extension":"png","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":37121,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure2.png","url":"https://assets-eu.researchsquare.com/files/rs-7986921/v1/da829f98ae0a60b829cfa146.png"},{"id":96156717,"identity":"22f85b25-ac33-44e2-85a6-915bb17d780a","added_by":"auto","created_at":"2025-11-18 08:30:31","extension":"xml","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":72760,"visible":true,"origin":"","legend":"","description":"","filename":"2ccdaab9d29742bca15fc93554c2faae1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7986921/v1/cdb3162121b4dda39b346a7d.xml"},{"id":96156719,"identity":"c39f8bb7-326c-45a6-b5b4-5a25c6a62aac","added_by":"auto","created_at":"2025-11-18 08:30:32","extension":"html","order_by":13,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":83661,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7986921/v1/3fd515066983803aa589160a.html"},{"id":96156704,"identity":"5fcda280-c55e-46e5-9d8a-c78d661372f2","added_by":"auto","created_at":"2025-11-18 08:30:31","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":39488,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of Visual Analog Scale (VAS) Scores Between the Mild and Severe Osteoarthritis (OA) Groups. The mean VAS scores for hip pain were significantly higher in the severe OA group compared to the mild OA group. Bars within the boxes represent the mean, and error bars indicate standard error. *, p \u0026lt; 0.05.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-7986921/v1/9e3a53c18590acb9abd3e7cf.png"},{"id":96156705,"identity":"66ad4aaf-3b33-4731-be11-54377648224b","added_by":"auto","created_at":"2025-11-18 08:30:31","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":59613,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of Total and Domain-Specific Central Sensitization Inventory (CSI) Scores Between the Mild and Severe Osteoarthritis (OA) Groups. Total CSI scores and domain-specific CSI scores (Physical Symptoms, Emotional Distress, Headache/Jaw Symptoms, and Urological Symptoms) were compared between the mild OA and severe OA groups. The Headache/Jaw Symptoms score was significantly higher in the mild OA group compared to the severe OA group. *, p \u0026lt; 0.001. Bars within the boxes represent the means, and error bars indicate standard error.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-7986921/v1/3d7d4b444a2baa6b1480190a.png"},{"id":96256906,"identity":"ea204152-a04d-49d5-b3bc-a1c8588f5c39","added_by":"auto","created_at":"2025-11-19 07:50:54","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":629169,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7986921/v1/07ca282b-30a9-480e-93a5-e68015a25fb9.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical Impact of Stage-Specific Central Sensitization-Related Symptoms in Hip Osteoarthritis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHip osteoarthritis (OA) is a progressive joint disease that not only causes chronic pain but is also frequently accompanied by various physical symptoms and/or emotional distress [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. These factors can influence pain severity and substantially reduce quality of life. Such complex symptomatology cannot be fully explained by structural joint damage alone [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], suggesting that additional mechanisms contribute to the overall disease burden in hip OA.\u003c/p\u003e\u003cp\u003eCentral sensitization (CS) refers to an amplification of pain signaling within the central nervous system and is considered to play an important role not only in chronic pain but also in a range of clinical symptoms in musculoskeletal disorders, including hip OA [\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The Central Sensitization Inventory (CSI), a patient-reported outcome measure, enables the assessment of diverse CS-related symptoms [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Previous studies have reported associations between CSI scores, hip pain severity, and poor postoperative outcomes in patients with hip OA across different disease stages [\u003cspan additionalcitationids=\"CR10 CR11\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. However, differences in the characteristics of CS-related symptoms across disease stages of hip OA have not yet been fully elucidated. Understanding the stage-specific features of CS-related symptoms and their relationships with hip pain is crucial for developing tailored treatment strategies for patients with hip OA.\u003c/p\u003e\u003cp\u003eThus, the aim of this study was to compare the characteristics of CS-related symptoms mild and severe stages of hip OA and to clarify their associations with pain, using the CSI.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eParticipants\u003c/h2\u003e\u003cp\u003e This study was approved by our Institutional Review Board, and all patients provided informed consent. The study was conducted in accordance with the Declaration of Helsinki. We enrolled 180 consecutive patients with hip OA scheduled to undergo unilateral hip arthroscopy, periacetabular osteotomy, or total hip arthroplasty (THA). To minimize heterogeneity in disease etiology, we included patients with unilateral hip OA secondary to acetabular dysplasia (AD) or borderline AD, defined by a center-edge (CE) angle of \u0026le;\u0026thinsp;25\u0026deg; [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Exclusion criteria included bilateral hip OA, previous hip surgery, and a history of rheumatologic disease. Consequently, we excluded 37 patients with bilateral hip OA, 17 patients with a CE angle\u0026thinsp;\u0026gt;\u0026thinsp;25\u0026deg;, 5 patients with a history of previous surgery on the affected hip, and 5 patients with rheumatoid arthritis. This resulted in a final cohort of 116 participants. Hip OA severity was assessed radiographically using the T\u0026ouml;nnis classification system [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Based on this system, 39 patients with T\u0026ouml;nnis grade 0 or 1 were classified into the mild OA group, while 77 patients with T\u0026ouml;nnis grade 2 or 3 were assigned to the severe OA group.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eClinical Assessments\u003c/h3\u003e\n\u003cp\u003eThe CSI consists of 25 self-reported items evaluating CS-related symptoms, each rated on a 5-point Likert scale (0\u0026thinsp;=\u0026thinsp;never, 1\u0026thinsp;=\u0026thinsp;rarely, 2\u0026thinsp;=\u0026thinsp;sometimes, 3\u0026thinsp;=\u0026thinsp;often, 4\u0026thinsp;=\u0026thinsp;always) [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The total CSI score ranges from 0 to 100, with higher scores indicating greater symptom severity. The CSI is categorized into four symptom domains: Physical Symptoms (8 items: Q1, Q2, Q8, Q9, Q12, Q17, Q18, Q23), Emotional Distress (6 items: Q3, Q6, Q13, Q15, Q16, Q24), Headache/Jaw Symptoms (5 items: Q4, Q7, Q10, Q19, Q20), and Urological Symptoms (3 items: Q11, Q21, Q25) [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In this study, CSI scores were analyzed by domain, with participants independently completing the validated CSI Japanese version [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Domain-specific and total CSI scores were compared between the mild OA and severe OA groups. Hip pain intensity was assessed using the Visual Analog Scale (VAS). Associations between hip pain intensity and domain-specific CSI scores were evaluated within each group. The CSI score and VAS score assessments were conducted one month preoperatively.\u003c/p\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eResults are expressed as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard errors of the mean unless otherwise indicated. Patient demographics, VAS scores, total CSI scores, and domain-specific CSI scores were compared between the mild OA group and the severe OA group. The normality of continuous variables was assessed using the Shapiro-Wilk test. Since the data were not normally distributed, the Mann-Whitney U test was used for continuous variables, while the χ\u0026sup2; test was applied for categorical variables. Multivariate regression analyses were conducted to identify factors influencing VAS scores. This analysis was performed separately for the mild OA group and the severe OA group. The four CSI domains (Physical Symptoms, Emotional Distress, Headache/Jaw Symptoms, and Urological Symptoms) were used as explanatory variables, with VAS score as the dependent variable. The models were adjusted for age, sex, and BMI to control for potential confounding effects. Statistical significance was set at P\u0026thinsp;\u0026lt;\u0026thinsp;0.05. All statistical analyses were performed using SPSS for Windows (version 25.0; IBM Corp., Armonk, NY, USA).\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eIn the comparison of patient demographics, age was the only factor that significantly differed between the mild and severe OA groups (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). No significant differences were observed in other factors, as shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e (sex, p\u0026thinsp;=\u0026thinsp;0.292; height, p\u0026thinsp;=\u0026thinsp;0.052; weight, p\u0026thinsp;=\u0026thinsp;0.367; BMI, p\u0026thinsp;=\u0026thinsp;0.052). VAS scores were higher in the severe OA group than in the mild OA group (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Figure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e presents the comparisons of total and domain-specific CSI scores between the two groups. Among the CSI domains, the Headache/Jaw Symptoms score was significantly higher in the mild OA group than in the severe OA group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). However, no significant differences were found in the total CSI score or in the Physical Symptoms, Emotional Distress, and Urological Symptoms domains (total CSI: p\u0026thinsp;=\u0026thinsp;0.365; Physical Symptoms: p\u0026thinsp;=\u0026thinsp;0.935; Emotional Distress: p\u0026thinsp;=\u0026thinsp;0.487; Urological Symptoms: p\u0026thinsp;=\u0026thinsp;0.224). Multiple regression analysis in the mild OA group identified the Headache/Jaw Symptoms CSI score as the only significant factor influencing VAS scores (β\u0026thinsp;=\u0026thinsp;0.59, p\u0026thinsp;=\u0026thinsp;0.034), as shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e2\u003c/span\u003e. In contrast, multiple regression analysis in the severe OA group did not identify any significant factors associated with VAS scores (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003ePatients demographics\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMild OA group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSevere OA group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-values\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex, female/male, n\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e29/10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e65/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.292\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge, years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e39.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e64.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeight, cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e160.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e158.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.052\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWeight, kg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e57.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e60.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.367\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBody mass index, kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.052\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eT\u0026ouml;nnis grade (0/ 1/ 2/ 3), n\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e35/ 4/ 0/ 0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0/ 0/ 15/ 62\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eStatistically significant P-values (\u0026lt;\u0026thinsp;0.05) are indicated in bold. OA, osteoarthritis.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMultiple Regression Analysis Identifying Factors Associated with Hip Pain Intensity in the Mild OA Group\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eβ Coefficient\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge, years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.41 to 0.42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.978\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex, female or male\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.72 to 0.17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.217\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI, kg/m\u0026sup2;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.72 to 0.10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.129\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePhysical Symptoms CSI Score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.63 to 0.51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.824\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEmotional Distress CSI Score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.88 to 0.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.133\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHeadache/Jaw Symptoms CSI Score\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e0.59\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e0.05 to 1.12\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.034\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUrological Symptoms CSI Score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.36 to 0.56\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.650\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eModel R\u0026sup2; = 0.335. Adjusted for age, sex, and BMI. Significant values (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) are bold. OA, osteoarthritis; CI, confidence interval; BMI, body mass index; CSI, central sensitization inventory.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMultiple Regression Analysis Identifying Factors Associated with Hip Pain Intensity in the severe OA Group\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eβ Coefficient\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge, years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.39 to 0.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.300\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex, female or male\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.11 to 0.37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.273\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI, kg/m\u0026sup2;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.37 to 0.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.338\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePhysical Symptoms CSI Score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.67 to 0.05\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.086\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEmotional Distress CSI Score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.29 to 0.41\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.718\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeadache/Jaw Symptoms CSI Score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.02 to 0.62\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.062\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUrological Symptoms CSI Score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.03 to 0.53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.078\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eModel R\u0026sup2; = 0.183. Adjusted for age, sex, and BMI. OA, osteoarthritis; CI, confidence interval; BMI, body mass index; CSI, central sensitization inventory.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003ePain in hip OA can arise even in the early stages of the disease and, if not properly managed, may negatively impact both physical symptoms and psychosocial well-being [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Therefore, understanding the underlying mechanisms of hip OA-related pain and implementing timely interventions is essential. The findings of this study suggest that CS plays a key role in the pathophysiology of hip OA pain and provides important insights into how the relationship between clinical symptoms and pain severity differs across stages of OA progression.\u003c/p\u003e\u003cp\u003ePrevious studies using the CSI have shown that CS-related symptoms influence both pain severity and postoperative outcomes in patients with hip OA, including those with mild conditions such as labral tears as well as severe OA [\u003cspan additionalcitationids=\"CR10 CR11\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In this study, although total CSI scores did not differ significantly between groups, the Headache/Jaw Symptoms domain score was higher in the mild OA group. Moreover, these symptoms were the only significant factor associated with hip pain intensity in this group. The intra-articular environment differs between mild and severe stages of OA. Previous reports indicate that synovitis and the expression of pain-related cytokines in synovial tissue are more pronounced in mild than in severe OA [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. As synovitis can act as a trigger for CS [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], this pathophysiological difference may explain why CS-related symptoms were associated with hip pain only in the mild OA group. Although CS-related symptoms may vary among individuals, their contribution to hip pain appears to be influenced by disease stage.\u003c/p\u003e\u003cp\u003eMigraines, tension-type headaches, and temporomandibular disorders (TMD) are reported to be more prevalent among middle-aged adults [\u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], which is consistent with the younger age profile of the mild OA group in our study. Age-related susceptibility to these conditions may therefore have contributed to the greater burden of Headache/Jaw Symptoms in mild hip OA. These disorders are prone to chronicity and pain amplification, with CS playing a central role in their pathophysiology [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. They share common mechanisms, particularly involving the trigeminal system and brainstem pain processing centers, which contribute to persistent and widespread pain [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. For example, a study on TMD demonstrated that pain hypersensitivity may extend beyond the temporomandibular joint to the limbs and trunk [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Taken together, these findings highlight the potential role of CS in mild hip OA and suggest that targeted management of comorbid conditions such as migraine, tension-type headache, and TMD may help optimize pain treatment strategies in this population.\u003c/p\u003e\u003cp\u003eThis study has several limitations. First, its cross-sectional design precludes causal inferences regarding CS and OA progression. It remains unclear whether CS develops early in the disease course or worsens as OA advances. Second, the mild OA group was relatively small, which may have limited statistical power. Larger studies are needed to confirm these results. Finally, the mild OA group was significantly younger, which may have contributed to the higher prevalence of Headache/Jaw Symptoms, as conditions such as migraine, tension-type headache, and TMD are more common in younger populations. This age disparity may have influenced our findings, underscoring the need for future studies with age-matched cohorts.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study demonstrated stage-specific differences in CS-related symptoms among patients with hip OA. The mild OA group exhibited higher CSI scores for Headache/Jaw Symptoms, which were associated with hip pain intensity. These results underscore the importance of considering CS in the management of mild hip OA.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFunding:\u003c/h2\u003e\u003cp\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eYO, KF, GI and MT contributed to the study conception and design. Material preparation, data collection, and analysis were performed by AN, YT, KaU and NT. The first draft of the manuscript was written by YO, and KF, KeU and SA commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe data underlying this article will be shared on reasonable request to the corresponding author.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eDuivenvoorden T, Vissers MM, Verhaar JA et al (2013) Anxiety and depressive symptoms before and after total hip and knee arthroplasty: a prospective multicentre study. Osteoarthritis and cartilage 21(12):1834\u0026ndash;1840. https://doi.org/10.1016/j.joca.2013.08.022\u003c/li\u003e\n\u003cli\u003eFu K, Makovey J, Metcalf B et al (2019) Sleep Quality and Fatigue Are Associated with Pain Exacerbations of Hip Osteoarthritis: An Internet-based Case-crossover Study. The Journal of rheumatology 46(11):1524\u0026ndash;1530. https://doi.org/10.3899/jrheum.181406\u003c/li\u003e\n\u003cli\u003eHunter DJ, Guermazi A, Roemer F, Zhang Y, Neogi T (2013) Structural correlates of pain in joints with osteoarthritis. Osteoarthritis and cartilage 21(9):1170\u0026ndash;1178. https://doi.org/10.1016/j.joca.2013.05.017\u003c/li\u003e\n\u003cli\u003eSofat N, Ejindu V, Kiely, P (2011) What makes osteoarthritis painful? The evidence for local and central pain processing. Rheumatology (Oxford, England) 50(12):2157\u0026ndash;2165. https://doi.org/10.1093/rheumatology/ker283\u003c/li\u003e\n\u003cli\u003eden Boer C, Dries L, Terluin B et al (2019) Central sensitization in chronic pain and medically unexplained symptom research: A systematic review of definitions, operationalizations and measurement instruments. Journal of psychosomatic research 117:32\u0026ndash;40. https://doi.org/10.1016/j.jpsychores.2018.12.010\u003c/li\u003e\n\u003cli\u003eLluch E, Torres R, Nijs J, Van Oosterwijck J (2014) Evidence for central sensitization in patients with osteoarthritis pain: a systematic literature review. European journal of pain (London, England) 18(10):1367\u0026ndash;1375. https://doi.org/10.1002/j.1532-2149.2014.499.x\u003c/li\u003e\n\u003cli\u003eOhashi Y, Uchida K, Fukushima K, Inoue G, Takaso M (2023) Mechanisms of Peripheral and Central Sensitization in Osteoarthritis Pain. Cureus 15(2):e35331. https://doi.org/10.7759/cureus.35331\u003c/li\u003e\n\u003cli\u003eMayer TG, Neblett R, Cohen H et al (2012) The development and psychometric validation of the central sensitization inventory. Pain practice : the official journal of World Institute of Pain 12(4):276\u0026ndash;285. https://doi.org/10.1111/j.1533-2500.2011.00493.x\u003c/li\u003e\n\u003cli\u003eOhashi Y, Fukushima K, Inoue G et al (2020) Central sensitization inventory scores correlate with pain at rest in patients with hip osteoarthritis: a retrospective study. BMC musculoskeletal disorders 21(1):595. https://doi.org/10.1186/s12891-020-03630-6\u003c/li\u003e\n\u003cli\u003eOhashi Y, Fukushima K, Uchida K et al (2021) Adverse Effects of Higher Preoperative Pain at Rest, a Central Sensitization-Related Symptom, on Outcomes After Total Hip Arthroplasty in Patients with Osteoarthritis. Journal of pain research 14:3345\u0026ndash;3352. https://doi.org/10.2147/JPR.S322314\u003c/li\u003e\n\u003cli\u003eBech NH, Sierevelt IN, de Rooij A, Kerkhoffs GMMJ, Haverkamp D (2021) The influence of pain catastrophizing and central sensitization on the reported pain after hip arthroscopy. Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA 29(9):2837\u0026ndash;2842. https://doi.org/10.1007/s00167-021-06658-w\u003c/li\u003e\n\u003cli\u003ePerez AR, Baker WF, Patel NK et al (2023) Does central sensitization correlate with two-year postoperative functional outcome scores following hip arthroscopy?. Journal of orthopaedics 49:1\u0026ndash;5. https://doi.org/10.1016/j.jor.2023.11.035\u003c/li\u003e\n\u003cli\u003eMurata Y, Fukase N, Martin M et al (2021) Comparison Between Hip Arthroscopic Surgery and Periacetabular Osteotomy for the Treatment of Patients With Borderline Developmental Dysplasia of the Hip: A Systematic Review. Orthopaedic journal of sports medicine 9(5):23259671211007401. https://doi.org/10.1177/23259671211007401\u003c/li\u003e\n\u003cli\u003eKovalenko B, Bremjit P, Fernando N (2018) Classifications in Brief: T\u0026ouml;nnis Classification of Hip Osteoarthritis. Clinical orthopaedics and related research 476(8):1680\u0026ndash;1684. https://doi.org/10.1097/01.blo.0000534679.75870.5f\u003c/li\u003e\n\u003cli\u003eTanaka K, Nishigami T, Mibu A et al (2017) Validation of the Japanese version of the Central Sensitization Inventory in patients with musculoskeletal disorders. PloS one 12(12):e0188719. https://doi.org/10.1371/journal.pone.0188719\u003c/li\u003e\n\u003cli\u003eGambling TS, Long A (2019) Psycho-social impact of developmental dysplasia of the hip and of differential access to early diagnosis and treatment: A narrative study of young adults. SAGE open medicine 7:2050312119836010. https://doi.org/10.1177/2050312119836010\u003c/li\u003e\n\u003cli\u003eKoyama T, Uchida K, Fukushima K et al (2021) Elevated levels of TNF-\u0026alpha;, IL-1\u0026beta; and IL-6 in the synovial tissue of patients with labral tear: a comparative study with hip osteoarthritis. BMC musculoskeletal disorders 22(1):33. https://doi.org/10.1186/s12891-020-03888-w\u003c/li\u003e\n\u003cli\u003eBenito MJ, Veale DJ, FitzGerald O, van den Berg WB, Bresnihan B (2005) Synovial tissue inflammation in early and late osteoarthritis. Annals of the rheumatic diseases 64(9):1263\u0026ndash;1267. https://doi.org/10.1136/ard.2004.025270\u003c/li\u003e\n\u003cli\u003eLipton RB, Bigal ME, Diamond M et al (2007) Migraine prevalence, disease burden, and the need for preventive therapy. Neurology 68(5):343\u0026ndash;349. https://doi.org/10.1212/01.wnl.0000252808.97649.21\u003c/li\u003e\n\u003cli\u003eStovner Lj, Hagen K, Jensen R et al (2007) The global burden of headache: a documentation of headache prevalence and disability worldwide. Cephalalgia : an international journal of headache 27(3):193\u0026ndash;210. https://doi.org/10.1111/j.1468-2982.2007.01288.x\u003c/li\u003e\n\u003cli\u003eGon\u0026ccedil;alves DA, Camparis CM, Speciali JG, Franco AL, Castanharo SM, Bigal ME (2011) Temporomandibular disorders are differentially associated with headache diagnoses: a controlled study. The Clinical journal of pain 27(7):611\u0026ndash;615. https://doi.org/10.1097/AJP.0b013e31820e12f5\u003c/li\u003e\n\u003cli\u003eProen\u0026ccedil;a JDS, Baad-Hansen L, Braido GVDV, Mercante FG, Campi LB, Gon\u0026ccedil;alves DAG (2021) Lack of correlation between central sensitization inventory and psychophysical measures of central sensitization in individuals with painful temporomandibular disorder. Archives of oral biology 124:105063. https://doi.org/10.1016/j.archoralbio.2021.105063\u003c/li\u003e\n\u003cli\u003eJensen R, Stovner LJ (2008) Epidemiology and comorbidity of headache. The Lancet. Neurology 7(4):354\u0026ndash;361. https://doi.org/10.1016/S1474-4422(08)70062-0\u003c/li\u003e\n\u003cli\u003eBurstein R, Noseda R, Borsook D (2015) Migraine: multiple processes, complex pathophysiology. The Journal of neuroscience : the official journal of the Society for Neuroscience 35(17):6619\u0026ndash;6629. https://doi.org/10.1523/JNEUROSCI.0373-15.2015\u003c/li\u003e\n\u003cli\u003eSarlani E, Greenspan JD (2003) Evidence for generalized hyperalgesia in temporomandibular disorders patients. \u003cem\u003ePain\u003c/em\u003e \u003cem\u003e102\u003c/em\u003e(3):221\u0026ndash;226. https://doi.org/10.1016/S0304-3959(03)00095-2\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Hip osteoarthritis, Central sensitization, Headache, Temporomandibular disorders, Hip pain","lastPublishedDoi":"10.21203/rs.3.rs-7986921/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7986921/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e\u003cp\u003eThis study aimed to compare the characteristics of central sensitization (CS)-related symptoms between mild and severe hip osteoarthritis (OA) and to clarify their associations with hip pain.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eA total of 116 patients with unilateral hip OA secondary to acetabular dysplasia or borderline dysplasia (center-edge angle\u0026thinsp;\u0026le;\u0026thinsp;25\u0026deg;) were enrolled. Patients were classified into mild (T\u0026ouml;nnis grade 0\u0026ndash;1, n\u0026thinsp;=\u0026thinsp;39) and severe (T\u0026ouml;nnis grade 2\u0026ndash;3, n\u0026thinsp;=\u0026thinsp;77) OA groups. CS-related symptoms were assessed using the Central Sensitization Inventory (CSI), including domain-specific scores (Physical Symptoms, Emotional Distress, Headache/Jaw Symptoms, and Urological Symptoms). Hip pain intensity was evaluated with the Visual Analog Scale (VAS). Between-group comparisons were conducted, and multivariate regression analyses were performed to examine the associations between CSI domain scores and VAS.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eVAS scores were higher in the severe OA group than in the mild OA group. Total CSI scores did not differ significantly between groups. However, the Headache/Jaw Symptoms domain score was significantly higher in the mild OA group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and was the only domain independently associated with hip pain intensity in this group (β\u0026thinsp;=\u0026thinsp;0.59, p\u0026thinsp;=\u0026thinsp;0.034). No significant associations were observed in the severe OA group.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eCS-related symptoms, particularly headache and jaw complaints, play an important role in pain perception in mild hip OA. Evaluating and managing these symptoms may help optimize stage-specific pain treatment strategies for patients with hip OA.\u003c/p\u003e","manuscriptTitle":"Clinical Impact of Stage-Specific Central Sensitization-Related Symptoms in Hip Osteoarthritis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-18 08:30:26","doi":"10.21203/rs.3.rs-7986921/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2025-11-14T02:54:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"253819124575055183057838952585168950512","date":"2025-11-07T22:28:40+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-05T15:02:33+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-11-04T18:13:09+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-03T11:12:32+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-03T11:10:38+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-10-30T08:23:20+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"87d5a2df-3c89-471e-af94-a0a4ed17ee6e","owner":[],"postedDate":"November 18th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":58046722,"name":"Health sciences/Diseases"},{"id":58046723,"name":"Health sciences/Health care"},{"id":58046724,"name":"Health sciences/Medical research"},{"id":58046725,"name":"Health sciences/Rheumatology"},{"id":58046726,"name":"Health sciences/Signs and symptoms"}],"tags":[],"updatedAt":"2025-11-18T08:30:27+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-18 08:30:26","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7986921","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7986921","identity":"rs-7986921","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}