Assessment of the elasticity of lipedematous tissue and the examination of the relationship between pain and fibrosis in lipedema

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The symptom that most significantly affects the quality of life is pain. Ultrasound elastography is an imaging technology that allows for measuring tissue stiffness quantitatively. This study aims to evaluate the relationship between accompanying pain in patients with lipedema and tissue elasticity measured using shear-wave elastography (SWE). Methods: Our study was designed as an observational, analytical and cross-sectional study. The visual analog scale (VAS) was used to assess pain, while the PainDetect questionnaire was utilized to evaluate neuropathic pain. The evaluation of tissue elasticity and fibrosis was conducted using the SWE method. Results: This research assessed thirty-five patients, revealing an average age of 45.2 years and an average VKI of 33.6 kg/m². 60% of the patients had a lipedema diagnosis in their family history. Both age (p<0.01) and BMI (p<0.001) values were moderately correlated with all subcutaneous adipose tissue measurements, while no correlation was observed in SWE measurements. Only the level of the thigh in the SWE-Elasticity (SWE-E) values was related to VAS (p=0.03). Additionally, PainDetect data revealed correlations with SWE-Velocity (SWE-V) and SWE-E in both the right and left thighs. Conclusions: While SWE measurements were not correlated with skin adipose tissue, SWE measurements were correlated with pain and neuropathic pain in patients with lipedema. This finding highlights a potentially important relationship between tissue elasticity and pain, which may warrant further exploration. Health sciences/Medical research/Clinical trial design/Clinical trials Health sciences/Health care/Diagnosis Figures Figure 1 Introduction Lipedema is a chronic and progressive disorder of adipose tissue characterized by the abnormal accumulation of subcutaneous fat, predominantly in the legs and occasionally in the arms. Mainly affecting women, this condition is often misidentified as obesity or lymphedema. The underlying cause is poorly understood. The precise prevalence of lipedema within the general population remains unclear; however, studies indicate that the occurrence of a positive family history ranges from 16–64% ( 1 – 10 ). Lipedema is often recognized as emerging during crucial periods of hormonal change, especially during puberty, pregnancy, or menopause. Individuals diagnosed with lipedema frequently report experiencing discomfort, easy bruising, and tenderness in their enlarged legs. These symptoms may progress to severe pain and may result in restricted mobility. In addition to physical complications, lipedema can also cause psychological distress. ( 1 – 7 , 9 – 18 ). The symptom that most profoundly impacts daily life is pain. The precise causes of pain associated with lipedema are still not fully understood. Excess fat accumulation in specific body regions triggers low-grade chronic inflammation, disrupting adipocyte metabolism. This disruption leads to increased oxidative damage to lipids and localized hypoxia ( 4 , 12 , 14 ). Sympathetic and sensory nerves innervate subcutaneous adipose tissue, while adipocytes synthesize and secrete neurotrophic factors that modulate sensory innervation. ( 12 , 14 ) Estrogen may play a critical role in the sympathetic nervous system's innervation of subcutaneous adipose tissue, potentially leading to innervation abnormalities and sensory nerve inflammation. ( 2 , 11 , 12 , 17 ). The Neuropathic Pain Special Interest Group (NeuPSIG) of the International Association for the Study of Pain (IASP) defines neuropathic pain as "pain resulting directly from a lesion or disease that affects the somatosensory system."( 19 – 21 ). Individuals with lipedema frequently experience pain in the affected areas that is both allodynic and neuropathic in nature ( 22 ). There is still a limited understanding of the factors associated with pain in lipedema. Recognizing and comprehending the elements contributing to pain linked with lipedema may assist in precisely evaluating the severity of the condition. Lipedema is characterized by an increase in skin thickness and a reduction in echogenicity within the subcutaneous tissue. High-frequency ultrasound imaging is an effective tool for visualizing subcutaneous adipose tissue. It enables a comprehensive assessment of the thickness and characteristics of fat layers, thereby facilitating a better understanding of tissue composition ( 9 ). Ultrasound elastography is an imaging technology that allows for the quantitative measurement of tissue stiffness ( 23 , 24 ). This study aimed to investigate the relationship between accompanying pain in patients with lipedema and tissue elasticity, as measured using shear-wave elastography (SWE). Methods A cross-sectional, observational, and analytical study was conducted in the outpatient clinic of Ankara Etlik City Hospital's Clinic of Physical Medicine and Rehabilitation between June and December 2024. Approval for the study was granted by the local ethical committee (AESH-BADEK-2024-395). The study was conducted in accordance with the principles of the Declaration of Helsinki. A written informed consent was obtained from each patient. Due to the lack of previous studies employing elastography specifically for the assessment of lipedema, the sample size estimation was based on data from a comparable lymphedema study. Using the G*Power 3.0.10a software, a power analysis was conducted. The effect size was calculated as 0.68, and with an alpha error probability of 5% (α = 0.05) and a power (1–β) of 95%, the minimum required sample size was determined to be 17 patients with lipedema ( 25 ). The study involved thirty-five women diagnosed with lipedema, aged between 18 and 65 years. Each participant received a diagnosis of lipedema from a physiatrist. Exclusions from the study encompassed elderly individuals, children, pregnant women, those who had recently given birth, individuals in intensive care or unconscious, and persons with disabilities. Furthermore, individuals exhibiting venous insufficiency with subcutaneous changes categorized as C3 to C6, those presenting with medical conditions or diseases that could result in edema (such as congestive heart failure, renal failure, or hypothyroidism), as well as individuals who opted not to participate, were also excluded from the study. Demographic and clinical characteristics were systematically recorded, encompassing age, weight, body mass index, education level, employment status, type of lipedema, and stage of lipedema. The severity of pain was evaluated using a visual analog scale (VAS). This scale ranges from 0 to 10, with 0 indicating no pain and 10 indicating the highest level of pain. The PainDetect questionnaire (PDQ) was utilized to evaluate neuropathic pain. PDQ has both a sensitivity and specificity of 84% and is routinely used in clinical care to screen patients for neuropathic pain. According to the PDQ-score, patient-reported pain is classified into three groups: a score < 13 indicates that the presence of a neuropathic pain component is unlikely (“unlikely neuropathic” or UNP), a score of 13–18 that it is indecisive (classified as “possible neuropathic” or PNP), while a score > 18 indicates that presence of a neuropathic pain component is likely (“likely neuropathic” or LNP) ( 26 ). Ultrasonographic measurements were performed using a linear transducer (Logiq P9, GE Medical Systems, USA, 6 to 15 MHz). Tissue elasticity and fibrosis were assessed utilizing shear wave elastography (SWE). Measurements of subcutaneous tissue thickness and SWE were conducted by a physician specializing in physical medicine and rehabilitation, who possesses a decade of experience in musculoskeletal ultrasonography. These evaluations were performed by preference of two predetermined anatomical sites specified and suggested in the literature, including the midpoint between the superior anterior iliac crest (thigh) and the inferior patellar border and the level of the superior part of femoral medial condyle (medial knee) ( 5 ) (Fig. 1 ). During the procedure, patients were placed in a comfortable, supine position to minimize muscle tension. The probe was gently positioned perpendicular to the skin over the target tissue, and three consecutive measurements were obtained at each site. The mean value was calculated and noted. Subcutaneous fat tissue distance, SWE-Elasticity (SWE-E) and SWE-Velocity (SWE-V) measurements were recorded. Statistical analysis was conducted utilizing IBM SPSS version 23.0 software (IBM Corp., Armonk, NY, USA). Descriptive statistics for continuous variables were reported as mean ± standard deviation (SD) or median and interquartile ranges, while categorical variables were expressed as numbers and percentages. Normal distribution was evaluated by histogram, detrended normal, and Q-Q plot visualizations and coefficient of variation, skewness and kurtosis analyses, and the Shapiro-Wilk test statistical analyses. Pearson’s correlation was used for parametric data, and Spearman’s correlation was used for nonparametric data to determine the association between variables. A p-value of < 0.05 was considered statistically significant. Results Thirty-five patients were analyzed in this study. The average age was 45.2±12.6 years, and the average VKI was 33.6 ± 5.5 (min: 24.0, max: 49.2) kg/m 2 . 21 of 35 patients (60%) had a lipedema diagnosis in their family history. Of the 21 patients, 12 had lipedema in their maternal relatives, 5 had lipedema in their paternal relatives, and 4 had lipedema in both their maternal and paternal relatives. The demographic data of the patients, including their educational status, occupation, lipedema stage, and type, are presented in Table 1 . The average VAS pain score is 5, with an interquartile range of 7. Additionally, 14.3% of patients report neuropathic pain according to PDQ scores. The mean ultrasonographic measurement values are provided in Table 2 . Table 1 Demographic and clinical characteristics of patients Age (years) Mean ± SD (min-max) 45.2 ± 12.6 (23–65) BMI (Kg/m 2 ) Mean ± SD (min-max) 33.6 ± 5.5 (24.0-49.2) Lipedema history of family 60% (n = 21) Education status (primary education and before) 37.7% (n = 13) Employment status (non-working) 54.3% (n = 19) Lipedema Type Type 2: 40% (n = 14) Type 3: 34.3% (n = 12) Type 4: 25.7% (n = 9) Lipedema Stage Stage 1: 8.6% (n = 3) Stage 2: 62.9% (n = 22) Stage 3: 28.6% (n = 10) VAS (cm) Median (IQR) 5 ( 7 ) PainDetect Median (IQR) 7 ( 14 ) PainDetect (neuropathic) 14.3% ( 5 ) Table 2 Ultrasonographic measurements of patients R L Thigh thickness Mean ± SD (min-max) 3.1 ± 0.8 (1.5–5.6) 3 ± 0.9 (1.4–5.6) Medial femoral condyle thickness Mean ± SD (min-max) 4 ± 0.9 (2.1–6.6) 3.9 ± 0.9 (2.2–6.6) Thigh SWE-V Mean ± SD (min-max) 1.8 ± 0.5 (1.2–2.9) 1.8 ± 0.5 (1.0–3.0) Thigh SWE-E Mean ± SD (min-max) 10.7 ± 5.0 (4.3–23.3) 10.3 ± 4.7 (4.0-24.6) Medial knee SWE-V Mean ± SD (min-max) 1.8 ± 0.4 (1.1–2.7) 1.9 ± 0.4 (1.1-3.0) Medial knee SWE-E Mean ± SD (min-max) 10.0 ± 4.2 (2.9–20.9) 9.8 ± 4.1 (2.7–20.7) In Table 3 , the correlations between age, BMI, and USG measurements are presented. Both age (p < 0.01) and BMI (p < 0.001) values were found to be moderately correlated with all subcutaneous adipose tissue measurements, whereas no correlation was found in SWE measurements. Table 3 Correlation analysis of data between age, BMI and ultrasonography measurements Age (years) BMI(kg/m 2 ) r 2 p r 2 p Body Mass Index (kg/m 2 ) 0.59 < 0.001 Thigh thickness R 0.43 0.009 0.69 < 0.001 Thigh thickness L 0.37 0.001 0.65 < 0.001 Medial femoral condyle thickness R 0.53 0.001 0.77 < 0.001 Medial femoral condyle thickness L 0.46 0.005 0.69 < 0.001 Thigh SWE-V R 0.06 0.71 0.17 0.31 Thigh SWE-E R 0.11 0.52 0.29 0.09 Thigh SWE-V L 0.21 0.90 0.07 0.65 Thigh SWE-E L 0.04 0.80 0.24 0.15 Medial knee SWE-V R -0.11 0.51 -0.21 0.21 Medial knee SWE-E R -0.17 0.31 -0.17 0.30 Medial knee SWE-V L -0.11 0.52 -0.11 0.51 Medial knee SWE-E L -0.19 0.25 -0.20 0.23 Pearson Corelation The correlation of pain and neuropathic pain data is detailed in Table 4 . Only the level of the thigh in the SWE-E values was found to be significantly related to VAS (p = 0.03). Moreover, more correlations were found in the painDetect data (weak correlation with SWE-V and SWE-E of the right and left thigh). Table 4 Correlation analysis of data between pain parameters and ultrasonography measurements VAS (cm) PainDetect Last question of PainDetect rho p rho p rho p Body Mass Index (kg/m 2 ) 0.06 0.71 0.19 0.26 0.04 0.81 Thigh thickness R 0.25 0.88 0.06 0.72 0.01 0.94 Thigh thickness L -0.06 0.71 -0.05 0.77 -0.07 0.65 Medial knee thickness R -0.05 0.78 0.01 0.91 -0.09 0.57 Medial knee thickness L -0.07 0.65 -0.06 0.69 -0.14 0.39 Thigh SWE-V R 0.22 0.19 0.38 0.02 0.40 0.01 Thigh SWE-E R 0.35 0.03 0.44 0.007 0.45 0.006 Thigh SWE-V L 0.23 0.17 0.47 0.004 0.44 0.008 Thigh SWE-E L 0.36 0.03 0.44 0.008 0.45 0.007 Medial knee SWE-V R 0.11 0.51 0.11 0.49 0.21 0.21 Medial knee SWE-E R -0.16 0.34 -0.04 0.79 0.02 0.89 Medial knee SWE-V L 0.09 0.58 0.04 0.77 0.06 0.73 Medial knee SWE-E L -0.09 0.57 0.01 0.93 0.05 0.74 Spearmen Corelation Discussion To our knowledge, this is the first study in the literature to utilize Shear Wave Elastography (SWE) for evaluating subcutaneous adipose tissue specifically in patients with lipedema. Unlike previous research, we uniquely explored the relationship between tissue elasticity and both general and neuropathic pain. Our findings reveal a significant correlation between SWE measurements in the thigh region and the severity of pain symptoms, highlighting the potential of SWE as a valuable tool for understanding and assessing pain mechanisms in lipedema. Several pathophysiological dysregulations have been reported in lipedema, including impaired adipogenesis and angiogenesis, increased fibrosis and hypoxia, as well as chronic inflammation and immune cell infiltration ( 27 ). A US consensus report highlighted excessive and fibrotic loose connective tissue and an increased presence of M2 macrophages in women with lipedema, alongside inflammatory angiogenesis and microangiopathy affecting both blood and lymphatic vessels, all of which may contribute to pain and disease progression ( 7 ). Nankam et al. demonstrated elevated levels of inflammatory proteins and oxidative stress markers, suggesting active inflammation in subcutaneous fat ( 27 ). Similarly, Felmerer et al. reported increased VEGF-C levels and macrophage infiltration despite normal lymphatic vessel morphology ( 28 ). Al-Ghadban et al. identified hypertrophic adipocytes, increased vascularity, and dilated capillaries in thigh tissue, supporting inflammatory processes ( 29 ). Ernst et al. confirmed upregulated fibrotic and inflammatory gene expression in lipedema adipocytes ( 30 ). Kruppa et al. found heightened macrophage gene expression and transient polarization towards an M2-like phenotype ( 31 ). Macrophages are key mediators of pain, and recent work by Von Atzigen et al. demonstrated that unlike lipedema and secondary lymphedema, lipohypertrophy shows neither increased immune cell infiltration nor pain, underscoring the role of inflammation and macrophages in lipedema-related pain ( 10 ). Similarly, the primary clinical feature that differentiates lipedema from obesity is the presence of pain, often referred to as "painful fat." This pain, along with increased tissue fibrosis, is believed to result from heightened inflammation within the lipedema-affected tissue. ( 27 ). Additionally, Von Atzigen et al. identified that the expansion of adipose tissue is associated with the remodeling of the extracellular matrix and the presence of fibrosis in individuals with lipedema. They found that secondary lymphedema results in increased fibrosis solely within adipose tissue, whereas lipedema demonstrates a notable tendency toward higher levels of adipose tissue fibrosis, yet this finding does not reach statistical significance ( 10 ). Streubel et al. conducted a comprehensive whole transcriptome analysis of subcutaneous fatty tissue from patients diagnosed with lipedema, comparing it to hypertrophied fatty tissue. The study identified 137 differentially expressed genes that play a role in the mechanisms contributing to the development of lipedema. In the same study, it was observed that Lumican (LUM), EMILIN2, and FBN1 demonstrate increased expression in lipedema, which contributes to the altered dynamics of the extracellular matrix. The degradation of the extracellular matrix, accompanied by resultant tissue fibrosis, reinitiates the inflammatory process, leading to tissue swelling and discomfort ( 32 ). Kruppa et al. found a notable increase in fibrotic tissue in the thighs of individuals with lipedema when comparing thigh biopsy histology to that of healthy controls. Moreover, they marked that subcutaneous adipose tissue was associated with increased interstitial collagen accumulation and a trend toward adipose tissue fibrosis in the affected thighs as the stage of lipedema progressed. Their findings revealed that pathological changes in the thigh's extracellular matrix commence early in the disease, at stage I, and occur before the hypertrophy of adipocytes. ( 31 ) Similarly, Ernst et al. reported increased collagen deposition in histological evaluations of subcutaneous adipose tissue biopsies from patients with lipedema, compared to a control group. They identified the upregulation of platelet-derived growth factor receptor-alpha mRNA levels in the context of lipedema-associated fibrosis ( 30 ). In light of the aforementioned information, lipedema is a multifactorial condition characterized by alterations in adipogenesis, inflammatory processes, fibrosis, and nociceptive responses. It is essential to give careful consideration to the roles of fibrosis and pain within this context. Ultrasound examination is a crucial tool for identifying the location and extent of fat accumulation, aiding in the differentiation of lipedema from other conditions, and enabling effective monitoring of treatment outcomes. Previous ultrasound examinations have demonstrated an increase in skin thickness and a reduction in echogenicity within the subcutaneous tissue in lipedema. Furthermore, a variety of ultrasonographic techniques, including real-time high-resolution cutaneous ultrasonography, cutaneous ultrasound in conjunction with computer-assisted measurement technology, color Doppler flow imaging, and ultra-micro angiography, have been employed in prior studies ( 5 , 9 , 33 – 36 ). Ultrasound elastography technology allows for the non-invasive evaluation of tissue stiffness by assessing changes in the elasticity of soft tissues. This technology offers valuable quantitative data for medical assessments. This research represents the initial investigation in existing literature that assesses subcutaneous tissue using shear wave elastography in individuals diagnosed with lipedema. Amato et al. established specific cutoff values for measuring regional thickness in the diagnosis of lipedema. These values include 11.7 mm for the pre-tibial region, 17.9 mm for the thigh, and 8.4 mm for the lateral leg ( 5 ). In our study, we observed that the average of regional thickness measurement surpassed the established cutoff value. We conducted an investigation into tissue elasticity and fibrosis utilizing the SWE method for the first time in the literature concerning patients diagnosed with lipedema. Additionally, we explored the relationship between pain—a factor that profoundly affects quality of life—and tissue elasticity. The SWE-E values at the thigh level were significantly correlated with the VAS (p = 0.03). Additionally, the painDetect data revealed correlations with both SWE-V and SWE-E for the right and left thigh. Our research contributes to the understanding of the relationship between pain, especially neuropathic pain, and tissue elasticity assessed via ultrasound elastography. Additionally, it offers valuable insights into the symptoms and pathophysiological changes associated with lipedema from a novel perspective. In addition to these evaluations, we analyzed the relationship between age, BMI and ultrasonographic data. Measurements of subcutaneous adipose tissue thickness were correlated with both age and BMI, while SWE measurements did not exhibit any correlation. On the other hand, statistical analyses revealed no relationship between BMI, scores of VAS and PDQ. These results align with the findings of Gensior and Cornely, who reported that pain levels related to lipedema are independent of BMI and not directly caused by inflammation ( 37 ). Moreover, our study revealed that the average pain score among participants was 5, which is slightly lower than the findings from Aitzetmüller-Klietz’s trial, where patients with lipedema reported an average pain score of 6.68 on a scale of 0 to 10 ( 12 ). A strength of our study is the objective assessment of tissue elasticity in lipedema, with a particular focus on evaluating its relationship with neuropathic pain. However, certain limitations should be acknowledged. Since there is no definitive objective biomarker for lipedema, diagnosis primarily relies on thorough clinical evaluation, making the accuracy of diagnosis closely dependent on the clinician’s expertise and familiarity with the condition. Conclusions In conclusion, lipedema is a complex and multifactorial disease characterized by disruptions in cell differentiation, adipogenesis, and proliferation, leading to inflammation, fibrosis, and pain. Timely and accurate diagnosis is essential for effective clinical management. 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Transcriptomics of Subcutaneous Tissue of Lipedema Identified Differentially Expressed Genes Involved in Adipogenesis, Inflammation, and Pain. Plast Reconstr Surg Glob Open. 2024 Nov 8;12(11):e6288. doi: 10.1097/GOX.0000000000006288. Marshall M and Schwahn-Schreiber C. Pr€avalenz des Lip€odems bei berufst€atigen Frauen in Deutschland. Phlebologie 2011; 40: 127–134. Iker E, Mayfield CK, Gould DJ, Patel KM. Characterizing Lower Extremity Lymphedema and Lipedema with Cutaneous Ultrasonography and an Objective Computer-Assisted Measurement of Dermal Echogenicity. Lymphat Res Biol. 2019 Oct;17(5):525-530. doi: 10.1089/lrb.2017.0090. Epub 2019 Jan 7. PMID: 30615553. Naouri M, Samimi M, Atlan M, Perrodeau E, Vallin C, Zakine G, et al. High-resolution cutaneous ultrasonography to differentiate lipoedema from lymphoedema. Br J Dermatol. 2010 Aug;163(2):296-301. doi: 10.1111/j.1365-2133.2010.09810.x. Kempa S, Tessmann V, Prantl L, Schmid S, Müller M, Jung EM, et al. The value of sonographic microvascular imaging in the diagnosis of lipedema. Clin Hemorheol Microcirc. 2024;86(1-2):99-108. doi: 10.3233/CH-238103. Gensior MHL, Cornely M. Der Lipödemschmerz, seine Folgen auf die Lebensqualität betroffener Patientinnen – Ergebnisse einer Patientenbefragung mittels Schmerzfragebogen [Pain in lipoedema, fat in lipoedema and its consequences: results of a patient survey based on a pain questionnaire]. Handchir Mikrochir Plast Chir. 2019 Aug;51(4):249-254. German. doi: 10.1055/a-0942-9607. Additional Declarations There is NO conflict of interest to disclose Cite Share Download PDF Status: Published Journal Publication published 14 Mar, 2026 Read the published version in International Journal of Obesity → Version 1 posted Editorial decision: revise 07 Nov, 2025 Review # 2 received at journal 22 Oct, 2025 Reviewer # 2 agreed at journal 02 Oct, 2025 Review # 1 received at journal 02 Sep, 2025 Reviewer # 1 agreed at journal 15 Aug, 2025 Reviewers invited by journal 10 Aug, 2025 Submission checks completed at journal 07 Jul, 2025 First submitted to journal 04 Jul, 2025 Unknown event 04 Jul, 2025 Editor assigned by journal 03 Jul, 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. 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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-7041394","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":498353249,"identity":"50f6a769-4f72-4a4d-ba45-9a718c5bb6df","order_by":0,"name":"Aysegul Yaman","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABEElEQVRIiWNgGAWjYPACCwiVUGEDJBkbDxChRQJCfTiTBtLSQLwWxpkth8EMvFr4Z6Q/fPi1TSKxf9rhZ495G87brW0/DLSlxiYap/E3coyNZYFaZtxOMzfm3XE7eduZRKCWY2m5Dbj03Mhhk5YEamm4nWAmzXvmdrLZAaAWxobDOLXI30h//hukZf7t9G/SvG3nks3OP8SvxeBGghnjR6CWDbdzzCRnth2wM7tBwBbDM2+MpRnOSRhvvJ1TJvHhTHKC2Q2gLQl4/CJ3PP3hxx9lNrLzbqdvk0iosLM3O5/+8MGHGhvc3hdIYGDmYWBwhClIBDMScCkHAf4DDIw/GBjsYXx7fIpHwSgYBaNgZAIA67driZASIrIAAAAASUVORK5CYII=","orcid":"","institution":"Ankara Etlik City Hospital","correspondingAuthor":true,"prefix":"","firstName":"Aysegul","middleName":"","lastName":"Yaman","suffix":""},{"id":498353250,"identity":"37e0ecc1-f9f7-42f4-9ed5-d104b7cfd5cb","order_by":1,"name":"Başak Kaplan","email":"","orcid":"","institution":"Ankara Etlik City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Başak","middleName":"","lastName":"Kaplan","suffix":""}],"badges":[],"createdAt":"2025-07-03 21:20:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7041394/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7041394/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41366-026-02049-8","type":"published","date":"2026-03-14T04:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":89288930,"identity":"fb8f757e-0d7c-445a-bb75-aa1cccab1e65","added_by":"auto","created_at":"2025-08-18 12:00:13","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":223745,"visible":true,"origin":"","legend":"\u003cp\u003eSites of ultrasonographic measurement: A: Thigh thickness (the midpoint between the superior anterior iliac crest) B: Medial knee thickness (the inferior patellar border and the level of the superior part of femoral medial condyle).\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7041394/v1/6f7e28ad480c5e48ffac01df.png"},{"id":104649783,"identity":"d3bdafc9-f02c-40a7-a416-a0586f3d7b4e","added_by":"auto","created_at":"2026-03-15 07:07:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":931025,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7041394/v1/636f119f-4159-410b-be6c-93d977ee2e43.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e conflict of interest to disclose","formattedTitle":"Assessment of the elasticity of lipedematous tissue and the examination of the relationship between pain and fibrosis in lipedema","fulltext":[{"header":"Introduction","content":"\u003cp\u003eLipedema is a chronic and progressive disorder of adipose tissue characterized by the abnormal accumulation of subcutaneous fat, predominantly in the legs and occasionally in the arms. Mainly affecting women, this condition is often misidentified as obesity or lymphedema. The underlying cause is poorly understood. The precise prevalence of lipedema within the general population remains unclear; however, studies indicate that the occurrence of a positive family history ranges from 16–64% (\u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5 CR6 CR7 CR8 CR9\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e–\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eLipedema is often recognized as emerging during crucial periods of hormonal change, especially during puberty, pregnancy, or menopause. Individuals diagnosed with lipedema frequently report experiencing discomfort, easy bruising, and tenderness in their enlarged legs. These symptoms may progress to severe pain and may result in restricted mobility. In addition to physical complications, lipedema can also cause psychological distress. (\u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5 CR6\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e–\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan additionalcitationids=\"CR10 CR11 CR12 CR13 CR14 CR15 CR16 CR17\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e–\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe symptom that most profoundly impacts daily life is pain. The precise causes of pain associated with lipedema are still not fully understood. Excess fat accumulation in specific body regions triggers low-grade chronic inflammation, disrupting adipocyte metabolism. This disruption leads to increased oxidative damage to lipids and localized hypoxia (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Sympathetic and sensory nerves innervate subcutaneous adipose tissue, while adipocytes synthesize and secrete neurotrophic factors that modulate sensory innervation. (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e) Estrogen may play a critical role in the sympathetic nervous system's innervation of subcutaneous adipose tissue, potentially leading to innervation abnormalities and sensory nerve inflammation. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). The Neuropathic Pain Special Interest Group (NeuPSIG) of the International Association for the Study of Pain (IASP) defines neuropathic pain as \"pain resulting directly from a lesion or disease that affects the somatosensory system.\"(\u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e–\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). Individuals with lipedema frequently experience pain in the affected areas that is both allodynic and neuropathic in nature (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). There is still a limited understanding of the factors associated with pain in lipedema. Recognizing and comprehending the elements contributing to pain linked with lipedema may assist in precisely evaluating the severity of the condition.\u003c/p\u003e\u003cp\u003eLipedema is characterized by an increase in skin thickness and a reduction in echogenicity within the subcutaneous tissue. High-frequency ultrasound imaging is an effective tool for visualizing subcutaneous adipose tissue. It enables a comprehensive assessment of the thickness and characteristics of fat layers, thereby facilitating a better understanding of tissue composition (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Ultrasound elastography is an imaging technology that allows for the quantitative measurement of tissue stiffness (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThis study aimed to investigate the relationship between accompanying pain in patients with lipedema and tissue elasticity, as measured using shear-wave elastography (SWE).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eA cross-sectional, observational, and analytical study was conducted in the outpatient clinic of Ankara Etlik City Hospital's Clinic of Physical Medicine and Rehabilitation between June and December 2024. Approval for the study was granted by the local ethical committee (AESH-BADEK-2024-395). The study was conducted in accordance with the principles of the Declaration of Helsinki. A written informed consent was obtained from each patient.\u003c/p\u003e\u003cp\u003eDue to the lack of previous studies employing elastography specifically for the assessment of lipedema, the sample size estimation was based on data from a comparable lymphedema study. Using the G*Power 3.0.10a software, a power analysis was conducted. The effect size was calculated as 0.68, and with an alpha error probability of 5% (α = 0.05) and a power (1–β) of 95%, the minimum required sample size was determined to be 17 patients with lipedema (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe study involved thirty-five women diagnosed with lipedema, aged between 18 and 65 years. Each participant received a diagnosis of lipedema from a physiatrist. Exclusions from the study encompassed elderly individuals, children, pregnant women, those who had recently given birth, individuals in intensive care or unconscious, and persons with disabilities. Furthermore, individuals exhibiting venous insufficiency with subcutaneous changes categorized as C3 to C6, those presenting with medical conditions or diseases that could result in edema (such as congestive heart failure, renal failure, or hypothyroidism), as well as individuals who opted not to participate, were also excluded from the study.\u003c/p\u003e\u003cp\u003eDemographic and clinical characteristics were systematically recorded, encompassing age, weight, body mass index, education level, employment status, type of lipedema, and stage of lipedema.\u003c/p\u003e\u003cp\u003eThe severity of pain was evaluated using a visual analog scale (VAS). This scale ranges from 0 to 10, with 0 indicating no pain and 10 indicating the highest level of pain.\u003c/p\u003e\u003cp\u003eThe PainDetect questionnaire (PDQ) was utilized to evaluate neuropathic pain. PDQ has both a sensitivity and specificity of 84% and is routinely used in clinical care to screen patients for neuropathic pain. According to the PDQ-score, patient-reported pain is classified into three groups: a score \u0026lt; 13 indicates that the presence of a neuropathic pain component is unlikely (“unlikely neuropathic” or UNP), a score of 13–18 that it is indecisive (classified as “possible neuropathic” or PNP), while a score \u0026gt; 18 indicates that presence of a neuropathic pain component is likely (“likely neuropathic” or LNP) (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eUltrasonographic measurements were performed using a linear transducer (Logiq P9, GE Medical Systems, USA, 6 to 15 MHz). Tissue elasticity and fibrosis were assessed utilizing shear wave elastography (SWE). Measurements of subcutaneous tissue thickness and SWE were conducted by a physician specializing in physical medicine and rehabilitation, who possesses a decade of experience in musculoskeletal ultrasonography. These evaluations were performed by preference of two predetermined anatomical sites specified and suggested in the literature, including the midpoint between the superior anterior iliac crest (thigh) and the inferior patellar border and the level of the superior part of femoral medial condyle (medial knee) (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). During the procedure, patients were placed in a comfortable, supine position to minimize muscle tension. The probe was gently positioned perpendicular to the skin over the target tissue, and three consecutive measurements were obtained at each site. The mean value was calculated and noted. Subcutaneous fat tissue distance, SWE-Elasticity (SWE-E) and SWE-Velocity (SWE-V) measurements were recorded.\u003c/p\u003e\u003cp\u003eStatistical analysis was conducted utilizing IBM SPSS version 23.0 software (IBM Corp., Armonk, NY, USA). Descriptive statistics for continuous variables were reported as mean ± standard deviation (SD) or median and interquartile ranges, while categorical variables were expressed as numbers and percentages. Normal distribution was evaluated by histogram, detrended normal, and Q-Q plot visualizations and coefficient of variation, skewness and kurtosis analyses, and the Shapiro-Wilk test statistical analyses. Pearson’s correlation was used for parametric data, and Spearman’s correlation was used for nonparametric data to determine the association between variables. A p-value of \u0026lt; 0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThirty-five patients were analyzed in this study. The average age was 45.2\u0026plusmn;12.6 years, and the average VKI was 33.6 \u0026plusmn; 5.5 (min: 24.0, max: 49.2) kg/m\u003csup\u003e2\u003c/sup\u003e. 21 of 35 patients (60%) had a lipedema diagnosis in their family history. Of the 21 patients, 12 had lipedema in their maternal relatives, 5 had lipedema in their paternal relatives, and 4 had lipedema in both their maternal and paternal relatives. The demographic data of the patients, including their educational status, occupation, lipedema stage, and type, are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The average VAS pain score is 5, with an interquartile range of 7. Additionally, 14.3% of patients report neuropathic pain according to PDQ scores. The mean ultrasonographic measurement values are provided in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\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\u003eDemographic and clinical characteristics of patients\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\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\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (years)\u003c/p\u003e\u003cp\u003eMean \u0026plusmn; SD (min-max)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e45.2 \u0026plusmn; 12.6 (23\u0026ndash;65)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBMI (Kg/m\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eMean \u0026plusmn; SD (min-max)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e33.6 \u0026plusmn; 5.5 (24.0-49.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLipedema history of family\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e60% (n\u0026thinsp;=\u0026thinsp;21)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eEducation status\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(primary education and before)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e37.7% (n\u0026thinsp;=\u0026thinsp;13)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eEmployment status\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(non-working)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e54.3% (n\u0026thinsp;=\u0026thinsp;19)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLipedema Type\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eType 2: 40% (n\u0026thinsp;=\u0026thinsp;14)\u003c/p\u003e\u003cp\u003eType 3: 34.3% (n\u0026thinsp;=\u0026thinsp;12)\u003c/p\u003e\u003cp\u003eType 4: 25.7% (n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLipedema Stage\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eStage 1: 8.6% (n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e\u003cp\u003eStage 2: 62.9% (n\u0026thinsp;=\u0026thinsp;22)\u003c/p\u003e\u003cp\u003eStage 3: 28.6% (n\u0026thinsp;=\u0026thinsp;10)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eVAS (cm)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eMedian (IQR)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePainDetect\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eMedian (IQR)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePainDetect\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(neuropathic)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14.3% (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\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\u003eUltrasonographic measurements of patients\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\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\u003eR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eL\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eThigh thickness\u003c/p\u003e\u003cp\u003eMean \u0026plusmn; SD (min-max)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e3.1 \u0026plusmn; 0.8 (1.5\u0026ndash;5.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e3 \u0026plusmn; 0.9 (1.4\u0026ndash;5.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedial femoral condyle thickness\u003c/p\u003e\u003cp\u003eMean \u0026plusmn; SD (min-max)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e4 \u0026plusmn; 0.9 (2.1\u0026ndash;6.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e3.9 \u0026plusmn; 0.9 (2.2\u0026ndash;6.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eThigh SWE-V\u003c/p\u003e\u003cp\u003eMean \u0026plusmn; SD (min-max)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e1.8 \u0026plusmn; 0.5 (1.2\u0026ndash;2.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e1.8 \u0026plusmn; 0.5 (1.0\u0026ndash;3.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eThigh SWE-E\u003c/p\u003e\u003cp\u003eMean \u0026plusmn; SD (min-max)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e10.7 \u0026plusmn; 5.0 (4.3\u0026ndash;23.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e10.3 \u0026plusmn; 4.7 (4.0-24.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedial knee SWE-V\u003c/p\u003e\u003cp\u003eMean \u0026plusmn; SD (min-max)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e1.8 \u0026plusmn; 0.4 (1.1\u0026ndash;2.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e1.9 \u0026plusmn; 0.4 (1.1-3.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedial knee SWE-E\u003c/p\u003e\u003cp\u003eMean \u0026plusmn; SD (min-max)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e10.0 \u0026plusmn; 4.2 (2.9\u0026ndash;20.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e9.8 \u0026plusmn; 4.1 (2.7\u0026ndash;20.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eIn Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, the correlations between age, BMI, and USG measurements are presented. Both age (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) and BMI (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) values were found to be moderately correlated with all subcutaneous adipose tissue measurements, whereas no correlation was found in SWE measurements.\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\u003eCorrelation analysis of data between age, BMI and ultrasonography measurements\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eAge (years)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003eBMI(kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003er\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003er\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eBody Mass Index (kg/m\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u003cem\u003e)\u003c/em\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=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eThigh thickness R\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e0.43\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e0.009\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.69\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\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\u003e\u003cem\u003eThigh thickness L\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e0.37\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.65\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\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\u003e\u003cem\u003eMedial femoral condyle thickness R\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e0.53\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.77\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\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\u003e\u003cem\u003eMedial femoral condyle thickness L\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e0.46\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e0.005\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.69\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\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\u003e\u003cem\u003eThigh SWE-V R\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.71\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.31\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eThigh SWE-E R\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.52\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.09\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eThigh SWE-V L\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.90\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.65\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eThigh SWE-E L\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.15\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eMedial knee SWE-V R\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.21\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eMedial knee SWE-E R\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.30\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eMedial knee SWE-V L\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.52\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.51\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eMedial knee SWE-E L\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.23\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003ePearson Corelation\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe correlation of pain and neuropathic pain data is detailed in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. Only the level of the thigh in the SWE-E values was found to be significantly related to VAS (p\u0026thinsp;=\u0026thinsp;0.03). Moreover, more correlations were found in the painDetect data (weak correlation with SWE-V and SWE-E of the right and left thigh).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCorrelation analysis of data between pain parameters and ultrasonography measurements\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eVAS (cm)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003ePainDetect\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u003cp\u003eLast question of PainDetect\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003erho\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003erho\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003erho\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eBody Mass Index (kg/m\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u003cem\u003e)\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.71\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.81\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eThigh thickness R\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.88\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.72\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.94\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eThigh thickness L\u003c/em\u003e\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=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.71\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-0.05\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.77\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e-0.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.65\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eMedial knee thickness R\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.05\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.78\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.91\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e-0.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.57\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eMedial knee thickness L\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.65\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-0.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.69\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e-0.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.39\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eThigh SWE-V R\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.38\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.02\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e0.40\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e0.01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eThigh SWE-E R\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e0.35\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e0.03\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.44\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.007\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e0.45\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e0.006\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eThigh SWE-V L\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.47\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.004\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e0.44\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e0.008\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eThigh SWE-E L\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e0.36\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e0.03\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.44\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.008\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e0.45\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e0.007\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eMedial knee SWE-V R\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.21\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eMedial knee SWE-E R\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-0.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.79\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.02\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.89\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eMedial knee SWE-V L\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.77\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.73\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eMedial knee SWE-E L\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.57\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.93\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.05\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.74\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003eSpearmen Corelation\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo our knowledge, this is the first study in the literature to utilize Shear Wave Elastography (SWE) for evaluating subcutaneous adipose tissue specifically in patients with lipedema. Unlike previous research, we uniquely explored the relationship between tissue elasticity and both general and neuropathic pain. Our findings reveal a significant correlation between SWE measurements in the thigh region and the severity of pain symptoms, highlighting the potential of SWE as a valuable tool for understanding and assessing pain mechanisms in lipedema.\u003c/p\u003e\u003cp\u003eSeveral pathophysiological dysregulations have been reported in lipedema, including impaired adipogenesis and angiogenesis, increased fibrosis and hypoxia, as well as chronic inflammation and immune cell infiltration (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). A US consensus report highlighted excessive and fibrotic loose connective tissue and an increased presence of M2 macrophages in women with lipedema, alongside inflammatory angiogenesis and microangiopathy affecting both blood and lymphatic vessels, all of which may contribute to pain and disease progression (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Nankam et al. demonstrated elevated levels of inflammatory proteins and oxidative stress markers, suggesting active inflammation in subcutaneous fat (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Similarly, Felmerer et al. reported increased VEGF-C levels and macrophage infiltration despite normal lymphatic vessel morphology (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Al-Ghadban et al. identified hypertrophic adipocytes, increased vascularity, and dilated capillaries in thigh tissue, supporting inflammatory processes (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). Ernst et al. confirmed upregulated fibrotic and inflammatory gene expression in lipedema adipocytes (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). Kruppa et al. found heightened macrophage gene expression and transient polarization towards an M2-like phenotype (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). Macrophages are key mediators of pain, and recent work by Von Atzigen et al. demonstrated that unlike lipedema and secondary lymphedema, lipohypertrophy shows neither increased immune cell infiltration nor pain, underscoring the role of inflammation and macrophages in lipedema-related pain (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Similarly, the primary clinical feature that differentiates lipedema from obesity is the presence of pain, often referred to as \"painful fat.\" This pain, along with increased tissue fibrosis, is believed to result from heightened inflammation within the lipedema-affected tissue. (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Additionally, Von Atzigen et al. identified that the expansion of adipose tissue is associated with the remodeling of the extracellular matrix and the presence of fibrosis in individuals with lipedema. They found that secondary lymphedema results in increased fibrosis solely within adipose tissue, whereas lipedema demonstrates a notable tendency toward higher levels of adipose tissue fibrosis, yet this finding does not reach statistical significance (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Streubel et al. conducted a comprehensive whole transcriptome analysis of subcutaneous fatty tissue from patients diagnosed with lipedema, comparing it to hypertrophied fatty tissue. The study identified 137 differentially expressed genes that play a role in the mechanisms contributing to the development of lipedema. In the same study, it was observed that Lumican (LUM), EMILIN2, and FBN1 demonstrate increased expression in lipedema, which contributes to the altered dynamics of the extracellular matrix. The degradation of the extracellular matrix, accompanied by resultant tissue fibrosis, reinitiates the inflammatory process, leading to tissue swelling and discomfort (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). Kruppa et al. found a notable increase in fibrotic tissue in the thighs of individuals with lipedema when comparing thigh biopsy histology to that of healthy controls. Moreover, they marked that subcutaneous adipose tissue was associated with increased interstitial collagen accumulation and a trend toward adipose tissue fibrosis in the affected thighs as the stage of lipedema progressed. Their findings revealed that pathological changes in the thigh's extracellular matrix commence early in the disease, at stage I, and occur before the hypertrophy of adipocytes. (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e) Similarly, Ernst et al. reported increased collagen deposition in histological evaluations of subcutaneous adipose tissue biopsies from patients with lipedema, compared to a control group. They identified the upregulation of platelet-derived growth factor receptor-alpha mRNA levels in the context of lipedema-associated fibrosis (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIn light of the aforementioned information, lipedema is a multifactorial condition characterized by alterations in adipogenesis, inflammatory processes, fibrosis, and nociceptive responses. It is essential to give careful consideration to the roles of fibrosis and pain within this context.\u003c/p\u003e\u003cp\u003eUltrasound examination is a crucial tool for identifying the location and extent of fat accumulation, aiding in the differentiation of lipedema from other conditions, and enabling effective monitoring of treatment outcomes. Previous ultrasound examinations have demonstrated an increase in skin thickness and a reduction in echogenicity within the subcutaneous tissue in lipedema. Furthermore, a variety of ultrasonographic techniques, including real-time high-resolution cutaneous ultrasonography, cutaneous ultrasound in conjunction with computer-assisted measurement technology, color Doppler flow imaging, and ultra-micro angiography, have been employed in prior studies (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan additionalcitationids=\"CR34 CR35\" citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e). Ultrasound elastography technology allows for the non-invasive evaluation of tissue stiffness by assessing changes in the elasticity of soft tissues. This technology offers valuable quantitative data for medical assessments. This research represents the initial investigation in existing literature that assesses subcutaneous tissue using shear wave elastography in individuals diagnosed with lipedema.\u003c/p\u003e\u003cp\u003eAmato et al. established specific cutoff values for measuring regional thickness in the diagnosis of lipedema. These values include 11.7 mm for the pre-tibial region, 17.9 mm for the thigh, and 8.4 mm for the lateral leg (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). In our study, we observed that the average of regional thickness measurement surpassed the established cutoff value.\u003c/p\u003e\u003cp\u003eWe conducted an investigation into tissue elasticity and fibrosis utilizing the SWE method for the first time in the literature concerning patients diagnosed with lipedema. Additionally, we explored the relationship between pain\u0026mdash;a factor that profoundly affects quality of life\u0026mdash;and tissue elasticity. The SWE-E values at the thigh level were significantly correlated with the VAS (p\u0026thinsp;=\u0026thinsp;0.03). Additionally, the painDetect data revealed correlations with both SWE-V and SWE-E for the right and left thigh. Our research contributes to the understanding of the relationship between pain, especially neuropathic pain, and tissue elasticity assessed via ultrasound elastography. Additionally, it offers valuable insights into the symptoms and pathophysiological changes associated with lipedema from a novel perspective. In addition to these evaluations, we analyzed the relationship between age, BMI and ultrasonographic data. Measurements of subcutaneous adipose tissue thickness were correlated with both age and BMI, while SWE measurements did not exhibit any correlation. On the other hand, statistical analyses revealed no relationship between BMI, scores of VAS and PDQ. These results align with the findings of Gensior and Cornely, who reported that pain levels related to lipedema are independent of BMI and not directly caused by inflammation (\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e). Moreover, our study revealed that the average pain score among participants was 5, which is slightly lower than the findings from Aitzetm\u0026uuml;ller-Klietz\u0026rsquo;s trial, where patients with lipedema reported an average pain score of 6.68 on a scale of 0 to 10 (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eA strength of our study is the objective assessment of tissue elasticity in lipedema, with a particular focus on evaluating its relationship with neuropathic pain. However, certain limitations should be acknowledged. Since there is no definitive objective biomarker for lipedema, diagnosis primarily relies on thorough clinical evaluation, making the accuracy of diagnosis closely dependent on the clinician\u0026rsquo;s expertise and familiarity with the condition.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn conclusion, lipedema is a complex and multifactorial disease characterized by disruptions in cell differentiation, adipogenesis, and proliferation, leading to inflammation, fibrosis, and pain. Timely and accurate diagnosis is essential for effective clinical management. Ultrasound elastography, as a quantitative method for assessing tissue stiffness, may support early diagnosis. Our findings suggest a potential association between tissue elasticity and pain, highlighting the need for further research. A deeper understanding of neuropathic pain in lipedema could improve both diagnostic precision and therapeutic approaches.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAcknowledgement: None\u003c/p\u003e\n\u003cp\u003eConflict of Interest: None\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eLangendoen SI, Habbema L, Nijsten TE, Neumann HA. Lipoedema: from clinical presentation to therapy. A review of the literature. Br J Dermatol. 2009 Nov;161(5):980-6. doi: 10.1111/j.1365-2133.2009.09413.x.\u003c/li\u003e\n \u003cli\u003eWollina U. Lipedema-An update. Dermatol Ther. 2019 Mar;32(2):e12805. doi: 10.1111/dth.12805.\u003c/li\u003e\n \u003cli\u003eBauer AT, von Lukowicz D, Lossagk K, Aitzetmueller M, Moog P, Cerny M, et al. New Insights on Lipedema: The Enigmatic Disease of the Peripheral Fat. Plast Reconstr Surg. 2019 Dec;144(6):1475-1484. doi: 10.1097/PRS.0000000000006280.\u003c/li\u003e\n \u003cli\u003eTodd M. 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Qual Life Res. 2023 Jan;32(1):127-137. doi: 10.1007/s11136-022-03216-w. Epub 2022 Aug 16.\u003c/li\u003e\n \u003cli\u003ehttps://www.iasp-pain.org/resources/terminology/#pain\u003c/li\u003e\n \u003cli\u003eJensen TS, Baron R, Haanp\u0026auml;\u0026auml; M, Kalso E, Loeser JD, Rice AS, et al. A new definition of neuropathic pain. Pain. 2011 Oct;152(10):2204-5. doi:10.1016/j.pain.2011.06.017. Epub 2011 Jul 18.\u003c/li\u003e\n \u003cli\u003eTreede RD, Jensen TS, Campbell JN, Cruccu G, Dostrovsky JO, Griffin JW, et al. Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology. 2008 Apr 29;70(18):1630-5. doi: 10.1212/01.wnl.0000282763.29778.59. Epub 2007 Nov 14. PMID: 18003941.\u003c/li\u003e\n \u003cli\u003eChakraborty A, Crescenzi R, Usman TA, Reyna AJ, Garza ME, Al-Ghadban S, et al. Indications of Peripheral Pain, Dermal Hypersensitivity, and Neurogenic Inflammation in Patients with Lipedema. Int J Mol Sci. 2022 Sep 7;23(18):10313. doi: 10.3390/ijms231810313.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eSigrist RMS, Liau J, Kaffas AE, Chammas MC, Willmann JK. Ultrasound Elastography: Review of Techniques and Clinical Applications. Theranostics. 2017 Mar 7;7(5):1303-1329. doi: 10.7150/thno.18650.\u003c/li\u003e\n \u003cli\u003eBrandenburg JE, Eby SF, Song P, Zhao H, Brault JS, Chen S, et al. Ultrasound elastography: the new frontier in direct measurement of muscle stiffness. Arch Phys Med Rehabil. 2014 Nov;95(11):2207-19. doi: 10.1016/j.apmr.2014.07.007.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eErdogan Iyigun Z, Agacayak F, Ilgun AS, Elbuken Celebi F, Ordu C, Alco G, et al. The Role of Elastography in Diagnosis and Staging of Breast Cancer-Related Lymphedema. Lymphat Res Biol. 2019 Jun;17(3):334-339. doi: 10.1089/lrb.2018.0012.\u003c/li\u003e\n \u003cli\u003eAlkan H, Ardic F, Erdogan C, Sahin F, Sarsan A, Findikoglu G.Turkish version of the painDETECT questionnaire in the assessment of neuropathic pain: a validity and reliability study. Pain Med. 2013 Dec;14(12):1933-43. doi: 10.1111/pme.12222. Epub 2013 Aug 7.\u003c/li\u003e\n \u003cli\u003eNankam PAN, Cornely M, Kl\u0026ouml;ting N, Bl\u0026uuml;her M. Is subcutaneous adipose tissue expansion in people living with lipedema healthier and reflected by circulating parameters? Front Endocrinol (Lausanne). 2022 Oct 31;13:1000094. doi: 10.3389/fendo.2022.1000094.\u003c/li\u003e\n \u003cli\u003eFelmerer G, Stylianaki A, Hollm\u0026eacute;n M, Str\u0026ouml;bel P, Stepniewski A, Wang A, et al. Increased levels of VEGF-C and macrophage infiltration in lipedema patients without changes in lymphatic vascular morphology. Sci Rep. 2020 Jul 2;10(1):10947. doi: 10.1038/s41598-020-67987-3.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eAl-Ghadban S, Cromer W, Allen M, Ussery C, Badowski M, Harris D, et al. Dilated Blood and Lymphatic Microvessels, Angiogenesis, Increased Macrophages, and Adipocyte Hypertrophy in Lipedema Thigh Skin and Fat Tissue. J Obes. 2019 Mar 3;2019:8747461. doi: 10.1155/2019/8747461.\u003c/li\u003e\n \u003cli\u003eErnst AM, Schimak E, Steiner M, Lipp AT, Bauer HC, Bauer H. Lipedema Adipocytes in Culture: Signs of Hypertrophy, Inflammation, and Fibrosis [Internet]. Adipose Tissue Homeostasis in Health and Disease. IntechOpen; 2024. Available from: http://dx.doi.org/10.5772/intechopen.1004241\u003c/li\u003e\n \u003cli\u003eKruppa P, Gohlke S, Łapiński K, Garcia-Carrizo F, Soultoukis GA, Infanger M, et al. Lipedema stage affects adipocyte hypertrophy, subcutaneous adipose tissue inflammation and interstitial fibrosis. Front Immunol. 2023 Jul 28;14:1223264. doi: 10.3389/fimmu.2023.1223264.\u003c/li\u003e\n \u003cli\u003eStreubel MK, Baumgartner A, Meier-Vollrath I, Frambach Y, Brandenburger M, Kisch T. Transcriptomics of Subcutaneous Tissue of Lipedema Identified Differentially Expressed Genes Involved in Adipogenesis, Inflammation, and Pain. Plast Reconstr Surg Glob Open. 2024 Nov 8;12(11):e6288. doi: 10.1097/GOX.0000000000006288.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eMarshall M and Schwahn-Schreiber C. Pr\u0026euro;avalenz des Lip\u0026euro;odems bei berufst\u0026euro;atigen Frauen in Deutschland. Phlebologie 2011; 40: 127\u0026ndash;134.\u003c/li\u003e\n \u003cli\u003eIker E, Mayfield CK, Gould DJ, Patel KM. Characterizing Lower Extremity Lymphedema and Lipedema with Cutaneous Ultrasonography and an Objective Computer-Assisted Measurement of Dermal Echogenicity. Lymphat Res Biol. 2019 Oct;17(5):525-530. doi: 10.1089/lrb.2017.0090. Epub 2019 Jan 7. PMID: 30615553.\u003c/li\u003e\n \u003cli\u003eNaouri M, Samimi M, Atlan M, Perrodeau E, Vallin C, Zakine G, et al. High-resolution cutaneous ultrasonography to differentiate lipoedema from lymphoedema. Br J Dermatol. 2010 Aug;163(2):296-301. doi: 10.1111/j.1365-2133.2010.09810.x.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eKempa S, Tessmann V, Prantl L, Schmid S, M\u0026uuml;ller M, Jung EM, et al. The value of sonographic microvascular imaging in the diagnosis of lipedema. Clin Hemorheol Microcirc. 2024;86(1-2):99-108. doi: 10.3233/CH-238103.\u003c/li\u003e\n \u003cli\u003eGensior MHL, Cornely M. Der Lip\u0026ouml;demschmerz, seine Folgen auf die Lebensqualit\u0026auml;t betroffener Patientinnen \u0026ndash; Ergebnisse einer Patientenbefragung mittels Schmerzfragebogen [Pain in lipoedema, fat in lipoedema and its consequences: results of a patient survey based on a pain questionnaire]. Handchir Mikrochir Plast Chir. 2019 Aug;51(4):249-254. German. doi: 10.1055/a-0942-9607.\u0026nbsp;\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-obesity","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"ijo","sideBox":"Learn more about [International Journal of Obesity](http://www.nature.com/ijo/)","snPcode":"41366","submissionUrl":"https://mts-ijo.nature.com/cgi-bin/main.plex","title":"International Journal of Obesity","twitterHandle":"@intjobesity","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7041394/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7041394/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground/Objectives: \u003c/strong\u003eLipedema is a chronic and progressive adipose tissue disorder characterized by the abnormal accumulation of subcutaneous fat, predominantly in the legs and occasionally in the arms. The symptom that most significantly affects the quality of life is pain. Ultrasound elastography is an imaging technology that allows for measuring tissue stiffness quantitatively. This study aims to evaluate the relationship between accompanying pain in patients with lipedema and tissue elasticity measured using shear-wave elastography (SWE).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eOur study was designed as an observational, analytical and cross-sectional study. The visual analog scale (VAS) was used to assess pain, while the PainDetect questionnaire was utilized to evaluate neuropathic pain. The evaluation of tissue elasticity and fibrosis was conducted using the SWE method.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e This research assessed thirty-five patients, revealing an average age of 45.2 years and an average VKI of 33.6 kg/m². 60% of the patients had a lipedema diagnosis in their family history. Both age (p\u0026lt;0.01) and BMI (p\u0026lt;0.001) values were moderately correlated with all subcutaneous adipose tissue measurements, while no correlation was observed in SWE measurements. Only the level of the thigh in the SWE-Elasticity (SWE-E) values was related to VAS (p=0.03). Additionally, PainDetect data revealed correlations with SWE-Velocity (SWE-V) and SWE-E in both the right and left thighs.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e While SWE measurements were not correlated with skin adipose tissue, SWE measurements were correlated with pain and neuropathic pain in patients with lipedema. This finding highlights a potentially important relationship between tissue elasticity and pain, which may warrant further exploration.\u003c/p\u003e","manuscriptTitle":"Assessment of the elasticity of lipedematous tissue and the examination of the relationship between pain and fibrosis in lipedema","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-18 11:52:09","doi":"10.21203/rs.3.rs-7041394/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2025-11-07T22:23:06+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2025-10-22T16:13:37+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-10-02T11:58:09+00:00","index":2,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2025-09-02T15:19:11+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-08-15T08:33:10+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2025-08-10T18:04:02+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-07T12:01:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Journal of Obesity","date":"2025-07-04T18:48:32+00:00","index":"","fulltext":""},{"type":"checksFailed","content":"","date":"2025-07-04T10:55:39+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-03T21:16:49+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-obesity","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"ijo","sideBox":"Learn more about [International Journal of Obesity](http://www.nature.com/ijo/)","snPcode":"41366","submissionUrl":"https://mts-ijo.nature.com/cgi-bin/main.plex","title":"International Journal of Obesity","twitterHandle":"@intjobesity","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"6590838a-3b29-4cc1-9eb7-5fa6bf16d8ff","owner":[],"postedDate":"August 18th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":52932198,"name":"Health sciences/Medical research/Clinical trial design/Clinical trials"},{"id":52932199,"name":"Health sciences/Health care/Diagnosis"}],"tags":[],"updatedAt":"2026-03-15T07:06:49+00:00","versionOfRecord":{"articleIdentity":"rs-7041394","link":"https://doi.org/10.1038/s41366-026-02049-8","journal":{"identity":"international-journal-of-obesity","isVorOnly":false,"title":"International Journal of Obesity"},"publishedOn":"2026-03-14 04:00:00","publishedOnDateReadable":"March 14th, 2026"},"versionCreatedAt":"2025-08-18 11:52:09","video":"","vorDoi":"10.1038/s41366-026-02049-8","vorDoiUrl":"https://doi.org/10.1038/s41366-026-02049-8","workflowStages":[]},"version":"v1","identity":"rs-7041394","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7041394","identity":"rs-7041394","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}