Central Sensitization, Pain, and Psychosocial Factors in Individuals with Lipedema: A Cross-Sectional Study

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Abstract
To compare central sensitization (CS), pressure pain threshold (PPT), and psychosocial factors between women with lipedema and healthy controls and to identify variables associated with CS in lipedema. In this cross-sectional study, 30 women with clinically diagnosed lipedema and 30 age-matched healthy controls were assessed.CS was measured with the Central Sensitization Inventory (CSI), and PPT was recorded bilaterally at the deltoid, lateral thigh, and medial knee using an algometer, pain-related cognitions with the Pain Catastrophizing Scale (PCS), and mood with the Hospital Anxiety and Depression Scale (HADS). Compared with controls, the lipedema group had lower PPTs at all sites (all p ≤ 0.001) and higher CSI scores (p ≤ 0.001). CS prevalence (CSI ≥ 40) was 70.0% in lipedema versus 23.3% in controls (p≤ 0.001). HADS-Depression (p = 0.001), HADS-Anxiety (p = 0.017), and PCS helplessness, magnification, rumination, and total scores (all p ≤ 0.006) were higher in lipedema. In the total sample, CSI correlated negatively with all PPT values (all p ≤ 0.003) and positively with HADS-Depression/Anxiety and PCS scores (all p < 0.001). In multivariable analysis among patients with lipedema, higher CSI was associated with greater BMI (β = 1.117, p=0.018), hypertension (β = 15.918, p = 0.009), diabetes mellitus (β = 16.663, p = 0.002), higher VAS pain (β = 0.368, p = 0.002), lower right medial knee PPT (β = - 3.891, p = 0.011), and higher HADS-Depression (β = 1.307, p = 0.038). Lipedema is associated with lower pain thresholds and higher CS, alongside greater depressive and anxiety symptoms and pain catastrophizing. CS in lipedema appears linked to pain intensity, depressive symptoms, and cardiometabolic comorbidities. These findings suggest that management should complement peripheral approaches with strategies targeting central pain mechanisms and psychosocial factors. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

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