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ObjectivesLipedema is a chronic adipose tissue disorder characterized by disproportionate fat accumulation, lower extremity pain, functional impairment, and reduced quality of life. Although pain is a cardinal symptom, its underlying mechanisms remain incompletely understood. This study aimed to characterize sensitization-related pain phenotypes in women with lipedema by examining central sensitization (CS) and neuropathic -like pain features and their associations with lower extremity function, sleep quality, and health-related quality of life (HRQoL).MethodsIn this cross-sectional case-control study, 54 women with clinically diagnosed lipedema and 48 age-matched control participants were enrolled between March and October 2025. Pain phenotypes were assessed using the Central Sensitization Inventory (CSI) and Pain-DETECT questionnaire. Lower extremity function, sleep quality, and HRQoL were evaluated using Lower Extremity Functional Scale (LEFS), Jenkins Sleep Scale (JSS), and EuroQol-5D-3L (EQ-5D-3L), respectively.ResultsWomen with lipedema had significantly higher Pain-DETECT and CSI scores than controls, indicating greater neuropathic-like pain features and CS-related symptom burden (both p < .01). They also demonstrated poorer lower extremity function, greater sleep disturbance, and lower HRQoL. Pain-DETECT scores were positively correlated with CSI, anxiety, depression, and sleep disturbance scores. In multivariable analyses, LEFS independently predicted Pain-DETECT scores (B = -0.171, p = .015), whereas anxiety independently predicted CSI scores (B = 1.980, p = .002).ConclusionsWomen with lipedema exhibit prominent sensitization-related pain phenotypes associated with functional impairment, sleep disturbances, and reduced quality of life. Identification of these pain characteristics may improve clinical assessment, patient stratification, and multidisciplinary management of lower extremity symptoms in lipedema.