Divergent Roles of VEGF and TNF-α in Functional Impairment Among Patients with Carpal Tunnel Syndrome

Upper limb disorders, including carpal tunnel syndrome (CTS), are a common cause of pain, functional limitations, and reduced quality of life. Increasing attention has been directed toward the role of inflammatory and angiogenic mediators in the pathophysiology of CTS and their potential relationship with patient-reported functional outcomes. The aim of this study was to evaluate selected cytokines as potential markers of upper limb disability assessed using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire. This cross-sectional study included 55 patients with idiopathic CTS referred for surgical treatment. Functional impairment was assessed using the DASH questionnaire, and concentrations of selected inflammatory and angiogenic mediators-IL-4, IL-6, MCP-1, TNF-α, VEGF, and fraktalkine-were measured in synovial tissue samples; these markers were selected based on their established roles in inflammation, angiogenesis, and nociceptive modulation relevant to CTS pathophysiology. VEGF was identified as a significant predictor of DASH category (p = 0.032), with higher concentrations associated with a lower likelihood of severe upper limb dysfunction. In contrast, higher TNF-α levels were associated with an increased risk of severe disability (p = 0.031). Other cytokines did not demonstrate significant associations with functional impairment. These findings suggest that selected inflammatory and angiogenic mediators were associated with the severity of functional disability in CTS and warrant investigation in prospective longitudinal studies to clarify their potential role alongside patient-reported outcome measures.