Short-term effects of lumbar sympathetic ganglion block on swelling and fibrosis-related changes in a rat model of chronic secondary hind-limb lymphedema

This study aimed to evaluate the therapeutic efficacy and potential mechanisms of lumbar sympathetic ganglion block (LSGB) in a rat model of chronic secondary hind-limb lymphedema. A chronic unilateral hind-limb lymphedema model was established by popliteal lymph node dissection, excision of collecting lymphatic vessels, and two sessions of localized irradiation. After 24 weeks, 18 rats with persistent chronic lymphedema were randomly assigned to the LSGB, sham injection, or untreated control groups (n = 6 per group). LSGB was performed under ultrasound guidance using 0.2% ropivacaine. Successful sympathetic blockade was confirmed by infrared thermography. Hind-limb volume was assessed using the water-displacement method. Indocyanine green near-infrared fluorescence lymphography was used to confirm impaired lymphatic drainage in the model. Epidermal and dermal thicknesses and collagen deposition were evaluated histologically. Transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor receptor-3 (VEGFR-3), and lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) were assessed using immunofluorescence staining, and TGF-β1 protein expression was further examined by Western blotting. LSGB increased the skin temperature of the affected hind limb, confirming effective sympathetic blockade. One day after completion of the LSGB protocol, affected hind-limb volume was reduced relative to the pretreatment value, whereas no significant change was observed in the sham injection or untreated control groups. LSGB was also associated with reduced epidermal and dermal thicknesses and decreased collagen deposition. Immunofluorescence staining demonstrated lower TGF-β1 expression and increased VEGFR-3 and LYVE-1 expression after LSGB. Western blotting further confirmed reduced TGF-β1 protein expression in the LSGB group. LSGB reduced hind-limb swelling and tissue fibrosis in rats with chronic secondary lymphedema. These changes were associated with lower TGF-β1 expression and increased expression of the lymphatic-related markers VEGFR-3 and LYVE-1. The findings provide preclinical support for further investigation of LSGB as a minimally invasive adjunctive treatment for refractory lower-limb lymphedema.