ABSTRACT
PURPOSE: Urethral pain syndrome is a chronic condition characterized by disturbing feeling or server pain sensed at the urethra without specific treatment. This double-center, two-arm controlled trial aimed to explore the efficacy of electrical pudendal nerve stimulation (EPNS) versus intravesical instillation (II) of heparin and alkalinized lidocaine for urethral pain syndrome (UPS). METHODS: Eighty eligible patients took three sessions of EPNS, or 1 session of II per week, for 6 consecutive weeks. The primary end point was the change of pelvic pain and urgency/frequency symptom (PUF) score from baseline to week 6. Secondary outcome measures included changes of visual analogue scale (VAS) score and three sub-score extracted from PUF score. RESULTS: The enrolled participants were all included in the intention-to-treat analyses, and baseline characteristics between the two groups were well balanced. The post-treatment PUF score decreased by 10.0 (7.00, 16.50) in the EPNS group, and by 7.0 (3.00, 10.00) in the II group. At the closure of treatment, the medians of changes in symptom score, bother score, pain-related score and VAS score were 6.50 (4.25, 10.00), 4.00 (2.00, 6.00), 6.00 (5.00, 8.00),4.50 (2.25, 6.00), respectively, in the EPNS group, and 4.00 (2.00, 7.00), 3.00 (1.00, 3.00), 3.00 (2.00, 6.00), 2.00 (1.00, 4.00), respectively, in the II group. All the between-group differences were statistically significant. CONCLUSION: Compared with the II, the EPNS results in superior pain control and better relief of lower urinary tract symptoms, and deserves further attention. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03671993).
Subject(s)
Anesthetics, Local/therapeutic use , Chronic Pain/therapy , Electric Stimulation Therapy/methods , Fibrinolytic Agents/therapeutic use , Heparin/therapeutic use , Lidocaine/therapeutic use , Pelvic Pain/therapy , Pudendal Nerve , Urethral Diseases/therapy , Administration, Intravesical , Chronic Pain/physiopathology , Female , Humans , Intention to Treat Analysis , Lower Urinary Tract Symptoms/physiopathology , Lower Urinary Tract Symptoms/therapy , Male , Middle Aged , Pain Measurement , Pelvic Pain/physiopathology , Urethral Diseases/physiopathologyABSTRACT
BACKGROUND/AIMS: SU5416 is a potent inhibitor of receptor tyrosine kinases, including those of the vascular endothelial growth factor receptor, stem cell factor receptor, and platelet-derived growth factor receptor. Because of the overwhelming evidence favoring the role of aberrant hepatocyte growth factor (HGF)/Met signaling in the pathogenesis of various human cancers, various inhibitor strategies have been employed to therapeutically target this receptor. METHODS: Cell proliferation was determined by incorporation of [(3)H] thymidine. Invasiveness was assayed in Boyden Chambers with 8 microm Matrigel coated filters. Phosphorylation of ERK1/2, Akt by HGF stimulation was detected by Western blotting. RESULTS: We found that SU5416 inhibited motility scattering and the invasive activity of a hepatocellular carcinoma cell line HepG2 in vitro and growth in primary cultured hepatocytes induced by HGF. Consequently, tyrosine autophosphorylation of the c-met induced by HGF was inhibited in these cells by SU5416 in a dose-dependent manner. Furthermore, ERK1/2 and Akt phosphorylation, the signaling events down-stream of c-met activation were reduced. Moreover, SU5416 caused reversion in NIH3T3 fibroblasts transformed by the oncogenic form of the receptor, Tpr-Met. CONCLUSIONS: Inhibition of various solid tumors growth and metastasis by SU5416 may be partially attributed to blocking activation of the hepatocyte growth factor receptor.
