Jeon SH. et al., 2019: Extracorporeal shock wave therapy decreases COX-2 by inhibiting TLR4-NFκB pathway in a prostatitis rat model
Jeon SH, Zhu GQ, Kwon EB, Lee KW, Cho HJ, Ha US, Hong SH, Lee JY, Bae WJ, Kim SW.
Department of Urology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Catholic Integrative Medicine Research Institute, The Catholic University of Korea, Seoul, Republic of Korea.
BACKGROUND: This study aims to evaluate the effect of extracorporeal shock wave therapy (ESWT) on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and to explore the mechanism. METHODS: RWPE-2 cells were randomly divided into three groups: (a) RWPE-2 group (normal control), (b) LPS groups (lipopolysaccharide inducing inflammation) and (c) ESWT groups (LPS induced RWPE-2 treated by ESWT). After ESWT was administered, cells and supernatant were collected for enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. In vivo, Sprague-Dawley rats (n = 30) were randomly divided into three groups: (a) normal control group, (b) prostatitis groups, and (c) ESWT groups. Prostatitis rats were induced by 17 β-estradiol and dihydrotestosterone for 4 weeks. After ESWT, prostates of each group were collected for immunohistochemistry, Western blot analysis, and ELISA. RESULTS: ESWT improved prostatitis by attenuating inflammation (P < .01). ESWT downregulated the expression of cyclooxygenase 2 (COX-2) through inhibiting TLR4-NFκB pathway compared with the LPS group in vitro or prostatitis group in vivo (P < .05). TRAF2 mediates ERK1/2-COX2 pathway. ESWT promotes prostate tissue recovery by stimulating vascular endothelial growth factor expression (P < .01). ESWT could suppress apoptosis in the prostate. CONCLUSIONS: ESWT improved CP/CPPS and reduced inflammation by degrading COX-2 in microenvironment through TLR4-NFκB-inhibiting pathway. TRAF2 regulator in ERK1/2-COX-2 inhibition significantly reduced inflammation, thus suggesting ESWT may be a potential and promising treatment for CP/CPPS.
Prostate. 2019 Sep;79(13):1498-1504. doi: 10.1002/pros.23880. Epub 2019 Aug 2.
Shock waves exhibit a surprising variety of positive effects in different situations like e.g. in the treatment of the chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS).
A recent review and metaanalysis (1) revealed that since the first clinical study on ESWT for CP/CPPS by Zimmerman et al. (2) in 2009 5 additional randomized controlled trials assessing the effects of Li‐ESWT compared to sham group have been published. The common nominator of these clinical studies showing positive short term effects and research papers on this subject is that etiology of CP/CPPS is unknown. The present study uses a rat model with induction of prostatitis by 17 β‐estradiol and dihydrotestosterone for 4 weeks. In a completely different rat model inducing prostatitis by Capsaicin injection ESWT reduced pain reaction and inflammatory tissue reactions (3). This seems to suggest that the results seen are not so much based on the pathology but on the ESWT effect on the prostate. It may be worth to study the ESWT effects on normal prostate to understand its action on diseased tissue.
1 Yuan P et al. Efficacy of low-intensity extracorporeal shock wave therapy for the treatment of chronic prostatitis/chronic pelvic pain syndrome: A systematic review and meta-analysis. Neurourol Urodyn. 2019 Aug;38(6):1457-1466. doi: 10.1002/nau.24017. Epub 2019 Apr 29.
2 Zimmermann R et al. Extracorporeal shock wave therapy for the treatment of chronic pelvic pain syndrome in males: a randomised, double-blind, placebo-controlled study.
Eur Urol. 2009 Sep;56(3):418-24. doi: 10.1016/j.eururo.2009.03.043.
3 Wang H-J. et al. Low Energy Shock Wave Therapy Inhibits Inflammatory Molecules and Suppresses Prostatic Pain and Hypersensitivity in a Capsaicin Induced Prostatitis Model in Rats. Int. J. Mol. Sci. 2019, 20, 4777; doi:10.3390/ijms20194777 Free PMC Article