World J Mens Health.  2024 Jan;42(1):157-167. 10.5534/wjmh.220241.

Extracorporeal Shockwave Therapy Alleviates Inflammatory Pain by Down-Regulating NLRP3 Inflammasome in Experimental Chronic Prostatitis and Chronic Pelvic Pain Syndrome

Affiliations
  • 1Department of Urology, College of Medicine, The Catholic University of Korea, Seoul, Korea
  • 2Catholic Integrative Medicine Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea
  • 3Department of Urology, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea
  • 4Department of Urology, Daegu Catholic University School of Medicine, Daegu, Korea
  • 5Department of Urology, University of California San Diego Medical Center, San Diego, CA, USA
  • 6Huons Meditech Co.,Ltd, Seongnam, Korea
  • 7Institute of Cannabis Research, Colorado State University-Pueblo, Pueblo, CO, USA
  • 8Green Medicine Co., Ltd, Busan, Korea
  • 9San Diego Veterans Affairs Health Care System, San Diego, CA, USA

Abstract

Purpose
To evaluate the anti-inflammatory and antioxidative effects of extracorporeal shockwave therapy (ESWT) on prostatitis and explore the mechanism of alleviating pain.
Materials and Methods
For in vitro testing, RWPE-1 cells were randomly divided into 5 groups: (1) RWPE-1 group (normal control), (2) LPS group (lipopolysaccharide inducing inflammation), (3) 0.1ESWT group (treated by 0.1 mJ/mm2 energy level), (4) 0.2ESWT group (treated by 0.2 mJ/mm2 energy level), and (5) 0.3ESWT group (treated by 0.3 mJ/mm2 energy level). After ESWT was administered, cells and supernatant were collected for ELISA and western blot. For in vivo testing, Sprague-Dawley male rats were randomly divided into 3 groups: (1) normal group, (2) prostatitis group, and (3) ESWT group (n=12 for each). Prostatitis was induced by 17 beta-estradiol and dihydrotestosterone (DHT) administration. Four weeks after ESWT, the pain index was assessed for all groups and prostate tissues were collected for immunohistochemistry, immunofluorescence, apoptosis analysis and, western blot.
Results
Our in vitro studies showed that the optimal energy flux density of ESWT was 0.2 mJ/mm2. In vivo, ESWT ameliorated discomfort in rats with prostatitis and inflammation symptoms were improved. Compared to normal rats, overexpressed NLRP3 inflammasomes triggered apoptosis in rats with prostatitis and this was improved by ESWT. TLR4-NFκB pathway was overactive after experimental prostatitis, compared to normal and ESWT groups, and prostatitis induced alterations in BAX/BAK pathway were inhibited by ESWT.
Conclusions
ESWT improved CP/CPPS by reducing NLRP3 inflammasome and ameliorated apoptosis via inhibiting BAX/BAK pathway in a rat model. TLR4 may play a key role in bonding NLRP3 inflammasome and BAX/BAK pathways. ESWT might be a promising approach for the treatment of CP/CPPS.

Keyword

Apoptosis; Extracorporeal shockwave therapy; Inflammasomes; Prostatitis
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