Low-Intensity Pulsed Ultrasound Regulates Th17/Treg Balance With Potential Association With the IL-1β/IL1R1/MyD88 Signaling Pathway to Alleviate Pelvic Pain in a Rat Prostatitis Model.

Abstract

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common urinary tract disorder in males. Low-intensity pulsed ultrasound (LIPUS), a non-invasive therapeutic modality, has shown potential in alleviating inflammation associated with this condition. However, the underlying mechanisms through which LIPUS exerts its effects on CP/CPPS remain largely unknown. This study aimed to investigate the impact of LIPUS at varying intensities and durations on pain relief in a rat model of CP/CPPS. METHODS: A CP/CPPS model was established by injecting 1% carrageenan into the prostate of rats. LIPUS at three different energy intensities (T1, T2 and T3: 0.5, 1.0 and 1.5 W/cm², respectively) was applied to the pelvic region for 10 min daily over a period of 2 or 4 weeks. Pain relief and prostate injury were evaluated to assess the therapeutic efficacy of LIPUS. The mechanism study focuses on the role of LIPUS in regulating the Th17/Treg balance (by detecting CD4+ T cells in the prostate through flow cytometry and the expression of Foxp3/interleukin-17A (IL-17A) in prostate tissue through immunohistochemistry) as well as its effects on the IL-1β/IL1R1/MyD88 signaling pathway in prostate tissue (by detecting pathway protein expression through Western blot and measuring inflammatory factor concentration using enzyme-linked immunosorbent assay). RESULTS: To identify the optimal parameter of LIPUS for CP/CPPS, we treated model rats with LIPUS at intensities of 0.5, 1.0 or 1.5 W/cm² for 2 or 4 weeks, and evaluated the therapeutic effects using multiple endpoints. Among these intensities, LIPUS at 1.0 W/cmenergy/4 weeks exhibited the most prominent efficacy: compared with the model group, it significantly alleviated pelvic pain and reduced prostate inflammation scores. Further mechanistic studies demonstrated that, relative to the model group, LIPUS at 1.0 W/cmenergy/4 weeks could regulate Th17/Treg balance and downregulate the expression of related proteins, including IL-1β, IL1R1 and MyD88. CONCLUSION: LIPUS, when administered at 1.0 W/cm² for 4 weeks, showed superior efficacy in reducing pain in CP/CPPS rats. These findings suggest that LIPUS may offer a promising therapeutic approach for CP/CPPS and provide insights into its underlying mechanism of action.