Application Of Low Intensity Extracorporeal Shock Wave In The Treatment Of Chronic Prostatitis/Chronic Pelvic Pain Syndrome

Objectives:Chronic prostatitis/chronic pelvic pain syndrome（CP/CPPS）is a common male urological disease characterized by chronic pelvic pain.Extracorporeal shock wave therapy（ESWT）has been used to treat patients with CP/CPPS,but the parameters used by ESWT are not uniformly determined.With the development of technology,low-intensity ESWT（Li-ESWT）is increasingly used in chronic inflammatory diseases.Herein,this study aims to assess the effects of ESWT with different energy flux densities on pelvic pain in CP/CPPS rats and to explore the mechanisms.Methods:The rat model of chronic prostatitis was established.A rat model of chronic prostatitis（CP）was induced by intraprostatic injection of 1%carrageenan.Li-ESWT with different energy flux densities（0.09 m J/mm~2,0.20 m J/mm~2,0.30 m J/mm~2,0.40m J/mm~2）was applied in the pelvic region of CP rats once a week for 4 weeks.Tactile allodynia test was performed using von Frey filaments to measure pelvic pain.After Li-ESWT,the prostate tissues were collected for HE and toluidine blue staining,immunohistochemistry,and ELISA analyses.Patients with prostatitis-like symptoms greater than or equal to three months were enrolled and received four sessions of Li-ESWT（once per week）.Each treatment session was conducted at a frequency of 3Hz with a preferred energy flow density（EFD）of 0.25 m J/mm~2ranging from0.20-0.30m J/mm~2.The scores of the National Institute of Health Chronic Prostatitis Symptoms Index（NIH-CPSI）,International Prostate Symptom Score（IPSS）,International Index of Erectile Function（IIEF-5）,and Visual Analogue Scale（VAS）were recorded to assess the remission of disease in the 0,1st,2nd,3rd,4th,5th,8th,and 16th weeks after Li-ESWT.A decrease of the NIH-CPSI score≥6 was regarded as the effectiveness standard of clinical treatment.All adverse reactions were strictly recorded during the period of treatment and follow-up.Results:In animal experiments,after 4 weeks of Li-ESWT,the prostate tissues of rats were stained with HE and toluidine blue.HE staining showed no obvious infiltration of inflammatory cells in the control group,but there were infiltration of lymphocytes and neutrophils in the prostate of CP model rats,and obvious hyperemia around glands,indicated that the prostatitis model was successfully established.However,inflammatory cell infiltration and hyperemia were reduced in the treatment groups with energy flow densities of 0.09 m J/mm~2,0.20 m J/mm~2,and 0.30 m J/mm~2,not of0.40m J/mm~2.Compared with other energy flow densities（0.09 m J/mm~2,0.30 m J/mm~2,0.40 m J/mm~2）,the effect of energy flow density at 0.20 m J/mm~2on pelvic pain and prostate injury was more obvious.We also found that the therapeutic effect may be related to the reduction of the total number of mast cells and degranulosa cells.In the chronic prostatitis/chronic pelvic pain syndrome clinical trial,we found that the NIH-CPSI pain score at baseline was 10.49±2.83 in 91 enrolled patients.Compared with baseline information prior to treatment,all valid questionnaire scores,except for erectile function IIEF-5,showed significant improvement at week 4（P<0.05）.In addition,NIH-CPSI and pain scores showed significant relief at week 1 of treatment initiation,while other measures（IIEF-5,VAS）showed late relief at week 2.The effective rates at the 1st,2nd,3rd,4th,5th,8th and 16th weeks were 28.57%,38.46%,47.25%,51.65%,57.30%,68.18%and 69.44%,respectively,showing a gradually increasing trend.There were no obvious adverse side effects during the whole treatment and follow-up.Conclusion:We found that Li-ESWT ameliorated pain symptoms in the pelvic region of carrageenan-induced CP model rats.When the frequency of 3 Hz,the number of pulses 500 times,once a week,and treatment for 4 weeks were used,0.20 m J/mm~2was the optimal EFD.Its therapeutic mechanism may be related to the reduction of the total number of mast cells and the number of degranulated cells.Similarly,the safety and efficacy of Li-ESWT in improving the symptoms of clinical CP/CPPS patients were also verified in the energy flux density range of 0.20-0.30 m J/mm~2.When the subjects can tolerate it,it is recommended to use 0.25 m J/mm~2as the preferred EFD scheme under the Li-ESWT scheme with a frequency of 3 Hz,a total of 2000 pulses,once a week,and treatment for 4 weeks.