Effect of acupuncture on quality of life in patients with chronic prostatitis/chronic pelvic pain syndrome: a randomized controlled trial. / é’ˆåˆºæ²»ç–—å¯¹æ ¢æ€§å‰åˆ—è ºç‚Ž/æ ¢æ€§ç›†è ”ç–¼ç—›ç»¼åˆå¾æ‚£è€ ç”Ÿæ´»è´¨é‡çš„å½±å“ï¼šéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To observe the effect and safety of acupuncture on quality of life, pain, and prostate symptoms in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: Seventy patients with CP/CPPS were randomly divided into an acupuncture group (35 cases, 1 case was eliminated) and a sham acupuncture group (35 cases, 3 cases dropped out). The patients in the acupuncture group were treated with routine acupuncture at bilateral Zhongliao (BL 33), Huiyang (BL 35), Shenshu (BL 23) and Sanyinjiao (SP 6), while the patients in the sham acupuncture group were treated with shallow needling at non-meridian and non-acupoint points beside bilateral Zhongliao (BL 33), Huiyang (BL 35), Shenshu (BL 23) and Sanyinjiao (SP 6),without manipulation to induce arrival of qi (deqi). Both groups retained the needles for 30 min, with one session every other day, three times a week, for a total of 8 weeks (24 sessions). Before and after treatment, and at the follow-up of 24 weeks after treatment completion, the scores of MOS 36-item short-form health survey (SF-36, including 8 dimensions of physical function [PF], role physical function [RP], bodily pain [BP], general health status [GH], vitality [VT], social function [SF], role emotional [RE], and mental health [MH], which can be summarized as physical component summary [PCS] and mental component summary [MCS]), pelvic pain visual analogue scale (VAS), National Institutes of Health chronic prostatitis symptom index (NIH-CPSI), and international prostate symptom score (IPSS) were evaluated, and safety of both groups was assessed. RESULTS: After treatment and at the follow-up, the scores of each dimension and PCS, MCS scores of SF-36 in the acupuncture group were higher than those before treatment (P<0.05, P<0.01); compared before treatment, the RP, BP, and SF scores and PCS score in the sham acupuncture group were increased after treatment (P<0.05, P<0.01). After treatment, the acupuncture group had higher scores in RP, BP, GH, MH and PCS, MCS than those in the sham acupuncture group (P<0.05, P<0.01); at the follow-up, except for PF and RE dimensions, the scores in each dimension and PCS, MCS scores in the acupuncture group were higher than those in the sham acupuncture group (P<0.05, P<0.01). After treatment and at the follow-up, pelvic pain VAS, NIH-CPSI, IPSS scores in the acupuncture group were lower than those before treatment (P<0.01); in the sham acupuncture group, pelvic pain VAS, NIH-CPSI scores were lower after treatment, and NIH-CPSI score at the follow-up was lower compared with those before treatment (P<0.01). After treatment and at the follow-up, pelvic pain VAS, NIH-CPSI, IPSS scores in the acupuncture group were lower than those in the sham acupuncture group (P<0.01, P<0.05). No significant adverse reactions were observed in both groups, and the incidence rates of adverse reactions had no significant difference (P>0.05). CONCLUSIONS: Acupuncture could effectively improve the quality of life, reduce pain levels, alleviate prostate symptoms, and shows favorable long-term efficacy in patients with CP/CPPS.

Sodium butyrate alleviates experimental autoimmune prostatitis by inhibiting oxidative stress and NLRP3 inflammasome activation via the Nrf2/HO-1 pathway.

BACKGROUND: Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) leads to severe discomfort in males and loss of sperm quality. Current therapeutic options have failed to achieve satisfactory results. Sodium butyrate (NaB) plays a beneficial role in reducing inflammation, increasing antioxidant capacities, and improving organ dysfunction; additionally NaB has good safety prospects and great potential for clinical application. The purpose of the current research was to study the effect of NaB on CP/CPPS and the underlying mechanisms using a mouse model of experimental autoimmune prostatitis (EAP) mice. METHODS: The EAP mouse model was successfully established by subcutaneously injecting a mixture of prostate antigen and complete Freund's adjuvant. Then, EAP mice received daily intraperitoneal injections of NaB (100, 200, or 400 mg/kg/day) for 16 days, from Days 26 to 42. We then explored anti-inflammatory potential mechanisms of NaB by studying the effects of Nrf2 inhibitor ML385 and HO-1 inhibitor zinc protoporphyrin on prostate inflammation and pelvic pain using this model. On Day 42, hematoxylin-eosin staining and dihydroethidium staining were used to evaluate the histological changes and oxidative stress levels of prostate tissues. Chronic pelvic pain was assessed by applying Von Frey filaments to the lower abdomen. The levels of inflammation-related cytokines, such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor were detected by enzyme-linked immunosorbent assay. The regulation of Nrf2/HO-1 signaling pathway and the expression of NLRP3 inflammasome-related protein in EAP mice were detected by western blot analysis assay. RESULTS: Compared with the EAP group, chronic pain development, histological manifestations, and cytokine levels showed that NaB reduced the severity of EAP. NaB treatment could inhibit NLRP3 inflammasome activation. Mechanism studies showed that NaB intervention could alleviate oxidative stress in EAP mice through Nrf2/HO-1 signal pathway. Nrf2/HO-1 pathway inhibitors can inhibit NaB -mediated oxidative stress. The inhibitory effect of NaB on the activation of NLRP3 inflammasome and anti-inflammatory effect can also be blocked by Nrf2/HO-1 pathway. CONCLUSIONS: NaB treatment can alleviates prostatic inflammation and pelvic pain associated with EAP by inhibiting oxidative stress and NLRP3 inflammasome activation via the Nrf2/HO-1 pathway. NaB has the potential as an effective agent in the treatment of EAP.

4-Octyl itaconate alleviates experimental autoimmune prostatitis by inhibiting the NLRP3 inflammasome-induced pyroptosis through activating Nrf2/HO-1 pathway.

BACKGROUND: Chronic prostatitis demonstrates a prevalence rate of nearly 5%-10% among young and middle-aged individuals, significantly affecting their daily lives. Researchers have obtained significant outcomes investigating the anti-inflammatory properties of itaconic acid (IA) and its derivative, 4-Octyl itaconate (4-OI), against diverse chronic inflammatory disorders, such as osteoarthritis and airway inflammation. Nevertheless, whether IA can also exert anti-inflammatory effects in chronic prostatitis requires extensive research and validation. METHODS: Human prostate tissues obtained through transurethral prostate resection (TURP) from individuals were divided into three groups based on different levels of inflammation using hematoxylin and eosin staining (H&E). Subsequently, immunohistochemistry (IHC) was employed to detect the expression of immune-responsive gene 1 (IRG-1) in these different groups. The animal experiment of this study induced experimental autoimmune prostatitis (EAP) in nonobese diabetic mice through intradermal prostate antigen injection and complete Freund's adjuvant. Then, the experimental group received intraperitoneal injections of different doses of 4-OI, while the control group received injections of saline. Western blot (WB), H&E staining, and TUNEL staining helped analyze the prostate tissues, while enzyme-linked immunosorbent assay (ELISA) helped evaluate serum inflammatory factors. Reactive oxygen species, superoxide dismutase (SOD), and malondialdehyde (MDA) were assessed for oxidative stress across experimental groups. RESULTS: IHC analysis of human prostate tissue depicts that IRG-1 expression enhances as prostate inflammation worsens, highlighting the critical role of IA in human prostatitis. The application of 4-OI increased Nrf2/HO-1 expression while inhibited NLRP3 expression following the WB results, and its application resulted in a decrease in cell pyroptosis in prostate tissue, demonstrated by the results of TUNEL staining. Administering a Nrf2 inhibitor ML385 1 h before intraperitoneal injection of 50 mg/kg 4-OI reversed the previous conclusion, further confirming the above conclusion from another perspective. Meanwhile, the ELISA results of serum inflammatory factors (IL-1ß, IL-6, and TNF-α), as well as the measurements of oxidative stress markers MDA and SOD, further confirmed the specific anti-inflammatory effects of 4-OI in EAP. CONCLUSIONS: The present study indicates that 4-OI can alleviates EAP by inhibiting the NLRP3 inflammasome-induced pyroptosis through activating Nrf2/HO-1 pathway, which may facilitate a novel approach toward prostatitis treatment.

Astaxanthin alleviates chronic prostatitis/chronic pelvic pain syndrome by increasing colonization of Akkermansia muciniphila in the intestine.

BACKGROUND: Astaxanthin (AST) is a natural compound with anti-inflammatory/immunomodulatory properties that has been found to have probiotic properties. However, the role and mechanism of AST in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are still not fully understood. PURPOSE: The aim of this study was to evaluate the effect of AST on CP/CPPS and elucidate the mediating role of the gut microbiota. MATERIALS AND METHODS: An experimental autoimmune prostatitis (EAP) mouse model was utilized to test the potential role of AST on CP/CPPS. Antibiotic cocktail (ABX) treatment and fecal microbiota transplantation (FMT) were used to elucidate the gut microbiota-mediated effects on AST. In addition, 16S rRNA gene sequencing and qRT-PCR analyses were used to analyze changes in the gut microbiota of EAP mice and CP/CPPS patients. Finally, the mechanism by which AST exerts a protective effect on CP/CPPS was explored by untargeted metabolomics and gut barrier function assays. RESULTS: Oral administration of AST reduced prostate inflammation scores, alleviated tactile sensitization of the pelvic region in EAP mice, reduced CD4+ T cell and CD68+ macrophage infiltration in the prostatic interstitium, and inhibited the up-regulation of systemic and localized pain/pro-inflammatory mediators in the prostate. After ABX, the protective effect of AST against CP/CPPS was attenuated, whereas colonization with fecal bacteria from AST-treated EAP mice alleviated CP/CPPS. 16S rRNA gene sequencing and qRT-PCR analyses showed that Akkermansia muciniphila in the feces of EAP mice and CP/CPPS patients showed a trend toward a decrease, which was associated with poor progression of CP/CPPS. In contrast, oral administration of AST increased the relative abundance of A. muciniphila, and oral supplementation with A. muciniphila also alleviated inflammation and pain in EAP mice. Finally, we demonstrated that both AST and A. muciniphila interventions increased serum levels of SCFAs acetate, up-regulated expression of colonic tight junction markers, and decreased serum lipopolysaccharide levels in EAP mice. CONCLUSION: Our results showed that AST improved CP/CPPS by up-regulating A. muciniphila, which provides new potentially effective strategies and ideas for CP/CPPS management.

Research Trends of Acupuncture Therapy on Chronic Pelvic Pain Syndrome from 2000 to 2022: A Bibliometric Analysis.

Background: Acupuncture is considered an important means of analgesic, which has been widely used in chronic pelvic pain syndrome (CPPS) management and treatment in recent years, published a large number of related documents. However, the relevant literature in this field has not been summarized and quantitatively analyzed. Therefore, this study aims to analyze the hotspots and predicting future research trends of acupuncture on pelvic pain syndrome. Methods: Search for the relevant publications of the web of science database from 2000 to 2022 about the treatment of acupuncture on chronic pelvic pain syndrome. The Citespace software and VosViewer software are used to analyze the visualization of the countries, institutions, authors, keywords and references and references in the literature. Results: A total of 173 publications were included. The annual number of essays gradually showed an overall growth trend over time. Medicine magazine is the most published journal in this field. J UROLOGY and Acupunct Med are the most cited journals and the most influential magazines; The most active and influential country is China, and the most produced institutions are Beijing University of Chinese Medicine; The most produced authors are Liu Zhishun. The most cited and most influential authors are Nickel JC and Armour M; keywords and cited reference analysis show that the quality of life, mechanism research, alternative medicine and electro-acupuncture will be the scientific hotspot of acupuncture treatment for chronic pelvic pain syndrome. Conclusion: This study shows that acupuncture on CPPS is increasingly valued and recognized. The future research hotspots will focus on the effects and mechanisms. In the future, more high-quality animal basic research will be required to explore the exact mechanism of acupuncture on CPPS. In addition, different parameters of acupuncture such as electric-acupuncture, stimulating frequency, duration and strength are also the focus of future research. More clinical trials are required to verify its safety and effectiveness.

Comparing the effectiveness of extracorporeal shockwave therapy and myofascial release therapy in chronic pelvic pain syndrome: study protocol for a randomized controlled trial.

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome is a highly prevalent syndrome. Previous studies showed that extracorporeal shockwave therapy and myofascial release therapy could improve the quality of life in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Theoretically, combined therapy with extracorporeal shockwave therapy and myofascial release therapy will likely have significant advantages in treating CP/CPPS. We, therefore, present a protocol for conducting a well-designed randomized controlled trial to compare the efficacy and safety of each therapy. METHODS: The proposed study will be a three-group randomized control trial (RCT) design that includes 150 participants from Zhongda Hospital Affiliated to Southeast University, with equal allocation of participants to the three intervention groups. The study duration will be 8 weeks, which includes a 4-week treatment period and a 4-week follow-up period. The primary outcome will be the changes in surface electromyography (sEMG) assessment and National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI). The secondary outcomes will include the changes in three-dimensional quantification, shear wave elastography (SWE), and sympathetic skin response (SSR) testing. Assessments will be conducted before the intervention (T0), before the 5th intervention (T1), immediately after the 8th intervention (T2), and the 4th week after the end of the 8th intervention (T3). DISCUSSION: This trial will compare the differences in efficacy between single extracorporeal shockwave therapy, single myofascial release therapy, and combined therapy to select the most appropriate treatment option for patients with CP/CPPS. The possible pathogenesis of CP/CPPS would also be analyzed by comparing the intercorrelation between each objective and subjective measurement (NIH-CPSI score, sEMG, SWE, SSR). TRIAL REGISTRATION: The name of the registry: Extracorporeal Shockwave and Myofascial Release Therapy in Chronic Pelvic Pain Syndrome. REGISTRATION NUMBER: NCT05659199. Date of registration: December 2022.

The Role of Acupuncture and Its Related Mechanism in Treating Chronic Prostatitis/Chronic Pelvic Pain Syndrome.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is one of the most common diseases in urology, and its prevalence has been increasing, causing serious urogenital problems in men. Several targeted oral drug therapies exist to treat the pelvic pain experienced in this disease. However, these therapies may have potential adverse effects, and due to the unique location of the prostate, delivery of medications to the target lesion is difficult. Consequently, many patients seek alternative therapies. Acupuncture is a well-established treatment method in traditional Chinese medicine that can improve CP/CPPS symptoms and reduce pain. However, previous systematic reviews overlooked the significance of the characteristics and mechanisms of acupuncture therapy. This study aimed to summarize the characteristics and benefits of acupuncture therapy for CP/CPPS based on relevant literature and predict and analyze its related mechanisms.

[Acupuncture for chronic prostatitis/chronic pelvic pain syndrome: a randomized controlled trial].

OBJECTIVE: To observe the short-term efficacy, long-term efficacy and safety of acupuncture for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: Forty-two patients with CP/CPPS were randomly divided into an acupuncture group (21 cases, 1 case dropped off) and a sham acupuncture group (21 cases). The patients in the acupuncture group were treated with acupuncture at bilateral Zhongliao (BL 33), Huiyang (BL 35), Shenshu (BL 23) and Sanyinjiao (SP 6); the needling depth of Zhongliao (BL 33) and Huiyang (BL 35) was 60 to 80 mm, while Shenshu (BL 23) and Sanyinjiao (SP 6) was directly punctured of 30 mm. The patients in the sham acupuncture group were treated with acupuncture at non-acupoints, including points 2 cm next to Shenshu (BL 23), Zhongliao (BL 33) and Huiyang (BL 35), and the midpoint of the connecting line between the spleen meridian and the kidney meridian. All the non-acupoints were treated with directly puncture of 2 to 3 mm. The needles were left for 30 min in both groups, once every other day in the first four weeks, three times a week, and twice a week in the next four weeks, totally 20 treatments. Before treatment, after treatment and in follow-up of 24 weeks after treatment completion, the National Institutes of Health-chronic prostatitis symptom index (NIH-CPSI) score and urinary flow rate were observed in both groups; the clinical efficacy and safety were evaluated. RESULTS: Compared with those before treatment, the pain and discomfort scores, urination symptoms scores, quality of life scores and total scores of NIH-CPSI in both groups were reduced after treatment in the two groups (P<0.01), while each item score and total score of NIH-CPSI in the acupuncture group were reduced in follow-up (P<0.01, P<0.05). After treatment and in follow-up, each item score and total score of NIH-CPSI in the acupuncture group were lower than those in the sham acupuncture group (P<0.05, P<0.01). After treatment, the maximum and average urinary flow rates in the acupuncture group were higher than those before treatment (P<0.05), and the average urinary flow rate in the acupuncture group was higher than that in the sham acupuncture group (P<0.05). The total effective rate was 75.0% (15/20) in the acupuncture group, which was higher than 42.9% (9/21) in the sham acupuncture group (P<0.05). No significant adverse reactions were observed in the two groups, and there was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). CONCLUSION: Acupuncture could effectively alleviate the clinical symptoms, improve quality of life, and has a sustained, safe and reliable therapeutic effect in patients with CP/CPPS.

Impact of ejaculation upon effect of acupuncture on chronic prostatitis/chronic pelvic pain syndrome: Secondary analysis of a randomized controlled trial.

Background: Acupuncture can improve chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Ejaculation frequencies might impact the conditions of CP/CPPS. The present study aimed to explore the impact of different ejaculation frequencies on the effect of acupuncture among men with CP/CPPS. Methods: This was a secondary analysis of the data from a multicenter, randomized, clinical trial. Eligible participants were patients with moderate to severe CP/CPPS, who had taken 8-week acupuncture treatment, and followed until week 32. Participants fell into the category of 0-3, 4-7, or at least 8 according to their monthly ejaculation frequencies reported at baseline. The primary outcome was the proportion of responders, defined as men who reported at least 6 points reduction from baseline in the National Institute of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) total score at weeks 8 and 32. Results: 214 participants were included in this secondary analysis, of whom 42 reported a monthly ejaculation frequency of 0-3, 89 reported a frequency of 4-7, and 83 reported a frequency of at least 8. At week 8, 52.20% participants with an ejaculation frequency of 0-3 responded to the acupuncture treatment, 65.38% participants with a frequency of 4-7 responded, and 63.09% participants with a frequency of at least 8 responded. At week 32, 56.14%, 59.57%, and 68.36% participants responded in the three groups, respectively. No significant differences were observed between three groups (all P>0.05). Conclusion: Acupuncture can improve symptoms of CP/CPPS, regardless of ejaculation frequencies. Ejaculation frequencies may not affect the efficacy of acupuncture on CP/CPPS among Chinese men. Trial registration: ClinicalTrials.gov, NCT03213938.

Extracorporeal shock wave therapy in association with bromelain and escin for the management of patients affected by chronic prostatitis/chronic pelvic pain syndrome.

Extracorporeal shock wave therapy (ESWT) has been purposed for the management of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) with encouraging results. Phytotherapeutic compounds have been used in everyday clinical practice for patients with CP/CPSS due to their anti-inflammatory properties. The present study aimed to investigate the effects of ESWT in association with the use of bromelain and escin extracts in patients with CP/CPSS. For this purpose, 95 patients with a clinical diagnosis of CP/CPSS were enrolled in the study. The patients were randomly allocated to either the ESWT plus bromelain and escin group (group A; n=48) or the ESWT only group (group B; n=47). A total of five weekly ESWT treatment sessions were administered alone or in combination with bromelain and escin. Each session consisted of 3,000 focused shock waves. Doses of 160 and 500 mg/day bromelain and escin were administered respectively for 5 weeks. The changes in urinary symptoms, pain and quality of life were considered the main outcome measures and were assessed at baseline, and at 4, 12 and 24 weeks of follow-up. Urinary symptoms, pain and quality of life were evaluated using the international prostatic symptoms score (IPSS), visual analog scale (VAS) and the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI). After 4 weeks, the mean VAS score, mean IPSS and mean satisfaction rate score had significantly improved in patients receiving ESWT plus bromelain and escin. After 12 weeks, the mean IPSS and mean satisfaction rate score were stable in the ESWT plus bromelain and escin group, while the mean VAS score was significantly lower when compared with the baseline values in both groups. On the whole, the present study demonstrates that in patients affected by CP/CPPS, treatment with ESWT plus bromelain and escin leads to pain resolution, and both treatments improve the IPSS, VAS and NIH-CPSI results.

Acupuncture for chronic prostatitis/chronic pelvic pain syndrome: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the short-term efficacy, long-term efficacy and safety of acupuncture for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).@*METHODS@#Forty-two patients with CP/CPPS were randomly divided into an acupuncture group (21 cases, 1 case dropped off) and a sham acupuncture group (21 cases). The patients in the acupuncture group were treated with acupuncture at bilateral Zhongliao (BL 33), Huiyang (BL 35), Shenshu (BL 23) and Sanyinjiao (SP 6); the needling depth of Zhongliao (BL 33) and Huiyang (BL 35) was 60 to 80 mm, while Shenshu (BL 23) and Sanyinjiao (SP 6) was directly punctured of 30 mm. The patients in the sham acupuncture group were treated with acupuncture at non-acupoints, including points 2 cm next to Shenshu (BL 23), Zhongliao (BL 33) and Huiyang (BL 35), and the midpoint of the connecting line between the spleen meridian and the kidney meridian. All the non-acupoints were treated with directly puncture of 2 to 3 mm. The needles were left for 30 min in both groups, once every other day in the first four weeks, three times a week, and twice a week in the next four weeks, totally 20 treatments. Before treatment, after treatment and in follow-up of 24 weeks after treatment completion, the National Institutes of Health-chronic prostatitis symptom index (NIH-CPSI) score and urinary flow rate were observed in both groups; the clinical efficacy and safety were evaluated.@*RESULTS@#Compared with those before treatment, the pain and discomfort scores, urination symptoms scores, quality of life scores and total scores of NIH-CPSI in both groups were reduced after treatment in the two groups (P<0.01), while each item score and total score of NIH-CPSI in the acupuncture group were reduced in follow-up (P<0.01, P<0.05). After treatment and in follow-up, each item score and total score of NIH-CPSI in the acupuncture group were lower than those in the sham acupuncture group (P<0.05, P<0.01). After treatment, the maximum and average urinary flow rates in the acupuncture group were higher than those before treatment (P<0.05), and the average urinary flow rate in the acupuncture group was higher than that in the sham acupuncture group (P<0.05). The total effective rate was 75.0% (15/20) in the acupuncture group, which was higher than 42.9% (9/21) in the sham acupuncture group (P<0.05). No significant adverse reactions were observed in the two groups, and there was no significant difference in the incidence of adverse reactions between the two groups (P>0.05).@*CONCLUSION@#Acupuncture could effectively alleviate the clinical symptoms, improve quality of life, and has a sustained, safe and reliable therapeutic effect in patients with CP/CPPS.

Acupuncture for Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A GRADE-assessed Systematic Review and Meta-analysis.

Context: Acupuncture is a promising therapy for relieving symptoms in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), which affects 9-16% of adult men worldwide. Objective: This study aims to explore the efficacy and safety of acupuncture for CP/CPPS. Evidence acquisition: Nine electronic databases were searched. Only randomized controlled trials were included. Two reviewers extracted data and assessed the risk of bias of trials using the revised Cochrane risk-of-bias (RoB 2.0) tool. Stata 17.0 was used to analyze the data. Evidence synthesis: Twelve trials were included. The results of a meta-analysis showed that acupuncture had larger effect sizes (standardized mean difference [SMD] = -1.20, confidence interval or CI [-1.69, -0.71], acupuncture compared with sham acupuncture; SMD = -1.01, CI [-1.63, -0.38], acupuncture compared with medication; SMD = -0.91, CI [-1.29, -0.54], acupuncture plus medication compared with medication) in reducing the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) total score. In decreasing NIH-CPSI pain domain score, acupuncture also led to larger effect sizes (SMD = -0.94, CI [-1.18, -0.70], acupuncture compared with sham acupuncture; SMD = -1.04, CI [-1.29, -0.79], acupuncture compared with medication; SMD = -0.85, CI [-1.23, -0.48], acupuncture plus medication compared with medication), whereas the effect sizes in the reduction of NIH-CPSI urinary domain and quality of life domain scores were medium. Compared with sham acupuncture and medication, acupuncture appears to be more effective in improving the global response rate. Results from four trials indicated that acupuncture was better than sham acupuncture in decreasing the International Prostate Symptom Score. No serious adverse effects were found in the acupuncture treatment. Conclusions: Current evidence supports acupuncture as an effective treatment for CP/CPPS-induced symptoms, particularly in relieving pain. Comprehensive acupuncture treatment according to individual symptoms should be considered in future clinical practice and trials for CP/CPPS. Patient summary: In this study, we further verified the efficacy of acupuncture in patients with chronic prostatitis/chronic pelvic pain syndrome, especially in reducing pain.

Effect of electroacupuncture on inflammatory signal expression in local tissues of rats with chronic pelvic pain syndrome based on purinergic 2X7 receptor/NOD-like receptor pyrin domain-containing 3 signal pathway.

OBJECTIVES: To study the expression of inflammatory signal in local prostate tissue of chronic pelvic pain syndrome (CPPS) rats by electroacupuncture (EA) of Guanyuan (CV4), Zhongji (CV3), Huiyang (BL35) and Sanyinjiao (SP6), and to explore the possible mechanism of anti-inflammatory and analgesic effects of EA. METHODS：A total of 36 Sprague-Dawley male rats were randomly divided into three groups: control, model and EA (n=12 rats/group). The CPPS model was made by injection of CFA into ventral lobes of the prostate (0.1 mL). Electric acupuncture apparatus was applied to stimulate Guanyuan (CV4), Zhongji (CV3), bilateral Huiyang (BL35) and Sanyinjiao (SP6) acupoints in EA group. The general condition of rats was observed and the prostate index (PI) was calculated. The thermal pain threshold was collected after each therapeutic course. Histopathological changes of the prostate tissue were examined by hematoxylin-eosin staining method. The expression levels of tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß) and prostaglandin E2 (PGE2) in prostatic homogenates were measured by enzyme linked immunosorbent assay (ELISA). Moreover, the expression levels of purinergic 2X7 receptor (P2X7R), NOD-like receptor pyrin domain-containing 3 (NLRP3), caspase-1 and interleukin-18 (IL-18) mRNA were quantified by quantitative real-time polymerase chain reaction. RESULTS: Compared with control group, the PI of rats increased, and the thermal pain threshold decreased significantly in model group. The morphological structure of prostate tissues of rats in model group was severely damaged with a large number of inflammatory cells infiltration. Additionally, the levels of TNF-α, IL-1ß and PGE2 were higher, and the expressions of P2X7R, NLRP3, caspase-1 and IL-18 mRNA were higher than those in control group. After EA treatment, the PI was significantly decreased, the thermal pain threshold was significantly increased, and the tissue damage was significantly improved. The expressions of inflammatory cytokines were lower in EA group, and expression of P2X7R/NLRP3 pathway was down-regulated. CONCLUSION: The effect of EA at Guanyuan (CV4), Zhongji (CV3), Huiyang (BL35) and Sanyinjiao (SP6) can improve inflammation and pain symptoms of CPPS rats induced by Complete Freund's adjuvant (CFA). This suggests that EA at Guanyuan (CV4), Zhongji (CV3), Huiyang (BL35) and Sanyinjiao (SP6) can produce anti-inflammatory analgesia effect by preventing the activation of P2X7R/NLRP3 signal pathway, inhibit the release of inflammatory cytokines in CPPS rats, which may provide a putative novel target for the treatment of CPPS.

Ningmitai capsules have anti-inflammatory and pain-relieving effects in the chronic prostatitis/chronic pelvic pain syndrome mouse model through systemic immunity.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) seriously affects the physical and mental health of approximately 90% of males. Due to its complex and unclear etiology, the treatment methods that are currently available for chronic prostatitis/chronic pelvic pain syndrome are controversial, and their efficacy is unsatisfactory. At present, most researchers believe that this kind of prostatitis is caused by autoimmune inflammation. Chinese herbs, which are the essence of traditional Chinese medicine (TCM), are emerging treatment options for inflammation and immune diseases. In this experiment, we investigated the effect of Ningmitai capsules (a kind of traditional Chinese medicine widely used to treat lower urinary tract inflammation and pain in males) on chronic prostatitis/chronic pelvic pain syndrome in a non-obese diabetes-experimental autoimmune prostatitis (NOD-EAP) mouse model. First, by using bioinformatics analysis of data from the Encyclopedia of Traditional Chinese Medicine (ETCM) database, we found that quercetin, which is one of the main components of Ningmitai capsules, could reduce the secretion of CCL2 by inhibiting the MAPK pathway. In animal experiments, it was found that after Ningmitai treatment, the inflammation in mouse prostates was alleviated, the expression of CCL2, which is related to pain, and MAPK pathway components were downregulated, and the activation of the inflammatory NF-κB and STAT3 pathways was reduced. Pelvic pain and inflammation were relieved in mice with EAP. Due to the presence of the blood-prostate barrier, the drug may not completely reach the prostate directly and take effect locally. However, we found that after Ningmitai treatment, the proportions of proinflammatory CD11b+Ly6Chigh immune cells in the spleen, bloodstream (systemic immunity), and prostate (local immunity) were reduced. The infiltration of CD11b+ immune cells into the spleen and prostate was decreased. These findings suggested that Ningmitai can treat chronic prostatitis/chronic pelvic pain syndrome by affecting systemic and local immunities through the CCL2-MAPK pathway.

Effect of electroacupuncture on cyclic adenosine monophosphate-protein kinase A-vanillic acid receptor subtype 1 of the transient receptor potential/PLK-protein kinase C-vanillic acid receptor subtype 1 of the transient receptor potential pathway based on RNA-seq analysis in prostate tissue in rats with chronic prostatitis/chronic pelvic pain syndrome.

Objective: To investigate the analgesic mechanism of electroacupuncture (EA) in rats with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Methods: Thirty male SD rats were randomly divided into sham group, model group and EA group, with ten rats in each group. The CP/CPPS model was prepared by injecting 50 µL of complete Freund's adjuvant (CFA) into the ventral lobes of the prostate tissue, and the sham group was injected with the same dose of saline. After 14 days of modeling, EA was applied to Guanyuan (CV4), Zhongji (CV3), Sanyinjiao (SP6) and Huiyang (BL35) in the EA group. After four courses, H&E staining was performed to observe the prostate tissue morphology, transcriptome sequencing (RNA-Seq) was performed for each group, and the selected signaling pathways were verified by qRT-PCR. Results: The RNA-Seq analysis results suggested that the analgesic effect of EA on CP/CPPS may be achieved by regulating prostate gene expression, which may be related to multiple biological processes and signaling pathways. qRT-PCR results showed that the vanillic acid receptor subtype 1 of the transient receptor potential (TRPV1), phospholipase C (PLC), protein kinase C (PKC), cyclic adenosine monophosphate (cAMP), and protein kinase A (PKA) were all upregulated in the model group compared to the sham group (p < 0.01). Compared with the model group, TRPV1, PLC, PKC, cAMP, and PKA were all downregulated in the EA group (p < 0.05, p < 0.01). Conclusion: The analgesic mechanism of EA on CP/CPPS may be achieved through modulation of cAMP-PKA-TRPV1/PLC-PKC-TRPV1 signaling pathway.

Clinical Review of Neuromusculoskeletal Complementary and Alternative Approaches for the Treatment of Chronic Pelvic Pain Syndrome.

Chronic pelvic pain syndrome (CPPS) is a functional pain disorder characterized by ongoing pain in the apparent absence of clinically identifiable causes. The prevalence of functional pain disorders demonstrates the importance of adequate management of ongoing symptomatology, but due to the uncertain etiology and myriad patient presentation phenotypes, reliable treatment options are difficult to implement. New interventions involving non-pharmacological approaches to pain management have been investigated across a spectrum of clinical and pre-clinical studies. Given that conservative care such as exercise, counseling, and musculoskeletal therapy is widely recommended as first-line treatment for CPPS, an updated review of these and related methodologies are needed. Familiarizing physicians and the public with the newest evidence for complementary and alternative medicine (CAM) and other conservative care treatments will assist with the promotion of evidence-based practices in a safe and reliable manner. This review aimed to summarize the current evidence and proposed mechanisms for non-pharmacological treatment specific to CAM and management of chronic pelvic pain centered on neuromusculoskeletal focused intervention such as acupuncture, auriculotherapy, manipulation, manual therapy, myofascial release, and phototherapy. The discussion suggests that reported improvements in pelvic pain or related symptomatology may be attributed to changes in the peripheral inflammasome and somatic origins of peripheral sensitization. Robustness of the included clinical studies is discussed throughout the review, and attention is paid to delineating inclusion criteria of formally diagnosed CPPS compared to general pelvic or abdominal pain. Overall, this review consolidates the current state of evidence regarding the utilization of non-traditional interventions using CAM techniques for the management of chronic pelvic pain and recommends a future direction for the field.

Treatment with the soluble guanylate cyclase activator BAY 60-2770 normalizes bladder function in an in vivo rat model of chronic prostatitis.

BACKGROUND AND PURPOSE: Chronic pelvic pain syndrome (CPPS) is a common and bothersome condition for which no pharmacological treatment options with acceptable efficacy exist. The aim of this study was to investigate the effects of the soluble guanylate cyclase (sGC) activator BAY 60-2770 and the COX-2 inhibitor celecoxib on bladder function in a rat model of CPPS. EXPERIMENTAL APPROACH: Forty-eight male Sprague-Dawley rats were intraprostatically injected with either saline, serving as control, or zymosan, to induce prostatitis. On days 8-20, the rats were treated with either dimethylsulphoxide (DMSO; vehicle), celecoxib, BAY 60-2770 or a combination of celecoxib and BAY 60-2770. Thereafter, micturition parameters were assessed in a metabolic cage and urine samples were collected. The following day, cystometry was performed. Subsequently, the urinary bladder and prostate were removed and examined histopathologically. KEY RESULTS: Induction of prostatitis led to a significant increase of micturition frequency and corresponding decrease of volume per micturition. These alterations were ameliorated by celecoxib, and completely normalized by BAY 60-2770. Induction of prostatitis led to a significantly increased number of non-voiding contractions, decreased bladder compliance and increased voiding time. These parameters were normalized by treatment with BAY 60-2770, either alone or in combination with celecoxib. The immunohistochemical analysis showed signs of prostate inflammation, but not bladder inflammation. CONCLUSION AND IMPLICATIONS: Induction of prostatitis led to significant impairment in bladder function. These alterations could be prevented by BAY 60-2770, alone or in combination with celecoxib. This is the first study to show that sGC activators could be a promising option for the treatment of CPPS.

[Effect of electroacupuncture on pain threshold and expression of pain-related factors cyclooxygenase-2, prostaglandin E2 and ß-endorphin in rats with chronic pelvic pain syndrome].

OBJECTIVE: To explore the possible mechanism of electroacupuncture (EA) underlying improvement of chronic pelvic pain syndrome (CPPS). METHODS: Fifty SD rats were randomly divided into control, model, sham operation, EA and sham EA groups (n=10 rats in each group). The CPPS model was established by injecting complete Freund's adjuvant (CFA, 50 µL) into the ventral lobes of the prostate. EA (2 Hz/100 Hz) was applied to "Guanyuan"(CV4), "Zhongji"(CV3), "Sanyinjiao" (SP6) and "Huiyang"(BL35) once daily for 40 min, 5 days a week for 4 weeks, while rats in the sham EA group were treated with the same acupoints but without electrical stimulation. Mechanical pain threshold (MPT) and heat pain threshold (HPT) were measured before and after intervention. The body weight and prostate weight were measured and prostate index was calculated. Histopathological changes of prostate tissue were observed by HE staining. The levels of cycloxygenase-2 (COX-2), prostaglandin E2 (PGE2) and ß-endorphin (ß-EP) in prostate tissue were detected by ELISA. RESULTS: Compared with the control and sham operation groups, the MPT and HPT were significantly lower (P<0.01), and the prostate weight, prostate index, the contents of PGE2 and COX-2 were significantly increased (P<0.01), while the content of ß-EP was significantly decreased (P<0.01) in the model group. Compared with the model group, the MPT and HPT were significantly increased (P<0.01) after 3 and 4 courses of treatment, and the prostate weight, prostate index, the contents of PGE2 and COX-2 were significantly decreased (P<0.01), while the content of ß-EP was significantly increased (P<0.01) in the EA group, rather than in the sham EA group (P>0.05). CONCLUSION: EA can effectively relieve pain in CPPS rats, which may be related to its functions in down-regulating COX-2 and PGE2, and up-regulating ß-EP.

Effectiveness of Myofascial Manual Therapies in Chronic Pelvic Pain Syndrome: A Systematic Review and Meta-Analysis.

INTRODUCTION AND HYPOTHESIS: Chronic pelvic pain syndrome (CPPS) is defined as the occurrence of chronic pelvic pain (CPP) in the absence of a specific cause. People typically refer to pain associated with urological, gynaecological, and sexual dysfunction, affecting the quality of life. Therefore, we assessed the effectiveness of myofascial manual therapies (MMT) for pain and symptom impact. METHODS: A systematic review and meta-analysis were conducted. Findings were reported following the 2020 PRISMA statement. Five databases were searched for RCTs. Studies were independently assessed through a standardized form, and their internal validity was evaluated using the Cochrane risk of bias (RoB) tool. Effect sizes (ES) were calculated post-treatment, and the quality of evidence was assessed through GRADE criteria. RESULTS: Seven articles were included in the review, five of these in the meta-analysis. None of these studies were completely judged at low RoB. MMT was revealed to be not significantly superior for pain reduction [ES: -0.54 (-1.16; 0.08); p = 0.09], for symptom impact [ES: -0.37 (-0.87; 0.13); p = 0.15], and for quality of life [ES: -0.44 (-1.22, 0.33), p = 0.26] compared to standard care. The quality of evidence was "very low". Other results were presented in a qualitative synthesis. CONCLUSIONS: In patients with CPP/CPPS, MMT is not considered superior to other interventions for pain reduction and symptom impact improvements. However, a positive trend was detected, and we should find confirmation in the future. Further high-quality, double-blinded, sham-controlled RCTs are first necessary to confirm these positive effects and to improve the quality of evidence.