Involvement of NOTCH1-mediated Microglia Activation in Neuromodulation of Chronic Prostatitis-related Pain.

BACKGROUND/AIM: This study aimed to investigate the role of NOTCH receptor 1 (NOTCH1)-mediated activation of microglia in the L5-S2 spinal dorsal horn in chronic prostatitis pain. MATERIALS AND METHODS: Rats were divided into chronic prostatitis (CP) group and control group. Complete Freund's adjuvant was injected into the prostate, and prostate pathology and pain-related behavior were monitored to assess the successful establishment of the CP-related pain model. The dorsal horn of the L5-S2 spinal cord was collected for the detection of ionized calcium-binding adapter molecule 1 (IBA-1) and NOTCH1 expression by quantitative real time polymerase chain reaction and the detection of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) by enzyme-linked immunosorbent assay. Electrical excitability was assessed with whole-cell patch clamp. In addition, NOTCH1 receptor inhibitor or inhibitor of microglial cell activation was injected into the subarachnoid space, and the pro-inflammatory cytokines in the spinal cord were detected. RESULTS: In the CP group, the expression of NOTCH1, IBA-1, TNF-α and IL-1ß began to increase at 4 days, peaked at 12 days, and began to decline at 24 days, and it was significantly higher than in the control group (p<0.01). Inhibition of microglia or NOTCH1 receptor markedly reduced the content of TNF-α and IL-1ß in the spinal cord (p<0.05). At 4, 12 and 24 days, the amplitude and frequency of neuronal action potential increased and the threshold decreased markedly as compared to the control group (p<0.05), and spontaneous action potential was noted. CONCLUSION: NOTCH1 mediates the activation of microglia in the L5-S2 spinal cord, leading to the secretion of inflammatory factors and enhanced electrical excitability of neurons, which is related to persistent and refractory chronic prostatitis-related pain.

Urologic Chronic Pelvic Pain Syndrome Flares: A Comprehensive, Systematic Review and Meta-Analysis of the Peer-Reviewed Flare Literature.

PURPOSE: We sought to systematically review and summarize the peer-reviewed literature on urologic chronic pelvic pain syndrome flares, including their terminology, manifestation, perceived triggers, management and prevention strategies, impact on quality of life, and insights into pathophysiologic mechanisms, as a foundation for future empirical research. MATERIALS AND METHODS: We searched 6 medical databases for articles related to any aspect of symptom exacerbations for interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome. A total of 1486 abstracts and 398 full-text articles were reviewed, and data were extracted by at least 2 individuals. RESULTS: Overall, we identified 59 articles, including 36 qualitative, cross-sectional, or case-control; 15 cohort-based; and 8 experimental articles. The majority of studies described North American patients with confirmed diagnoses. "Flare" was a commonly used term, but additional terminology (eg, exacerbation) was also used. Most flares involved significant increases in pain intensity, but less data were available on flare frequency and duration. Painful, frequent, long-lasting, and unpredictable flares were highly impactful, even over and above participants' nonflare symptoms. A large number of perceived triggers (eg, diet, stress) and management/prevention strategies (eg, analgesics, thermal therapy, rest) were proposed by participants, but few had empirical support. In addition, few studies explored underlying biologic mechanisms. CONCLUSIONS: Overall, we found that flares are painful and impactful, but otherwise poorly understood in terms of manifestation (frequency and duration), triggers, treatment, prevention, and pathophysiology. These summary findings provide a foundation for future flare-related research and highlight gaps that warrant additional empirical studies.

[Effect of electroacupuncture on the morphology of prostate and degranulation of mast cells in rats with chronic nonbacterial prostatitis].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the morphology of prostate and degranulation of mast cells in prostate of rats with chronic nonbacterial prostatitis (CNP). METHODS: Male SD rats were randomly divided into sham operation group, model group and EA group, with 8 rats in each group. CNP model was established by surgical castration combined with 17-ß estradiol injection once daily for 30 days. EA was applied to "Zhongji" (CV3), "Guanyuan" (CV4) and bilateral "Dahe" (KI12) for 20 min, once daily for 8 days. The mechanical pain threshold of scrotum skin area was tested before modeling, after modeling and after intervention. The pathological morphology of the prostate was observed by HE staining. Collagenous fiber was observed by Masson staining. The infiltration of mast cells was observed by toluidine blue staining. The contents of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in prostate were determined by ELISA. The protein expression levels of tryptase and transforming growth factor ß1 (TGF-ß1) in prostate were detected by Western blot. RESULTS: A normal appearance with little inflammatory cell infiltration was observed in the prostate of the sham operation group. Gland atrophy, epithelial destruction, hyperemia and edema, diffuse inflammatory cell infiltration and visible collagen fiber deposition were observed in prostate of the model group. The degree of infiltration of inflammatory cells and collagen fiber deposition were reduced in the EA group. Compared with the sham operation group, mechanical pain threshold was decreased (P<0.01), while the collagen volu-me fraction (CVF) of prostate, the degranulated rate of mast cells, the protein expression levels of tryptase and TGF-ß1, and the contents of IL-6 and TNF-α were increased (P<0.01) in the model group. Following EA intervention, compared with the model group, the mechanical pain threshold was increased (P<0.01), CVF of the prostate, the degranulated rate of mast cells, the protein expression levels of tryptase and TGF-ß1, and the contents of IL-6 and TNF-α were decreased (P<0.05, P<0.01) in the EA group. CONCLUSION: EA can relieve pain and reduce inflammation and fibrosis of prostate in CNP rats, which may be related to inhibiting the degranulation of prostate mast cells and down-regulating the expression of inflammatory factors and TGF-ß1.

Low-Energy Shock Wave Suppresses Prostatic Pain and Inflammation by Modulating Mitochondrial Dynamics Regulators on a Carrageenan-Induced Prostatitis Model in Rats.

A low-energy shock wave (LESW) has therapeutic effects on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS); however, its mechanism of action remains unclear. We explored the effects of LESW on the prostate and mitochondrial dynamics regulators in a rat model of carrageenan-induced prostatitis. The imbalance of mitochondrial dynamics regulators may affect the inflammatory process and molecules and contribute to CP/CPPS. Male Sprague-Dawley rats received intraprostatic 3% or 5% carrageenan injections. The 5% carrageenan group also received LESW treatment at 24 h, 7 days, and 8 days. Pain behavior was evaluated at baseline, 1 week, and 2 weeks after a saline or carrageenan injection. The bladder and the prostate were harvested for immunohistochemistry and quantitative reverse-transcription polymerase chain reaction analysis. Intraprostatic carrageenan injection induced inflammatory reaction in the prostate and the bladder, decreased the pain threshold, and resulted in the upregulation of Drp-1, MFN-2, NLRP3 (mitochondrial integrity markers), substance P, and CGRP-RCP, whose effects were maintained for 1-2 weeks. LESW treatment suppressed carrageenan-induced prostatic pain, inflammatory reaction, mitochondrial integrity markers, and expression of sensory molecules. These findings support a link between the anti-neuroinflammatory effects of LESW in CP/CPPS and the reversal of cellular perturbations caused by imbalances in mitochondrial dynamics in the prostate.

Nutritional and surgical aspects in prostate disorders.

Prostate disorders are commonplace in medicine, especially in older men, with prostatitis, benign prostatic hyperplasia, and prostate cancer being the most abundant pathologies. The complexity of this organ, however, turns treatment into a challenge. In this review, we aim to provide insight into the efficacy of alternative treatments, which are not normally used in conventional medicine, with a particular focus on nutrients. In order to understand why and how nutrition can be beneficial in diseases of the prostate, we give an overview of the known characteristics and features of this organ. Then, we provide a summary of the most prevalent prostate illnesses. Finally, we propose nutrition-based treatment in each of these prostate problems, based on in-depth research concerning its effects in this context, with an emphasis on surgery. Overall, we plead for an upgrade of this form of alternative treatment to a fully recognized mode of therapy for the prostate.

Study protocol and methods for Easing Pelvic Pain Interventions Clinical Research Program (EPPIC): a randomized clinical trial of brief, low-intensity, transdiagnostic cognitive behavioral therapy vs education/support for urologic chronic pelvic pain syndrome (UCPPS).

BACKGROUND: Urologic chronic pelvic pain syndrome (UCPPS) encompasses several common, costly, diagnoses including interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome that are poorly understood and inadequately treated with conventional medical therapies. Behavioral strategies, recommended as a first-line treatment for managing symptoms, are largely inaccessible, time and labor intensive, and technically complex. The Easing Pelvic Pain Interventions Clinical Research Program (EPPIC) is a clinical trial examining the efficacy of low-intensity cognitive behavioral therapy (Minimal Contact CBT or MC-CBT) for UCPPS and its durability 3 and 6 months post treatment. Additional aims include characterizing the operative processes (e.g., cognitive distancing, context sensitivity, coping flexibility, repetitive negative thought) that drive MC-CBT-induced symptom relief and pre-treatment patient variables that moderate differential response. METHODS: UCPPS patients (240) ages 18-70 years, any gender, ethnicity, and race, will be randomized to 4-session MC-CBT or a credible, non-specific education comparator (EDU) that controls for the generic effects from simply going to treatment. Efficacy assessments will be administered at pre-treatment, 2 weeks, and 3 and 6 months post treatment-week acute phase. A novel statistical approach applied to micro-analytic mediator assessment schedule will permit the specification of the most effective CBT component(s) that drive symptom relief. DISCUSSION: Empirical validation of a low-intensity self-management therapy transdiagnostic in scope has the potential to improve the health of chronic pelvic pain patients refractory to medical therapies, reduce social and economic costs, conserve health care resources, as well as inform evidence-based practice guidelines. Identification of change mechanisms and moderators of treatment effects can provide proactive patient-treatment matching fundamental to goals of personalized medicine. TRIAL REGISTRATION: Clinicaltrials.gov NCT05127616. Registered on 9/19/21.

[Clinical study of type â ¢ prostatitis treated with "warming and promoting technique" of acupuncture combined with extracorporeal shock wave].

OBJECTIVE: To observe the clinical curative effect of wentongzhenfa (warming and promoting technique of acupuncture) combined with extracorporeal shock wave in treatment of type Ⅲ prostatitis. METHODS: A total of 96 patients with type Ⅲ prostatitis were randomly divided into an observation group (48 cases) and a control group (48 cases). In the control group, the extracorporeal shock wave was combined with even-needling technique of acupuncture at Guanyuan (CV4), Mingmen (GV4), Zhongji (CV3), Zusanli (ST36), etc. In the observation group, the extracorporeal shock wave was combined with "warming and promoting technique" of acupuncture at the same acupoints as the control group. The treatment lasted 30 min each time, once daily in either group. There were 2 days of interval after consecutive treatment for 5 days. Totally, the duration of treatment was 1 month in two groups. The clinical curative effect was assessed after treatment. Before and after treatment, the changes in the concentrations of tumor nerosis factor-α (TNF-α), interleukin-1ß(IL-1ß) and IL-6 in prostatic fluid were determined; and the symptoms were scored, i.e. frequent, urgent and burning painful urine, difficulty in urination, dribbling urine, distending pain in perineum, bitter taste and dry mouth, and scrotal dampness. The changes in the scores of National Institute of Health chronic prostatitis symptom index (NIH-CPSI), international index of erectile function (IIEF), visual analogue scale (VAS) were evaluated befroe and after treatment. Successively, before treatment, after treatment, as well as 1 and 3 months after treatment, the quality of life was evaluated by Karnofsky in the patients of two groups. RESULTS: After treatment, the total effective rate was 89.6% (43/48) in the observation group, higher than 70.8% (34/48) in the control group (P<0.05). Compared with those before treatment, the concentrations of TNF-α and IL-1ß in the prostatic fluid were all decreased (P<0.05) and the concentration of IL-6 was increased (P<0.05), the scores of symptoms, NIH-CPSI, IIEF and VAS were all reduced (P<0.05) in two groups. The changes of the above indexes were more obvious in the observation group than those in the control group (P<0.05). After treatment and 1 and 3 months after treatment, Karnofsky scores all increased (P<0.05) in two groups，and the increases were more significant in the observation group (P<0.05). CONCLUSION: "Warming and promoting technique" of acupuncture combined with extracorporeal shock wave promotes the elimination of local inflammatory factors, relieves clinical symptoms, improves the quality of life, as well as has a satisfactory short-term and medium-term curative effect on type Ⅲ prostatitis.

Therapeutic interventions to urologic chronic pelvic pain syndrome and UPOINT system for clinical phenotyping: How far are we?

The assessment and management of urologic chronic pelvic pain syndrome (UCPPS), is controversial. It is classified by voiding symptoms, pelvic pain, and bladder pain, which is weekly treated, weekly understood, and bothersome. In the aspect of clinical efforts and research to help people with this syndrome have been hampered by the deficiency of a widely reliable, accepted, and a valuable tool to evaluate the patient symptoms and quality of life (QoL) impact. However, the etiology comes into sight is multifactorial, and available treatment options have been imprecise considerably in present years. We compiled the published literature on the assessment of the syndrome, a tentative role of pharmacological and non-pharmacological (conservative, alternative, and invasive therapy) interventions in eradicating the disease as well as improving symptoms. The previously published literature on animal models has established the association of immune systems in the etiology, pathogenesis, and progression of the disease. The UPOINT system for clinical phenotyping of UCPPS patients has six predefined domains that direct multimodal therapy, which would lead to significant symptom improvement in the medical field. The narrative review aims to scrutinize the fluctuating scientist's views on the evaluation of patient and multimodal treatment of the UPOINT system.

Outcomes and clinical predictors of extracorporeal shock wave therapy in the treatment of chronic prostatitis/chronic pelvic pain syndrome: a prospective randomized double-blind placebo-controlled clinical trial.

OBJECTIVES: To report the one-year results of ESWT on CPPS patients and the possible clinical characteristics that may affect its efficacy. PATIENTS & METHODS: A prospective randomized clinical study between January 2017 and January 2021 on 155 adult patients with chronic pelvic pain syndrome. All patients were initially evaluated with a thorough history and physical examination. Baseline symptoms evaluation of each participant was assessed using NIH-CPSI score, IPSS, VAS, and IIEF-5 score. Patients were randomized into two groups: a verum treatment group and a placebo treatment group. Patients of verum group in the lithotomy position received a perineally applied ESWT treatment once a week for four weeks with 3000 impulses each. Patients of placebo group received the same therapy head of the same device with a layer of air-filled microspheres to absorb the shock waves. The previously mentioned validated scores were reassessed on regular follow-up visits at one, three, six, and 12 months after the completion of ESWT. RESULTS: A statistically significant improvement was noticed in the mean values of NIH-CPSI, IPSS, VAS, and IIEF-5 of the patients of verum group over the follow-up period with also statistically significant difference between both groups. At the first visit of follow-up after ESWT, 63 (82.8%) patients had ≥6 points decrease in the NIH-CPSI total score, while 13 (17.2%) patients did not. Univariate and multivariate analyses of the clinical characteristics between the responders and non-responders showed that those patients with history of psychological disorders or had higher initial NIH-CPSI score had a significantly lower response rate to ESWT (p = 0.005, 0.02 & p = 0.002, 0.004 respectively). ROC curve of NIH-CPSI score showed that a score of 32 was the cut-off point above which the response to ESWT decreased. CONCLUSION: ESWT is an effective treatment option for CPPS. Its efficacy remained throughout long-term follow up. High initial NIH-CPSI score and history of psychological problems are significant predictors for it.

The Effect of Low-intensity Shockwave Therapy on Non-neurogenic Lower Urinary Tract Symptoms: A Systematic Review and Meta-analysis of Preclinical and Clinical Studies.

CONTEXT: Low-intensity shockwave therapy (LiST) has emerged as an effective treatment for pain in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), and it has been postulated that LiST may also be effective in patients with lower urinary tract symptoms (LUTS). OBJECTIVE: To perform a systematic review and meta-analysis of experimental and clinical studies exploring the effect of LiST on LUTS in an attempt to provide clinical implications for future research. EVIDENCE ACQUISITION: We systematically searched PubMed, Cochrane Library, and Scopus databases from inception to March 2021 for relevant studies. We provided a qualitative synthesis regarding the role of LiST in LUTS and performed a single-arm, random-effect meta-analysis to assess the absolute effect of LiST on LUTS only in patients with CP/CPPS (PROSPERO: CRD42021238281). EVIDENCE SYNTHESIS: We included 23 studies (11 experimental studies, seven nonrandomized controlled trials [non-RCTs], and five RCTs) in the systematic review and seven in the meta-analysis. All experimental studies were performed on rats with LUTS, and the clinical studies recruited a total of 539 participants. In patients with CP/CPPS, the absolute effect of LiST on maximum flow rate and postvoid residual was clinically insignificant. However, the available studies suggest that LiST is effective for the management of pain in patients with either CP/CPPS or interstitial cystitis/bladder pain syndrome. Additionally, LiST after intravesical instillation of botulinum neurotoxin type A may enhance its absorption and substitute botulinum neurotoxin type A injections in patients with overactive bladder. Furthermore, the available evidence is inconclusive about the role of LiST in patients with benign prostatic obstruction, stress urinary incontinence, or underactive bladder/detrusor hypoactivity. CONCLUSIONS: LiST may be effective for some disorders causing LUTS. Still, further studies on the matter are necessary, since the available evidence is scarce. PATIENT SUMMARY: Low-intensity shockwave therapy represents a safe, easily applied, indolent, and repeatable on an outpatient basis treatment modality that may improve lower urinary tract symptoms.

Intraprostatic injection of exosomes isolated from adipose-derived mesenchymal stem cells for the treatment of chronic non-bacterial prostatitis.

Mesenchymal stem cells (MSCs) own the capacity to secrete trophic factors as exosomes which play significant roles in regulating the functions of other cells and preventing inflammation. Due to the inflammatory process in chronic non-bacterial prostatitis (CNP) and the ambiguity in the treatment of this disease, the present study was aimed to investigate the therapeutic use of adipose-derived MSC exosomes in an animal model of CNP. MSCs were first isolated from rat subcutaneous adipose tissue, and exosomes were extracted from them. Specific features of exosomes were characterized by a scanning electron microscope, western blot technique, and Dynamic Light Scattering methods. To establish CNP in rats, intraprostatic injection of Freund's complete adjuvant was done. After confirmation of prostatitis, intraprostatic injections of exosomes were performed for treatment. Histological evaluation revealed that treatment with exosomes resulted in a relative improvement of lesions caused by CNP. The expression of p-NF-κB and p-IκBα proteins along with inflammatory markers was significantly increased in the CNP group, which treatment with exosomes significantly reduced their expression as well as IL-1ß and TNF-α proteins. The antioxidant effects of exosomes were also determined by significantly regulating glutathione peroxidase and superoxide dismutase activity and malondialdehyde levels in these animals. Our results cautiously suggest the therapeutic effects of MSC-derived exosomes against CNP-induced prostatitis through their antioxidant and anti-inflammatory activities, which should be further considered in the future.

IL-1ß-primed mesenchymal stromal cells exert enhanced therapeutic effects to alleviate Chronic Prostatitis/Chronic Pelvic Pain Syndrome through systemic immunity.

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) seriously affects patient health. Despite the elusiveness of innate therapeutic effects, mesenchymal stromal cells (MSCs) hold great promise for inflammation-related diseases. Recent evidence indicates that disease-specific inflammatory cytokines could enhance the therapeutic effects of MSCs. METHODS: By establishing a CP/CPPS mouse model and pretreating MSCs with the cytokine interleukin-1ß (IL-1ß), we studied the IL-1ß-primed MSC immunoregulatory ability and targeted migration ability in vitro and in CP/CPPS mice. RESULTS: IL-1ß levels significantly increased in the prostate tissue and serum of experimental autoimmune prostatitis (EAP) mice. Pretreatment with IL-1ß enhanced the immunomodulatory potential and targeted migration of MSCs in vitro. Furthermore, intravenous infusion of IL-1ß-primed MSCs dampened inflammation in prostate tissues and alleviated hyperalgesia in EAP mice. The infused MSCs inhibited monocyte infiltration and promoted regulatory T lymphocyte formation in prostate tissue, thus remodeling the local environment. Surprisingly, IL-1ß-primed MSCs exhibited improved accumulation in the spleen but not in prostate tissue. Accordingly, infused MSCs reshaped systemic immunity by reducing the proportion of Ly6ChighCD11b+ monocytes and boosting the proportion of CD4+Foxp3+ regulatory T lymphocytes in the spleen and lung. Inflammatory chemokine (C-C motif) ligand 2 (CCL2) decreased through the downregulation of the NF-κB and JNK/MAPK pathways by inflammatory resolution via MSCs infusion to alleviate pain. CONCLUSION: In summary, IL-1ß-primed MSCs restored systemic immunologic homeostasis to alleviate CP/CPPS by modulating systemic immunity. These findings provide a novel strategy to boost the therapeutic effects of MSC-based therapy for CP/CPPS and reveal the essential role of systematic immunity in the treatment of CP/CPPS with MSC infusion.

Research trends of prostatitis over past 20 years: A bibliometric analysis.

In the past two decades, thousands of documents in the field of prostatitis have been published. This bibliometric analysis aimed to assess the characteristics, hotspots and frontiers trend of global scientific output on prostatitis. With the trend of moderate growth, altogether 2,423 papers were reviewed. The leading role of the United States in global prostatitis research was obvious, while China had developed rapidly in recent years. Queen's University and JOURNAL OF UROLOGY were the most prolific affiliation and journal respectively. Nickel, J. C made the greatest contribution to the field of prostatitis. Five hotspots have been confirmed: (a) male infertility associated with prostatitis and the molecular mechanisms; (b) diagnosis and treatment of prostatitis; (c) inflammation, pain and bladder irritation symptoms; (d) relationship between chronic prostatitis/chronic pelvic pain syndrome, benign prostatic hyperplasia and prostate cancer; (e) epidemiology, complications of prostatitis and improvement of acupuncture. This bibliometric analysis reveals that the international cooperation was becoming more and more close. Hotspot analysis shows that the molecular mechanism of prostatitis will be a hotspot in the future, mainly focussing on inflammatory immunity and oxidative stress.

Li-ESWT treatment reduces inflammation, oxidative stress, and pain via the PI3K/AKT/FOXO1 pathway in autoimmune prostatitis rat models.

BACKGROUND: Due to limited data on the pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and the suboptimal therapeutic effect, the development of new and effective treatment modalities was needed urgently. Low-intensity extracorporeal shock wave therapy (Li-ESWT) has been reported for the treatment of CP/CPPS. However, the underlying mechanism remains to be elucidated. OBJECTIVE: To interrogated the efficacy and the mechanism of Li-ESWT in the treatment of CP/CPPS. MATERIALS AND METHODS: According to different treatments, RWPE-1 cells (human prostate epithelial cells) were randomly divided into three groups: control group, LPS (lipopolysaccharide) group, or Li-ESWT group (LPS-induced RWPE-1 managed by Li-ESWT). Following the Li-ESWT treatment, the levels of oxidative stress were assayed. We then established a rat model of experimental autoimmune prostatitis (EAP) by injecting prostatic protein homogenate mixed with complete Freund's adjuvant. The Sprague-Dawley rats were randomly divided into the control group, EAP group, or Li-ESWT group. Von Frey Filament was used to quantify pelvic hyperalgesia in the rats. Prostates tissues from each group were collected for immunohistochemistry, oxidation stress, and Western blot analysis. RESULTS: Histological analysis showed reduced inflammation and expression of cytokines (TNF-α, IL-1ß, IL-6, COX-2, SP) in prostate tissues from the Li-ESWT group compared with those from the EAP group (all p < 0.05). Similarly, there was reduced pelvic pain and allergic symptoms in the Li-ESWT group compared with the EAP group (all p < 0.05). Besides, Li-ESWT treatment could decrease oxidative stress in the prostate and in RWPE-1 cells, respectively (both p < 0.05). Moreover, the Li-ESWT upregulated the expression of CAT through the inhibition of phosphorylation of AKT/FOXO1 signaling pathway. DISCUSSION AND CONCLUSIONS: Li-ESWT may reduce inflammation, oxidative stress, and pain in rats with autoimmunity-induced prostatitis via the PI3 K/AKT/FOXO1 pathway. It implies that Li-ESWT can present a potential therapeutic option for the treatment of CP/CPPS.

Extracellular vesicles released from hiPSC-derived MSCs attenuate chronic prostatitis/chronic pelvic pain syndrome in rats by immunoregulation.

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is an intractable nonbacterial inflammatory disease. Mesenchymal stem cells (MSCs) derived from human induced pluripotent stem cells (hiPSCs, iMSCs) have been well documented for the management of inflammatory and autoimmune disorders because of their powerful immunoregulatory and anti-inflammatory capacities. Recently, studies have indicated that extracellular vesicles (EVs) released from iMSCs hold biological functions similar to their parental cells. This study aimed to evaluate the therapeutic efficacy of EVs released from iMSCs (iMSCs-EVs) on CP/CPPS and to explore the underlying mechanisms. METHODS: An experimental autoimmune prostatitis (EAP) model was established in rats by subcutaneous injection of prostate antigen with adjuvant. Then, iMSCs-EVs were injected into EAP rats via the tail vein. Pain behavioral measurements, urodynamic tests, and histopathological analyses were performed at 2, 4, and 6 weeks. The expression of cyclooxygenase-2 (COX-2) was evaluated by immunofluorescence staining and Western blot. The alterations of B cells, Th1 cells, Th2 cells, Th17 cells, and Treg cells in peripheral blood and spleen were analyzed using flow cytometry. The levels of Th1-, Th2-, Th17-, and Treg-related inflammatory mediators were determined by ELISA. RESULTS: After iMSCs-EVs administration, rats had reduced pain as indicated by the recovery of nociceptive responses to baseline. The voiding pressure was significantly reduced, and the intercontraction interval was increased. The findings of histopathological analysis revealed that iMSCs-EVs could significantly decrease inflammatory cell infiltration and promote basal lamina and glandular epithelial tissue repair. Further studies demonstrated that the overexpression of COX-2 was downregulated by iMSCs-EVs. Meanwhile, the increases in the percentages of Th1 and Th17 cells were dramatically reversed. Also, rats that received iMSCs-EVs showed markedly increased percentages of Treg cells. The levels of those inflammatory mediators showed the same changing tendency. CONCLUSIONS: iMSCs-EVs administration has the potential to ameliorate chronic pelvic pain, improve voiding dysfunction, suppress inflammatory reactions, and facilitate prostatic tissue repair. The functions are mediated by downregulating the overexpression of COX-2 and restoring the imbalance of Th1/Th2 and Treg/Th17 cells.

Evaluation of a low-intensity shockwave therapy for chronic prostatitis type IIIb/chronic pelvic pain syndrome: a double-blind randomized sham-controlled clinical trial.

BACKGROUND: Currently, there is no efficacious treatment method for chronic prostatitis type IIIb/chronic pelvic pain syndrome (CP/CPPS). Aim of the study was to investigate and compare the efficacy and safety of low-intensity shockwave therapy (LiST) vs. sham treatment in CP/CPPS patients. METHODS: Patients with CP/CPPS diagnosis were randomized in this prospective, sham-controlled, double-blind study either to the active groups (Group B, C) who received 5000 shockwaves per session with energy flux density 0.1 mJ/mm2 or to the sham group (Group A) who received 5000 shockwaves from a visually identical sham probe. All groups underwent six sessions (once/week). LiST effects on pain, micturition, quality of life (QoL), and erectile function were evaluated at 4, 12, and 24 weeks after treatment. The parameters were investigated using validated questionnaires. Uroflowmetry and post void residual calculation were performed at baseline and at 4- and 12-week FU visit. Prostate mpMRI and PSA measurement were performed at baseline and 12-week FU visit. RESULTS: Overall, 45 men were randomized to the active (n = 30) and sham groups (n = 15). Regarding impact of LiST in National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) total, pain, and QoL subdomains scores a clear and persistent in all FU timepoints improvement was found compared to sham treatment. NIH-CPSI urinary subdomain, International Prostate Symptom Score [IPSS], PSA, and mpMRI-PIRADS scores did not differ between the two groups. The mean difference between the LiST and sham group in the change of the NIH-CPSI pain-domain score (Q1-4) from baseline to 12 weeks after final treatment which was 3.3 (95% CI, 1.8, 4.7). Perineal LiST was easy and safe to perform without anesthesia or any side-effects. CONCLUSIONS: LiST seems to be a safe and effective treatment option for CP/CPPS, considerably improving pain and quality of life. Lack of any side-effects, and the potential for repetition make LiST a promising treatment choice for CP/CPPS patients.

Experimental autoimmune prostatitis: different antigens induction and antigen-specific therapy.

PURPOSE: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has uncertain etiology and lacks effective treatment. Autoimmunity is an important pathogeny, and experimental autoimmune prostatitis (EAP) models have long been used for studying CP/CPPS. This review presents the detailed current knowledge of EAP models based on evaluation criteria aspects to provide a tool for model selection in pathogenesis studies and therapeutic drug screening. METHODS: We extensively searched the published literature on CP/CPPS and different antigen-induced EAP models focusing on the histopathology, clinical-related phenotypes, and biochemical indicators. We also cover the changes in the prostate function and other organs in EAP. Finally, we try to get some insights about antigen-based therapeutic approaches for CP/CPPS. RESULTS: Several inciting autoantigens were reported in EAP, including male accessory gland extracts, prostate extracts (PE), prostatic steroid-binding protein, prostatic spermine-binding protein (p25), prostatic acid phosphatase, seminal vesicle secretory protein 2, and T2 peptide. All of these models mimicked histological prostatitis, however only p25- and T2-induced models developed both pelvic pain and voiding behaviors. PE immunization is the most widely used method. Diminished fertility and mental health disorders can be found in PE model. Oral and intravenous T2 peptide have been studied for antigen-specific therapy and achieved preliminary progress in EAP models. CONCLUSIONS: PE-induced model is the most commonly used, while T2- or p25-model could serve as a promising CP/CPPS model. Antigen-specific therapy in CP/CPPS deserves further study.

Management of Chronic Bacterial Prostatitis.

PURPOSE OF REVIEW: We conducted a review of the literature describing the most up-to-date diagnosis and treatment options of chronic bacterial prostatitis. RECENT FINDINGS: Recurrence after oral antimicrobial therapy is common, due in part to the rising rates of antimicrobial resistance and inability to completely clear the offending bacteria from the prostate following prostatitis. Recent literature has described various treatment options for chronic bacterial prostatitis refractory to conventional antimicrobial agents, including the use of alternative agents such as fosfomycin, direct antimicrobial injections into the prostate, surgical removal of infected prostatic tissue, chronic oral antibiotic suppression, and an emerging novel therapy utilizing bacteriophages to target antibiotic resistant bacteria. Management of chronic bacterial prostatitis, especially recurrence after oral antimicrobial treatment, remains challenging. This review highlights an urgent need for further evidence assessing the efficacy and safety of treatment modalities for chronic bacterial prostatitis refractory to conventional oral antimicrobials.

CHRONIC PROSTATITIS THERAPY COMBINED WITH ELECTROMYOSTIMULATION-ASPIRATION, TRANSURETHRAL ELECTROPHONOPHORESIS OF PLATELET-RICH PLASMA AND TRANSRECTAL LOW-INTENSITY PULSED ULTRASOUND.

Chronic inflammatory diseases of the prostate are one of the most common andurological nosology. This group of diseases includes heterogeneous pathology such as chronic bacterial prostatitis, chronic non-infectious prostatitis, prostate asymptomatic inflammation and chronic pelvic pain syndrome. Currently, biological and physiotherapeutic chronic prostate inflammatory diseases treatment methods are actively being studied, such as platelet rich plasma (PRP) therapy and low-intensity pulsed ultrasound (LIPUS) therapy. Aim - assessment of the efficacy of the treatment model of chronic nonspecific bacterial prostatitis which includes combined application of transurethral vacuum drainage with PRP electrophonophoresis and transrectal LIPUS of prostate gland. A prospective clinical study was conducted on a contingent of 50 patients of "Men's Health Clinic" (Kiev, Ukraine) suffering from chronic nonspecific bacterial prostatitis (ICD-10: N41.1). LIPUS and PRP combination demonstrates the further progress of the therapeutic effect in terms of difficulty urinating (p=0,04) and a subjective decrease of life quality (p≤0,01). Overall I-PSS score indicates a decrease in the overall severity to a mild level (p≤0,01). VAS level of pelvic pain shoved the significant clinical effect of LIPUS and PRP combination (p≤0,01). LIPUS and PRP combination showed efficacy in reduction of leucocytes in ejaculate (p≤0,01), normalization of semen acidity (p≤0,01) and mucus production (p≤0,01). Treatment model of chronic nonspecific bacterial prostatitis which includes combined application of transurethral vacuum drainage with PRP electrophonophoresis and transrectal LIPUS as an addition to standard antibiotic therapy had shown deep positive impact on prostate inflammation. Effects of PRP and LIPUS combined application are additive to effects of traditional interventions in general results of therapy, life quality, pain reduction and normalization of ejaculate parameters of patients with chronic prostate inflammation.

[Multidisciplinary approach in urology. Clinical aspects].

A solving diagnostic and therapeutic problems in patients with various urologic diseases often requires a cooperation between different specialists which emphasizes the interdisciplinarity of our discipline. A number of clinical manifestations and diseases that urologists have to deal with and in which they definitely need a timely assistance from other specialists are described in the article. Determining the connecting links in the work of different specialists, we tried to recall the main " intersection points" and draw attention to the necessary cooperation.