mMCP7, a Mouse Ortholog of δ Tryptase, Mediates Pelvic Tactile Allodynia in a Model of Chronic Pelvic Pain

Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS) is a condition that affects a large number of men and has unknown etiology. We have previously demonstrated the presence of elevated levels of mast cell tryptase in expressed prostatic secretions (EPS) of CP/CPPS patients. In a murine model of CP/CPPS, we showed tryptase and its cognate receptor PAR2 as critical to the development of pelvic pain and lower urinary tract symptoms. Here, we extend these observations to demonstrate that an isoform of tryptase called delta (δ)-tryptase, is elevated in the EPS of patients with CP/CPPS and is correlated with pelvic pain symptoms. Using an Escherichia coli (CP1) -induced murine model of CP/CPPS, we demonstrated a differential response in C57BL/6J and NOD/ShiLtJ mice, with C57BL6/J mice being resistant to an increase in pelvic tactile allodynia, despite having equivalent levels of activated mast cells in the prostate. Activated tryptase+ve mast cells were observed to be in closer apposition to PGP9.5+ve nerve fibers in the prostate stroma of NOD/ShiLtJ in comparison to C57BL/6J mice. The mouse ortholog of δ-tryptase, mouse mast cell protease 7 (mMCP7) has been reported to be unexpressed in C57BL/6J mice. We confirmed the absence of mMCP7 in the prostates of C57BL/6J and its presence in NOD/ShiLtJ mice. To evaluate a role for mMCP7 in the differential allodynia responses, we performed direct intra-urethral instillations of mMCP7 and the beta (β)-tryptase isoform ortholog, mMCP6 in the CP1-infection model. mMCP7, but not mMCP6 was able to induce an acute pelvic allodynia response in C57BL/6J mice. In-vitro studies with mMCP7 on cultured mast cells as well as dissociated primary neurons demonstrated the ability to induce differential activation of pain and inflammation associated molecules compared to mMCP6. We conclude that mMCP7, and possibility its human ortholog δ-tryptase, may play an important role in mediating the development of pelvic tactile allodynia in the mouse model of pelvic pain and in patients with CP/CPPS.

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.

Botulinum Toxin-A Injection in Chronic Pelvic Pain Syndrome Treatment: A Systematic Review and Pooled Meta-Analysis

Introduction: Pain management of patients with chronic pelvic pain syndrome (CPPS) is challenging, because pain is often refractory to conventional treatments. Botulinum toxin A (BTX-A) may represent a promising therapeutic strategy for these patients. The aim of this systematic review was to investigate the role of BTX-A in CPPS treatment. Methods: We reviewed the literature for prospective studies evaluating the use of BTX-A in the treatment of CPPS. A comprehensive search in the PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases was performed from English language articles published between January 2000 and October 2021. The primary outcome was to evaluate pain improvement in CPPS after BTX-A treatment. Pooled meta-analysis of the included studies, considering the effect of BTX-A on pain evaluated at last available follow-up compared to baseline values, was performed together with meta-regression analysis. Results: After screening 1001 records, 18 full-text manuscripts were selected, comprising 13 randomized clinical trials and five comparative studies. They covered overall 896 patients of both sexes and several subtype of CPPS (interstitial cystitis/bladder pain syndrome, chronic prostatitis/prostate pain syndrome, chronic scrotal pain, gynecological pelvic pain, myofascial pelvic pain). The clinical and methodological heterogeneity of studies included makes it difficult to do an overall estimation of the real effect of BTX-A on pain and other functional outcomes of various CPPS subtypes. However, considering pooled meta-analysis results, a benefit in pain relief was showed for BTX-A-treated patients both in the overall studies populations and in the overall cohorts of patients with CPP due to bladder, prostate, and gynecological origin. Conclusions: BTX-A could be an efficacious treatment for some specific CPPS subtypes. Higher level studies are needed to assess the efficacy and safety of BTX-A and provide objective indications for its use in CPPS management.

Rectal cream “Hem” (as suppositories) in treatment of chronic abacterial prostatitis

Chronic prostatitis is one of the most common disorders in men of reproductive age. In 5-10 % of cases, prostatitis is caused by bacterial infection. In 80-90 % of patients, bacterial agent cannot be detected, and chronic abacterial prostatitis is diagnosed per the National Institute of Health classification (NIH, 1995).Even with combination therapy using drugs of different groups, chronic prostatitis is a recurrent disorder and can lead to development of symptoms in the lower urinary tract and chronic pelvic pain syndrome decreasing patients' quality of life.Phytotherapy and beekeeping products with anti-inflammatory, pain-relieving, immunostimulating effects has a certain place in the treatment of chronic prostatitis.The study objective is to evaluate the effectiveness and safety of rectal cream “Hem” (as suppositories) manufactured by Russian company ADONIS CNPG and TM LCC in patients with chronic abacterial prostatitis.

IL-17 Exacerbates Experimental Autoimmune Prostatitis via CXCL1/CXCL2-Mediated Neutrophil Infiltration

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a poorly understood disease. Accumulating evidence suggests that autoimmune dysfunction is involved in the development of CP/CPPS. IL-17 is associated with the occurrence and development of several chronic autoimmune inflammatory diseases. However, the molecular mechanisms underlying the role of IL-17 in CP/CPPS remain unclear. Herein, we first confirmed that IL-17 was increased in the prostate tissues of experimental autoimmune prostatitis (EAP) mice. Corresponding to the increase of IL-17 in the prostate of EAP, neutrophil infiltration and the levels of CXCL1 and CXCL2 (CXC chemokine ligands 1 and 2) were also increased. Treatment of EAP mice with IL-17-neutralizing monoclonal antibody (mAb) resulted in a decreased number of infiltrated neutrophils, as well as the CXCL1 and CXCL2 level. Depletion of neutrophil by anti-Ly6G antibodies ameliorated inflammatory changes and hyperalgesia caused by EAP. Fucoidan, which could potently inhibit neutrophil migration, could also ameliorate the manifestations of EAP. Our finding suggested that IL-17 promoted the production of CXCL1 and CXCL2, which subsequently triggered neutrophil chemotaxis to prostate tissues. And fucoidan might be a potential drug for the therapy of EAP by the effectively inhibiting on neutrophil infiltration.

Mechanism of Acupuncture and Moxibustion on Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Narrative Review of Animal Studies

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a genitourinary disease commonly seen in males, with symptoms involving pelvic pain, urinary system disease, and sexual dysfunction, which seriously affects physical and mental health, and it also influences the quality of life of patients. At present, the disease’s aetiology and pathogenesis are unclear, and there is also no effective treatment for it. Acupuncture and moxibustion have been a way to CP/CPPS, showing good curative effect with advantages of safety and affordability. However, the relevant research in this field is less discussed. By adopting databases, such as CNKI, VIP, Wanfang, PubMed, and Medline, this review article used keywords including chronic prostatitis, chronic pelvic pain syndrome, and electric acupuncture, manual acupuncture, moxibustion, and animal experiments, rats, mice, and mechanism research and reviewing research papers published from 1998 to 2021. Then, it further summarized and evaluated the mechanism research and gave a brief comment about modeling methods, acupoints selection, and stimulus parameters that have been used in the selected research papers. Equally important, this review article proposes a reference for the in-depth study of the mechanism of acupuncture and moxibustion on CP/CPPS and provides a theoretical basis to better treat the disease in the clinic.

Physiotherapy and combined cognitive-behavioural therapy for patients with chronic pelvic pain syndrome: results of a non-randomised controlled feasibility trial

ObjectiveTo explore feasibility in terms of delivering and evaluating a combination of physiotherapy and psychotherapy for patients with chronic pelvic pain syndrome (CPPS).DesignProspective non-randomised controlled pilot study.SettingTertiary care facility with a specialised interdisciplinary outpatient clinic for patients with CPPS.ParticipantsA total of 311 patients was approached; 60 participated. 36 patients were included in the intervention group (mean age ±SD 48.6 years±14.8; 52.8% female) and 24 in the control group (mean age ±SD 50.6 years±14.5; 58.3% female). Fourteen participants were lost to follow-up.InterventionsParticipants were non-randomly allocated to the intervention group with two consecutive treatment modules (physiotherapy and cognitive behavioural therapy) with a duration of 9 weeks each or to the control group (treatment as usual).Main outcome measuresFeasibility was operationalised in terms of delivering and evaluating the therapeutic combination. Regarding eligibility as the first aspect of feasibility, willingness to participate, dropout and satisfaction were assessed; for the second aspect, standardised self-report questionnaires measuring health-related quality of life, depression severity and pain were applied.ResultsAlthough eligibility and willingness-to-participate rates were low, satisfaction of the participants in the intervention group was high and dropout rates were low. Results indicated a small and non-significant intervention effect in health-related quality of life and significant effects regarding depression severity and pain.ConclusionsThe combination of physiotherapy and psychotherapy for patients with CPPS seems to be feasible and potentially promising with regard to effect. However, a subsequent fully powered randomised controlled trial is needed.Trial registration numberGerman Clinical Trials Register (DRKS00009976) and ISRCTN (ISRCTN43221600).