Protective effect of astaxanthin on chronic prostatitis/chronic pelvic pain syndrome in rat through modulating NF-κB signaling pathway.

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common male urological disease characterized by chronic pelvic pain and various discomforts. Astaxanthin (AST) has multiple functions, including anti-inflammatory property, but it is unclear whether AST plays a key role in CP/CPPS and how it works. This study aimed to investigate the protective effect of AST on CP/CPPS in rats and the underlying mechanism. Methods: A CP/CPPS rat model was induced by intraprostatic injection of carrageenan and the blood specimens and prostates were harvested for further research after oral administration of AST for 4 weeks. Results: Tactile allodynia test showed that AST ameliorated chronic pelvic pain in a dose-depended manner. In addition, histological evaluation indicated that AST alleviated CP/CPPS rat prostate histological inflammation. Meanwhile, AST suppressed the expression of proinflammatory cytokines, including interleukin-1ß (IL-1ß), IL-6, IL-8, and tumor necrosis factor-α (TNF-α). Besides, AST inhibited the activities of prostaglandin E2 (PGE2) and cyclooxygenase 2 (COX2). Furthermore, AST decreased the activation of the nuclear factor-κB (NF-κB) signaling pathway. Conclusions: Our study has shown that AST exerts an anti-inflammatory and protective effect against CP/CPPS and the function is mediated at least through the suppression of NF-κB signaling pathway. These results provide evidence of AST as the potential agents for the treatment of CP/CPPS.

Characterization of prostatic cancer lesion and gleason grade using a continuous-time random-walk diffusion model at high b-values.

Background: Distinguishing between prostatic cancer (PCa) and chronic prostatitis (CP) is sometimes challenging, and Gleason grading is strongly associated with prognosis in PCa. The continuous-time random-walk diffusion (CTRW) model has shown potential in distinguishing between PCa and CP as well as predicting Gleason grading. Purpose: This study aimed to quantify the CTRW parameters (α, ß & Dm) and apparent diffusion coefficient (ADC) of PCa and CP tissues; and then assess the diagnostic value of CTRW and ADC parameters in differentiating CP from PCa and low-grade PCa from high-grade PCa lesions. Study type: Retrospective (retrospective analysis using prospective designed data). Population: Thirty-one PCa patients undergoing prostatectomy (mean age 74 years, range 64-91 years), and thirty CP patients undergoing prostate needle biopsies (mean age 68 years, range 46-79 years). Field strength/Sequence: MRI scans on a 3.0T scanner (uMR790, United Imaging Healthcare, Shanghai, China). DWI were acquired with 12 b-values (0, 50, 100, 150, 200, 500, 800, 1200, 1500, 2000, 2500, 3000 s/mm2). Assessment: CTRW parameters and ADC were quantified in PCa and CP lesions. Statistical tests: The Mann-Whitney U test was used to evaluate the differences in CTRW parameters and ADC between PCa and CP, high-grade PCa, and low-grade PCa. Spearman's correlation of the pathologic grading group (GG) with CTRW parameters and ADC was evaluated. The usefulness of CTRW parameters, ADC, and their combinations (Dm, α and ß; Dm, α, ß, and ADC) to differentiate PCa from CP and high-grade PCa from low-grade PCa was determined by logistic regression and receiver operating characteristic curve (ROC) analysis. Delong test was used to compare the differences among AUCs. Results: Significant differences were found for the CTRW parameters (α, Dm) between CP and PCa (all P<0.001), high-grade PCa, and low-grade PCa (α:P=0.024, Dm:P=0.021). GG is correlated with certain CTRW parameters and ADC(α:P<0.001,r=-0.795; Dm:P<0.001,r=-0.762;ADC:P<0.001,r=-0.790). Moreover, CTRW parameters (α, ß, Dm) combined with ADC showed the best diagnostic efficacy for distinguishing between PCa and CP as well as predicting Gleason grading. The differences among AUCs of ADC, CTRW parameters and their combinations were not statistically significant (P=0.051-0.526). Conclusion: CTRW parameters α and Dm, as well as their combination were beneficial to distinguish between CA and PCa, low-grade PCa and high-grade PCa lesions, and CTRW parameters and ADC had comparable diagnostic performance.

Pubourethral and uterosacral male analogues suggest parallel male/female pelvic anatomy and symptom pathogenesis.

The thesis that functional/dysfunctional male/female pelvic floor anatomy are parallel, originated from two studies: a successful retropubic perineal male sling for post-prostatectomy stress urinary incontinence (SUI) and discovery of a male uterosacral ligament (USL) analogue, we named "prostatosacral ligament" (PSL). In 25 out of the studied 27 males (92.6%), it starts on both sides of the median sulcus of the prostate the ligament passes lateral to the rectum being fused with the lateral margin of the mesorectum before leaving it as it thins out to be attached posteriorly similar to the USL. The ultrasound data during straining in men and women showed the same three oppositely acting muscle vectors contracting around analogous ligaments, puboprostatic ligament (PPL) (male), and pubourethral ligament (PUL) (female). Further parallels were pubovesical ligaments (PVLs) and arc of Gilvernet as part of the continence and micturition mechanisms. Impressive evidence for parallel anatomy came from the successful cure of 22 males with post-prostatectomy SUI using a perineal retropubic tissue fixation system (TFS) minisling applied to the PPL using a similar methodology to that used in the female for PUL midurethral sling repair for cure of SUI. Laparoscopic evidence confirmed the prostate as a male analogue of the cervix, and PSLs as analogues of USLs: PSL origin from the prostate attached laterally to the mesorectum and inserted into the sacrum. Histologically, PSLs had identical features with USLs: collagen, elastin, smooth muscle, blood vessels and nerves. Virtually identical symptoms for "chronic prostatitis" (CP) and "posterior fornix syndrome" (PFS), such as chronic pelvic pain, overactive bladder (OAB), abnormal emptying, gave birth to the hypothesis, of a common pathogenesis for "CP" and "PFS", USL (or PSL) laxity. If this could be proven by "simulated operations", "CP", at least in theory, may be potentially correctible by PSL repair.

Effectiveness of external myofascial mobilisation in the management of male chronic pelvic pain of muscle spastic type: A retrospective study.

OBJECTIVE: To evaluate the outcome of men with muscle spastic chronic pelvic pain syndrome (CPPS) who underwent a comprehensive five-session fascial connectivity based external myofascial mobilisation (EMM) approach. PATIENTS AND METHODS: A retrospective chart review of patients who underwent EMM for CPPS at the Pelvic Pain Unit of Hamad Medical Corporation, Qatar between January 2019 and October 2020 was conducted. Patient's symptoms were measured with the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) scale and the numerical rating scale (NRS) before and after the completion of the sessions. The patients were given five EMM sessions as a 'once-a-week' programme. RESULTS: A total of 31 patients who completed all the EMM sessions were included. The mean (range) age of patients was 38 (20-54) years. The mean (SD) NIH-CPSI score at initial evaluation was 29.41 (8.3) and decreased to 9.14 (3.45) after the fifth visit. All the patients in the study group had a reduction of >6 points in the NIH-CPSI score, indicating a robust treatment response. The NRS reading also revealed significant improvement in pain (P < 0.001). CONCLUSIONS: : An EMM approach based on fascial connectivity led to significant symptom improvement in all the studied patients. EMM may be an effective treatment option for muscle spastic type of CPPS. Future high-quality studies with control groups are needed to confirm the present findings. Durability and long-term results are yet to be determined. ABBREVIATIONS: CP/CPPS: chronic prostatitis/chronic pelvic pain syndrome; EMM: external myofascial mobilisation; EO: external oblique; FM: fascial manipulation; GMx: gluteus maximus; HAC: hip adductor complex; HMC: Hamad Medical Corporation; IO: internal oblique; LD: latissimus dorsi; MFR: myofascial release; MM: myofascial mobilisation; NIH-CPSI: National Institute of Health-Chronic Prostatitis Symptom Index; NRS: numerical rating scale; PFPT: pelvic floor physical therapy; QoL, quality of life; TLF: thoracolumbar fascia; UPOINT: urinary (U), psychosocial (P), organ-specific (O), infection (I), neurological/systemic (N) and tenderness of pelvic floor skeletal muscles (T).

A urine-based biomarker for chronic prostatitis/chronic pelvic pain syndrome: a retrospective multi-center study.

BACKGROUND: Chronic prostatitis (CP) or chronic pelvic pain syndrome (CPPS) is one of the most common diseases in young and middle-aged men, accounting for 30% of outpatient men in urology OPD. There are no definitive diagnostic criteria for CP or CPPS and no accepted therapies that cure the disease. METHODS: We identified 372 patients with CP diagnosed from 2015 to 2018 and collect the information of age, routine urinary test, express prostatic secretion (EPS), and NIH-Chronic Prostatitis Symptom Index (NIH-CPSI). RESULTS: Our study proved a correlation between the increase of prostatic exosomal proteins (PSEPs) level and NIH-CPSI scores. Spearman's correlation coefficient showed a significant level correlation between NIH-CPSI and PSEP level (rs=0.194, P=0.0035). In the meantime, the correlation was found between the PSEP level and EPS-white blood cells. Spearman's correlation coefficient showed that there was a significant hierarchical correlation between EPS-white blood cells and PSEP level (rs=0.183, P=0.001). CONCLUSIONS: These findings highlight the potential of PSEP is a practical indicator of the symptomatic progression of CP/CPPS. Applications of PSEP assay may guide drug discovery and lead to better treatment to improve the patient's quality of life.All in all, PSEP detection in urine is safe and effective, and it is worthy of further promotion and application in clinical practice.

Analysis of bacterial community using pyrosequencing in semen from patients with chronic pelvic pain syndrome: a pilot study.

BACKGROUND: Although empirical antibacterial treatments are currently recommended for inflammatory chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), physicians cannot verify infections in most cases. Therefore, in this study, the microbiota of semen was investigated via pyrosequencing to obtain evidence underlying infectious disease. METHODS: Patients diagnosed with CP/CPPS (n=17) and healthy volunteers (n=4) participated in the study. Whole DNA was purified from the participants' semen. The DNA was amplified by polymerase chain reaction (PCR) using universal bacterial primers. All semen samples were also cultured using conventional methods. Pyrosequencing analysis of the PCR-amplified DNA was performed. RESULTS: None of the semen samples showed colony formation in conventional bacterial cultures. However, pyrosequencing revealed multiple bacterial genera in all samples, including an abundance of fastidious bacteria. Corynebacterium, Pseudomonas, Sphingomonas, Staphylococcus, and Streptococcus were frequently detected nonspecifically in both the patient and control groups. However, Achromobacter, Stenotrophomonas, and Brevibacillus were more frequently found in the CP/CPPS patients. CONCLUSIONS: The identification of various dominant species in the CP/CPPS group other than those reported in previous studies might be helpful for future etiological analysis of CP/CPPS.

Psychological factors and pain catastrophizing in men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS): a meta-analysis.

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a chronic disease with a variety of psychosocial and somatic symptoms. CP/CPPS has substantial health care costs with unclear etiology, which may be caused by psychosocial factors. Moreover, previous studies suggested that cognitive processes played a crucial role in the perception of somatic pain. Therefore, the aim of this meta-analysis was to analyze the psychosocial characteristics in men with CP/CPPS, especially the symptom of pain catastrophizing. METHODS: Relevant publications were searched in different databases including PubMed, MEDLINE, EMBASE, Google Scholar and the Cochran Library using the search terms of "Chronic prostatitis", "Chronic pelvic pain syndrome", "Psychosocial" and "Catastrophizing". The prevalence of psychological factors and pain catastrophizing in men with CP/CPPS were extracted and calculated. RESULTS: Ten studies inclusive of 1,308 patients were included. Analysis of NIH-CPSI scores showed that the severity of CP/CPPS was 23.20 (95% CI: 21.13-25.28). The severity of pain catastrophizing was 13.81 (95% CI: 9.83-17.79) estimated by coping strategies questionnaire (CSQ), while the severity of pain catastrophizing was 24.83 (95% CI: 9.19-40.47) estimated by pain catastrophizing scale (PCS). The prevalence of psychosocial symptom was 0.43 (95% CI: 0.32-0.55), while the prevalence of pain catastrophizing was 0.26 (95% CI: 0.21-0.31). CONCLUSIONS: The psychological factors and pain catastrophizing in men with CP/CPPS was serious. Furthermore, the prevalence of psychosocial symptom and pain catastrophizing was high. There might be a link between pain catastrophizing and somatic symptoms in CPPS. Thus, further prospective studies are needed to evaluate the importance of psychosocial factors in symptom severity of CP/CPPS.

Involvement of prostatic interstitial cells of Cajal in inflammatory cytokines-elicited catecholamines production: Implications for the pathophysiology of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

In a previous work using guinea pig prostate, we have identified a novel interstitial cells of Cajal (ICCs) which possess close contacts between sympathetic nerve bundles and smooth muscle cells. The ability of prostatic ICCs in mediating excitatory neural inputs was therefore studied using isolated murine prostate ICCs by collagenase digestion combined with FACS method. RT-PCR and Western blotting analyses revealed that prostatic ICCs under a quiescent state expressed abundantly the rate-limiting enzymes essential for catecholamine synthesis. Moreover, distinct proinflammatory cytokines (e.g. IL-1ß, IL-8, ICAM-1 and TNF-α) could significantly stimulate the expression levels of the rate-limiting enzymes of catecholamine production in prostate ICCs. Mechanistically, the above-mentioned stimulatory effects of proinflammatory cytokines appeared to be mediated via activation of NF-κB, HIF-1α and HDACs signaling pathways. Considering that prostatic catecholamine overactivity serves as an essential etiology of pelvic pain by indirectly stimulating the smooth muscle cell proliferation, or by directly causing muscular spasm, our results collectively suggest that targeting the NF-κB, HIF-1α and HDACs pathways in prostate ICCs be considered as a new strategy for treatment of chronic pelvic pain syndrome (CPPS) induced by chronic prostatitis (CP). Overall, the current study should shed novel light on the biology of this unique prostate ICCs.

Utility of trigger point injection as an adjunct to physical therapy in men with chronic prostatitis/chronic pelvic pain syndrome.

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is often associated with pelvic floor muscle spasm. While pelvic floor physical therapy (PFPT) is effective, some men are unable to resolve their symptoms and have residual trigger points (TPs). TP injection has been used for treatment in several neuromuscular pain syndromes. The objective of this study was to examine the efficacy and side effects of TP injection in men with CP/CPPS and pelvic floor spasm refractory to PT. METHODS: Using an IRB approved Men's Health Registry we reviewed the records of all men with a diagnosis of CP/CPPS who received at least 1 TP injection. Patients were phenotyped with UPOINT (all had the "T" domain for tenderness of muscle) and symptoms measured with the NIH Chronic Prostatitis Symptom Index (CPSI). Response was measured by a 5-point Global Response Assessment (GRA) and change in CPSI (paired t-test). For pelvic TPs, a pudendal block was done in lithotomy position and then each TP was identified transrectally by palpation. A nerve block needle was passed through the perineum into the TP confirmed by palpation. Between 0.5-1 cc was injected into each TP of a local anesthetic mixture (30:70 of 2% lidocaine and 0.25% bupivacaine). For anterior TPs, an ultrasound guided ilioinguinal block was done first and then each TP injected by direct palpation through the abdominal skin. Men were offered up to three sets of injections separated by 6 weeks each. RESULTS: We identified 37 patients who had a total of 68 procedures. Three men had no follow-up after their first injection and were included for side effects but not included for outcome. The indication was failure to progress on PT in 33, recurrent symptoms in 1 and refusal to do PT in 3. Mean age was 43.7 years (range 21-70 years) and median UPOINT domains was 3 (range 1-5). Initial CPSI was pain 13.7±3.4, urinary 5.3±2.2, quality of life 9.8±2.1 and total 28.8±6.0. 16 men had 1 injection, 11 had 2 and 10 had 3. All had pelvic TPs injected and 9 also had anterior TPs. By GRA, 12 had significant improvement (35.3%), 10 had some improvement (29.4%), 11 had no change (32.3%) and 1 was worse (2.9%). Mean CPSI dropped from 28.8±6.0 to 21.8±7.2 (P<0.0001). 18 men had a drop of 6 or more points in CPSI (53%). Of note, none of 3 men who were noncompliant with PT had benefit. 3 men had temporary numbness in the lateral thigh after the injection (4.4%) and 1 had difficulty weight bearing on 1 leg for about 30 minutes. CONCLUSIONS: TP injection in CP/CPPS patients as an adjunct to PT is well tolerated and leads to symptom improvement in about half. Durability and long term results are yet to be determined.