Experimental autoimmune prostatitis induces chronic pelvic pain

Pain is the hallmark of patients with chronic prostatitis (CP) and chronic pelvic pain syndrome (CPPS). Despite numerous hypotheses, the etiology and pathogenesis remain unknown. To better understand CP/CPPS, we used a murine experimental autoimmune prostatitis model to examine the development, localization, and modulation of pelvic pain. Pelvic pain was detected 5 days after antigen instillation and was sustained beyond 30 days, indicating the development of chronic pain. The pain was attenuated by lidocaine treatment into the prostate, but not into the bladder or the colon, suggesting that pain originated from the prostate. Experimental autoimmune prostatitis histopathology was confined to the prostate with focal periglandular inflammatory infiltrates in the ventral, dorsolateral, and anterior lobes of the mouse prostate. Inflammation and pelvic pain were positively correlated and increased with time. Morphologically, the dorsolateral prostate alone showed significantly increased neuronal fiber distribution, as evidenced by increased protein gene product 9.5 expression. Pelvic pain was attenuated by treatment with the neuromodulator gabapentin, suggesting spinal and/or supraspinal contribution to chronic pain. These results provide the basis for identifying mechanisms that regulate pelvic pain and the testing of therapeutic agents that block pain development in CP/CPPS.     

Management of men diagnosed with chronic prostatitis/chronic pelvic pain syndrome who have failed traditional management

For many patients, the traditional biomedical model that physicians have used to manage chronic prostatitis does not work. This article describes innovative treatment strategies for chronic prostatitis/chronic pelvic pain syndrome, with an emphasis on novel biomedical physical therapy and biopsychosocial approaches to the management of individualized patient symptoms.     

Acupuncture for chronic prostatitis/chronic pelvic pain syndrome: study protocol for a randomized controlled trial

Background

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common condition affecting men of all ages. Acupuncture may be an effective treatment option for CP/CPPS, but evidence is limited. We propose to evaluate the effectiveness of acupuncture in a rigorously conducted trial.

Methods

Ten hospitals will recruit 440 participants with CP/CPPS in China from October 2017 to December 2019. Participants will be randomly allocated to acupuncture or sham acupuncture with a 1:1 ratio using computerized simple random sampling. The whole study consists of 2-week baseline, 8-week treatment, and 24-week follow up. Twenty 30-mintute sessions of acupuncture or sham acupuncture treatment will be provided between week 1 and 8. The two co-primary outcomes are the proportion of responders at week 8 and week 32. Secondary outcomes include proportion of responders in the two groups at different time points; change in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) total score; change in the NIH-CPSI subscales; change in the International Prostate Symptom Score; change in the Hospital Anxiety and Depression Scale; expectation assessments; proportions of participants in each response category of the Global Response Assessment; change in the International Index of Erectile Function 5; change in the five-level EuroQol five-dimensional questionnaire and a visual analogue scale; and changes in peak and average urinary flow rate.

Discussion

This study will provide robust evidence on whether acupuncture is effective for relieving symptoms of CP/CPPS.

Trials registration

ClinicalTrials.gov, NCT03213938. Registered on 5 July 2017.

     

Peritoneal fluid eicosanoids in chronic pelvic pain

Products of the cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism were estimated in the cul-de-sac fluid from patients with endometriosis, pelvic adhesions and normal laparoscopic examinations, with and without chronic pelvic pain. No correlation between the symptoms, underlying diagnoses, and the concentrations of eicosanoids were observed.     

Single‐cell multi‐omics analysis presents the landscape of peripheral blood T‐cell subsets in human chronic prostatitis/chronic pelvic pain syndrome

Cumulative evidence suggests that abnormal differentiation of T lymphocytes influences the pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Thus, understanding the immune activation landscape of CP/CPPS would be helpful for improving therapeutic strategies. Here, we utilized BD™ AbSeq to digitally quantify both the protein and mRNA expression levels in single peripheral blood T cells from two CP/CPPS patients and two healthy controls. We utilized an integrated strategy based on canonical correlation analysis of 10 000+ AbSeq profiles and identified fifteen unique T‐cell subpopulations. Notably, we found that the proportion of cluster 0 in the CP/CPPS group (30.35%) was significantly increased compared with the proportion in the healthy control group (9.38%); cluster 0 was defined as effector T cells based on differentially expressed genes/proteins. Flow cytometry assays confirmed that the proportions of effector T‐cell subpopulations, particularly central memory T cells, T helper (Th)1, Th17 and Th22 cells, in the peripheral blood mononuclear cell populations of patients with CP/CPPS were significantly increased compared with those of healthy controls (P < 0.05), further confirming that aberration of effector T cells possibly leads to or intensifies CP/CPPS. Our results provide novel insights into the underlying mechanisms of CP/CPPS, which will be beneficial for its treatment.     

High frequency of chronic bacterial and non-inflammatory prostatitis in infertile patients with prostatitis syndrome plus irritable bowel syndrome

Background

Although prostatitis syndrome (PS) and irritable bowel syndrome (IBS) are common disorders, information on the prevalence of IBS in infertile patients with PS is relatively scanty. Therefore, this study was undertaken to estimate the frequency of PS and IBS and to evaluate the prevalence of the various diagnostic categories of prostatitis.

Methodology/Principal Findings

This study enrolled 152 patients with PS, diagnosed by the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) in an andrological setting, and 204 patients with IBS, diagnosed according to the Rome III diagnostic criteria in a gastroenterological setting. The patients with PS were asked to fulfill the Rome III questionnaire for IBS, whereas patients with IBS were asked to complete the NIH-CPSI. The simultaneous presence of PS and IBS was observed in 30.2% and 31.8% of the patients screened by andrologists and gastroenterologists, respectively. Altogether, 111 patients had PS plus IBS (31.2%). They had a total NIH-CPSI and pain subscale scores significantly higher than patients with PS alone. Gastrointestinal symptoms in patients with PS plus IBS were similar to those reported by patients with IBS alone and significantly greater in patients with PS alone. Patients with PS plus IBS had a significantly higher frequency of chronic bacterial prostatitis (category II) and lower of non-inflammatory prostatitis (category IIIB), compared to patients with PS alone. The frequency of inflammatory prostatitis (category IIIA) resulted similar.

Conclusions/Significance

Prostatitis syndromes and IBS are frequently associated in patients with PS- or IBS-related symptoms. These patients have an increased prevalence of chronic bacterial and non-inflammatory prostatitis.     

完全弗氏佐剂诱导大鼠慢性骨盆疼痛综合征炎性痛模型的制备*

目的: 建立大鼠慢性骨盆疼痛综合征(CPPS)炎性痛模型并进行评价,为CPPS炎症引起的慢性骨盆疼痛的外周及中枢机制研究提供可靠的动物模型。方法: 将60只SD雄性大鼠随机分成空白组,假手术组和模型组,每组20只。采用向大鼠前列腺腹侧叶注射完全弗氏佐剂(CFA)的方法制备CPPS炎性痛模型。术后观察大鼠一般情况变化;分别于造模后7 d,14 d,21 d,28 d,35 d测定大鼠足底和阴囊热刺激疼痛阈值;取材后前列腺组织称重计算前列腺指数;显微镜下观察大鼠前列腺组织病理变化并用半定量法评价前列腺组织损伤程度,以评价模型是否成功。结果: 模型成功17只,成模率为85%。与空白组和假手术组比较,造模后大鼠的活动度、毛发光泽度降低,排尿量增加。足底和阴囊热刺激疼痛阈值显著降低并可稳定维持1个月以上(P＜0.01)。前列腺湿重和前列腺指数均显著性提高(P＜0.01)。前列腺组织肉眼可见明显水肿,与周围组织粘连严重;镜下可见腺腔萎缩,间质内大量炎性细胞浸润。结论: 利用向大鼠前列腺腹侧叶注射CFA的方法,可成功复制CPPS炎性痛模型,这将为后续CPPS发病机制的研究,特别是疼痛行为与潜在炎症和神经损伤之间的机制联系提供有价值的工具。     

CCL2 and CCL3 are essential mediators of pelvic pain in experimental autoimmune prostatitis

Experimental autoimmune prostatitis (EAP) is a murine model of chronic prostatitis/chronic pelvic pain syndrome (CPPS) in men, a syndrome characterized by chronic pelvic pain. We have demonstrated that chemokine ligands CCL2 and CCL3 are biomarkers that correlate with pelvic pain symptoms. We postulated that CCL2 and CCL3 play a functional role in CPPS and therefore examined their expression in EAP. Upon examination of the prostate 5 days after induction of EAP, CCL2 mRNA was elevated 2- to 3-fold, CCL8 by 15-fold, CCL12 by 12- to 13-fold, and CXCL9 by 2- to 4-fold compared with control mice. At 10 days the major chemokines were CXCL13 and CXCL2; at 20 days CCL2 (1- to 2-fold), CCL3 (2- to 3-fold) and CCL11 (2- to 3-fold); and at 30 days, CCL12 (20- to 35-fold) and smaller increases in CCL2, CCL3, and XCL1. Chemokine elevations were accompanied by increases in mast cells and B cells at 5 days, monocytes and neutrophils at day 10, CD4+ T cells at day 20, and CD4+ and CD8+ T cells at day 30. Anti-CCL2 and anti-CCL3 neutralizing antibodies administered at EAP onset attenuated pelvic pain development, but only anti-CCL2 antibodies were effective therapeutically. CCL2- and its cognate receptor CCR2-deficient mice were completely protected from development of pain symptoms but assumed susceptibility after reconstitution with wild-type bone marrow. CCL3-deficient mice showed resistance to the maintenance of pelvic pain while CCR5-deficient mice did not show any lessening of pelvic pain severity. These results suggest that the CCL2-CCR2 axis and CCL3 are important mediators of chronic pelvic pain in EAP.     

慢性前列腺炎患者治疗过程心理干预的意义

目的:探讨慢性前列腺炎患者的的心理状态及心理治疗的意义.方法:采用汉密尔顿焦虑量表(HAMA)评定243例慢性前列腺炎患者,80例其他疾病患者,80例健康人的心理状况.并将慢性前列腺炎患者随机分为两组:对照组123例,应用药物治疗;治疗组120例,除药物治疗外,辅助心理治疗.治疗前后采用汉密尔顿焦虑量表(HAMA)评定心理状况,临床症状IPSS评分评定疗效.结果:慢性前列腺炎患者HAMD分值明显高于健康人,也高于其他疾病患者,治疗组的治愈率和有效率均明显优于对照组,复发率低于对照组.结论:对于慢性前列腺炎患者,应用心理治疗是必要的和有效的1.     

Analysis of cytokines in seminal plasma and blood sera of patients with chronic prostatitis during immunotherapy with natural complex of cytokines and antimicrobial peptides

Levels of pro- and anti-inflammatory cytokines (TNFalpha, IL-6, IL-8, IL-10) were studied in blood sera and seminal plasma of healthy volunteers and patients with chronic bacterial prostatitis (CBP) or chronic abacterial prostatitis (CABP). Assessment of effect of immunotropic drug Superlymph with direct antimicrobial action for treatment of mentioned groups of patients was performed. It was shown that seminal plasma of patients with CBP and CABP contained higher levels of IL-6 compared with healthy subjects. IL-8 level was increased in small part of patients with CBP and CABP. Changes in cytokine status of patients with CBP and CABP that occurred during treatment and manifested in decrease of proinflammatory cytokines levels (IL-6 and IL-8) and increase of antiinflammatory cytokine level (IL-10) point to reduction of inflammatory process in prostate. Clinical effect of complex treatment in patients with CBP considering eradication of pathogen and shortening of duration of antibacterial treatment amounted 95%. Monotherapy of patients with CABP with Superlymph was effective in 72%.     

Immunoreactive vasopressin in bull seminal fluid

Immunoreactive arginine vasopressin (irAVP) was measured in seminal fluid with and without extraction using a specific radioimmunoassay (RIA). A large fraction of irAVP was removed after extraction on octadecasilylsilica cartridges. The measured amount of irAVP corresponded to the levels found in blood plasma. Dilutions of seminal plasma extracts were parallel with the RIA standard curve. On reversed phase HPLC the extracted material coeluted with synthetic AVP. These findings suggest an identity of this immunoreactive material with intact AVP. During incubations of synthetic AVP and its analogue 8-D-arginine vasopressing (8-DAVP) in seminal plasma, immunoreactivity decreased considerably with the former peptide, while the concentration of 8-DAVP was not significantly altered.     

细菌性前列腺炎患者前列腺液菌群调查及耐药谱分析

目的了解细菌性前列腺炎患者菌群分布及其耐药现状,更有效地对细菌性前列腺炎进行预防控制。方法对我院2005年10月至2007年9月拟诊为细菌性前列腺炎的患者266例,取前列腺液做细菌需氧及5%CO2环境培养,以Phoenix 100型全自动细菌分析系统进行菌种鉴定及药物敏感试验,综合分析结果。结果266例患者中前列腺液培养阳性者204例,阳性率为76.69%。其中葡萄球菌152株,占检出菌株数的74.51%。检出主要细菌为：溶血葡萄球菌82株（40.2%）,表皮葡萄球菌34株（16.67%）,粪肠球菌25株（12.25%）,头状葡萄球菌10株（4.9%）,金黄色葡萄球菌5株（2.45%）。葡萄球菌对氨苄西林、青霉素耐药率达到100%,对万古霉素、呋喃妥因、吗啉噁酮敏感率分别为100%、95.9%、95.1%。结论细菌性前列腺炎患者多由条件致病菌感染所致,尤其以凝固酶阴性葡萄球菌感染多见,患者年龄呈逐渐年轻化趋势;万古霉素、呋喃妥因、吗啉噁酮对葡萄球菌高度敏感。