Immune mediators of chronic pelvic pain syndrome

Murphy, SB; Schaeffer, Anthony J.; Thumbikat, Praveen

doi:10.1038/nrurol.2014.63

Cited by 90 publications

(93 citation statements)

References 142 publications

(168 reference statements)

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“…In order to analyze, whether the detected impairment of standard semen parameters is in fact associated with CP/CPPS and not with elder age of the patient cohort, we performed age-matched comparative analyses. We considered only young CP/CPPS type IIIb patients (n = 32, median age 27 (range [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32]) and compared those to healthy controls. We still detected a significant association between CP/CPPS and reduced sperm motility (total and progressive, p < 0.001), increased aberrations in sperm morphology (head and tail defects, p < 0.001) and reduced seminal pH (p < 0.001).…”

Section: Resultsmentioning

confidence: 99%

Chronic Prostatitis Affects Male Reproductive Health and Is Associated with Systemic and Local Epigenetic Inactivation of C-X-C Motif Chemokine 12 Receptor C-X-C Chemokine Receptor Type 4

Schagdarsurengin¹,

Teuchert²,

Hagenkötter³

et al. 2016

Urol Int

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Background/Aims/Objectives: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has detrimental effects on the quality of life including the aspect of sexual dysfunction. The aim of the study was to identify if there was an adverse effect on the male genital compartment and if there are systemic or compartment-specific local signals for epigenetic dysregulation of inflammatory factors in CP/CPPS patients. Methods: One hundred five NIH IIIb CP/CPPS patients and 41 healthy men were recruited and underwent investigations of urines, semen and blood. Promoter methylation and expression of the chemokine C-X-C motif chemokine 12 and its receptor C-X-C chemokine receptor type 4 (CXCR4) (involved in the recruitment of mast cells) were analyzed in prostate epithelial cell lines and in healthy volunteers' and patients' blood, ejaculate cell pellets, and separated ejaculate fractions (sperm and seminal somatic cells). Results: Independently from age, CP/CPPS NIH IIIb was associated with significant impairment of sperm motility, morphology and semen pH (p < 0.001). Patients older than 33 years showed significantly increased seminal interleukin-8 and serum prostate specific antigen values. In patients, the CXCR4 mRNA-expression was significantly decreased in whole blood and ejaculate cell pellets due to promoter hypermethylation. Analyses on separated fractions of sperm and seminal somatic cells revealed that sperm DNA was unaffected, whereas somatic cell DNA was differentially methylated. Conclusions: NIH IIIb CP/CPPS has negative effects on surrogate parameters of male fertility and is associated significantly with systemic and local epigenetic inactivation of CXCR4.

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Section: Resultsmentioning

confidence: 99%

Chronic Prostatitis Affects Male Reproductive Health and Is Associated with Systemic and Local Epigenetic Inactivation of C-X-C Motif Chemokine 12 Receptor C-X-C Chemokine Receptor Type 4

Schagdarsurengin¹,

Teuchert²,

Hagenkötter³

et al. 2016

Urol Int

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“…Patients with CP/CPPS report pain in the perineum, rectum, prostate, penis, testicles, and/or abdomen 28 , experience a higher degree of psychological stress than control patients 29 , and commonly present with symptoms of or are diagnosed with comorbid chronic pelvic pain or mood disorders 5,[29][30][31] . Recurrent infection, leaky epithelium, neurogenic inflammation, and autoimmunity have all been surmised as potential underlying causes of CP/CPPS 2,32,33 , as well as mast cell activation and degranulation 34 . Expressed prostatic secretions from men with CP/ CPPS had increased mast cell tryptase and nerve growth factor (NGF) levels .…”

Section: Introductionmentioning

confidence: 99%

Assessment of Perigenital Sensitivity and Prostatic Mast Cell Activation in a Mouse Model of Neonatal Maternal Separation

Fuentes

Pierce

O’Neil

et al. 2015

JoVE

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Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has a lifetime prevalence of 14% and is the most common urological diagnosis for men under the age of 50, yet it is the least understood and studied chronic pelvic pain disorder. A significant subset of patients with chronic pelvic pain report having experienced early life stress or abuse, which can markedly affect the functioning and regulation of the hypothalamicpituitary-adrenal (HPA) axis. Mast cell activation, which has been shown to be increased in both urine and expressed prostatic secretions of CP/ CPPS patients, is partially regulated by downstream activation of the HPA axis. Neonatal maternal separation (NMS) has been used for over two decades to study the outcomes of early life stress in rodent models, including changes in the HPA axis and visceral sensitivity. Here we provide a detailed protocol for using NMS as a preclinical model of CP/CPPS in male C57BL/6 mice. We describe the methodology for performing NMS, assessing perigenital mechanical allodynia, and histological evidence of mast cell activation. We also provide evidence that early psychological stress can have long-lasting effects on the male urogenital system in mice. Video LinkThe video component of this article can be found at

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“…Mechanism in the development of neuropathic pain was interpreted in Fig. 2 [62]. Numerous lines of evidence and ongoing investigations underline the role of the adaptive immune response and activation of autoimmunity in the development of CP/CPPS (Fig.…”

Section: Proposed Mechanisms In Development Of Pain In Cp/cppsmentioning

confidence: 99%

“…Prostate antigens generated from damage to the epithelium in the presence of an activated CD4 T-cell response, with unchecked mast cell degranulation and increased numbers of CD8 T-cells can result in the development of autoimmunity, which further exacerbates these mechanisms (13). Reproduced from the article of Murphy et al Nat Rev Urol 2014;11:259-69 [62] with permission. TGF: transforming growth factor beta, ERK: extracellular signal-regulated kinases, JNK: c-Jun N-terminal kinase, NFB: nuclear factor kappa B.…”

Section: In-chang Cho and Seung Ki Min Etiologies Of Cp/cpps 97mentioning

confidence: 99%

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Proposed New Pathophysiology of Chronic Prostatitis/Chronic Pelvic Pain Syndrome

Cho

Min

2015

Urogenit Tract Infect

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The most common type of prostatitis is category III, also known as chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). The current National Institutes of Health definition of CP/CPPS includes genitourinary pain with or without voiding symptoms in the absence of uropathogenic bacteria, as detected by standard microbiological methods, or other identifiable causes such as malignancy. Many different etiologies and mechanisms of pathogenesis of CP/CPPS have been proposed with a suggested role for immunological, neurological, endocrine, and psychological factors. We examined the data supporting the role of each of these areas and also examined the possible interrelationship of these factors in producing the symptoms of CP/CPPS. Prostatitis types IIIa and IIIb are classified according to the presence of pain without concurrent presence of bacteria; however, it is becoming more evident that, although levels of bacteria are not directly associated with levels of pain, the presence of bacteria might act as the initiating factor that drives primary activation of mast-cell-mediated inflammation in the prostate. The gate control theory provides a neurologic basis for the influence of both somatic and psychological factors on pain. Acceptance of chronic pain as a diagnosis may be difficult for the clinician and patient, however it is an important concept in the care of CP/CPPS, which enables the use of pain-directed therapies. Management of CP/CPPS will remain challenging; however, this review provides a better understanding of the condition and improved management strategies based on the newest evidence and concepts available. Keywords: Prostatitis; Chronic pain; Physiopathology INTRODUCTIONChronic prostatitis/chronic pelvic pain syndrome (CP/ CPPS) is a condition of chronic pelvic pain in men [1]. It has been estimated that between 2% and 14% of men worldwide may have symptoms of CP/CPPS [2,3]. The diagnosis is made on the basis of symptoms of pain with or without voiding symptoms in the absence of other identifiable causes [4]. The etiology of symptoms in a given patient can be from many causes. Whether there are identifiable, repeatable patterns of causes of symptoms, or just individual patients with distinct individual phenotypes are unknown. Because CP/CPPS is a common condition associated with significant physical, mental, and social burden, the medical community has made tremendous efforts to understand the condition and improve management strategies. Despite these efforts, answers remain elusive. Robust tools to measure symptom severity Our improved understanding of the etiology and clinical phenotypes associated with CP/CPPS has made the condition less of a clinical enigma. Acceptance of clinical definitions (and classification system) and validated, reliable outcome questionnaire (the CP symptom index) has led to high-quality treatment evidenced from randomized placebo-controlled trials. This article is a very timely review of the topic and provides the clinician with an improved understanding of CP/CPPS a...

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Immune mediators of chronic pelvic pain syndrome

Cited by 90 publications

References 142 publications

Chronic Prostatitis Affects Male Reproductive Health and Is Associated with Systemic and Local Epigenetic Inactivation of C-X-C Motif Chemokine 12 Receptor C-X-C Chemokine Receptor Type 4

Chronic Prostatitis Affects Male Reproductive Health and Is Associated with Systemic and Local Epigenetic Inactivation of C-X-C Motif Chemokine 12 Receptor C-X-C Chemokine Receptor Type 4

Assessment of Perigenital Sensitivity and Prostatic Mast Cell Activation in a Mouse Model of Neonatal Maternal Separation

Proposed New Pathophysiology of Chronic Prostatitis/Chronic Pelvic Pain Syndrome

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