MECHANISMS IN PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME

No AccessJournal of UrologyReview Articles1 Sep 2004MECHANISMS IN PROSTATITIS/CHRONIC PELVIC PAIN SYNDROMEis companion ofMechanisms in Prostatitis/Chronic Pelvic Pain Syndrome MICHEL A. PONTARI and MICHAEL R. RUGGIERI MICHEL A. PONTARIMICHEL A. PONTARI and MICHAEL R. RUGGIERIMICHAEL R. RUGGIERI View All Author Informationhttps://doi.org/10.1097/01.ju.0000136002.76898.04AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We reviewed the current literature on mechanisms involved in the pathogenesis of prostatitis/chronic pelvic pain syndrome (CPPS). Materials and Methods: A literature review for the years 1966 to 2003 was performed using the MEDLINE database of the United States National Library of Medicine. Results: National Institutes of Health categories I and II prostatitis result from identifiable prostatic infections, whereas patients with category IV are asymptomatic. The majority of symptomatic cases are category III or chronic prostatitis (CP)/CPPS. The etiology of CP/CPPS is unknown. The traditional marker of inflammation, namely white blood cells in prostatic fluids, does not correlate with the predominant symptom of pelvic pain. An imbalance toward increased proinflammatory and decreased anti-inflammatory cytokines has been implicated and a few studies have shown some correlation of this with pelvic pain. The imbalance in some men may result from polymorphisms at the cytokine loci. An autoimmune process may be involved and experimental evidence indicates that this can be under hormonal influence. Recent findings include possible defects in the androgen receptor. The prostate may not even be the source of the symptoms. Pelvic pain also correlates with the neurotrophin nerve growth factor implicated in neurogenic inflammation and central sensitization. Finally, psychological stress may produce measurable biochemical changes and influence the other processes. The role of normal prostatic bacterial flora in inciting the inflammatory response has also been reconsidered. Conclusions: The symptoms of CP/CPPS appear to result from an interplay between psychological factors and dysfunction in the immune, neurological and endocrine systems. References 1 : NIH consensus definition and classification of prostatitis. JAMA1999; 282: 236. Crossref, Medline, Google Scholar 2 : Classification of benign diseases associated with prostatic pain: prostatitis or prostatodynia? (letter to the editor). J Urol1978; 120: 266. Link, Google Scholar 3 : Diagnosis and treatment of 409 patients with prostatitis syndromes. Urology1993; 41: 301. Crossref, Medline, Google Scholar 4 : Research guidelines for chronic prostatitis: consensus report from the first National Institutes of Health International Prostatitis Collaborative Network. Urology1999; 54: 229. Crossref, Medline, Google Scholar 5 : Chronic prostatitis: a thorough search for etiologically involved microorganisms in 1,461 patients. Infection1991; 19: S119. Crossref, Medline, Google Scholar 6 : Bacteria in the chronic prostatitischronic pelvic pain syndrome: molecular approaches to critical research questions. J Urol2002; 167: 2574. Link, Google Scholar 7 : Prevalence and significance of prostatic inflammation. J Urol1981; 125: 215. Link, Google Scholar 8 : Leukocytes and bacteria in men with chronic prostatitis/chronic pelvic pain syndrome compared to asymptomatic controls. J Urol2003; 170: 818. Link, Google Scholar 9 : Leukocyte and bacterial counts do not correlate with severity of symptoms in men with chronic prostatitis: the National Institutes of Health Chronic Prostatitis Cohort Study. J Urol2002; 168: 1048. Link, Google Scholar 10 : Elevated levels of proinflammatory cytokines in the semen of patients with chronic prostatitis/chronic pelvic pain syndrome. Urology1998; 52: 744. Crossref, Medline, Google Scholar 11 : Seminal plasma cytokine levels in the diagnosis of chronic pelvic pain syndrome. Int J Urol2001; 8: 495. Google Scholar 12 : Biochemical markers for inflammation and glands that contribute to the semen in chronic prostatitis patients. J Urol2000; 163: 26. abstract 112. Google Scholar 13 : Antiviral effects of recombinant tumour necrosis factor in vitro. Nature1986; 323: 816. Google Scholar 14 : Noninflammatory chronic pelvic pain syndrome: immunological study in blood, ejaculate and prostate tissue. Eur Urol2001; 39: 72. Google Scholar 15 : IL-1β and TNF-α in prostatic secretions are indicators in the evaluation of men with chronic prostatitis. J Urol2000; 164: 214. Link, Google Scholar 16 : Recent advances in the understanding of interleukin-2 signal transduction. J Clin Immunol1998; 18: 307. Google Scholar 17 : Interleukin-10 levels in seminal plasma: implications for chronic prostatitis-chronic pelvic pain syndrome. J Urol2002; 167: 753. Link, Google Scholar 18 : Evaluation of the cytokines interleukin 8 and epithelial neutrophil activating peptide 78 as indicators of inflammation in prostatic secretions. Urology2000; 56: 1025. Crossref, Medline, Google Scholar 19 : Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. J Clin Invest1989; 84: 1045. Google Scholar 20 : Involvement of the proinflammatory cytokines tumor necrosis factor-alpha, IL-1 beta, and IL-6 but not IL-8 in the development of heat hyperalgesia: effects on heat-evoked calcitonin gene-related peptide release from rat skin. J Neurosci2000; 20: 6289. Google Scholar 21 : Diagnostic value of serial cytokine changes in expressed prostatic secretions. J Urol2000; 163: 24. abstract 105. Google Scholar 22 : Effect of ciprofloxacin on the activation of the transcription factors nuclear factor kappaB, activator protein-1 and nuclear factor-interleukin-6, and interleukin-6 and interleukin-8 mRNA expression in a human endothelial cell line. Clin Sci2000; 99: 405. Google Scholar 23 : IL-1ra versus IL-1 levels in prostatic fluid from prostatitis patients. Urol Int1998; 60: 92. Crossref, Medline, Google Scholar 24 : Interleukin-10: biology, role in inflammation and autoimmunity. Ann Allergy Asthma Immunol1997; 79: 469. Crossref, Medline, Google Scholar 25 : The −308 tumor necrosis factor-alpha promoter polymorphism effects transcription. Mol Immunol1997; 34: 391. Google Scholar 26 : An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet1997; 24: 1. Google Scholar 27 : Cytokine polymorphisms in men with chronic prostatitis/chronic pelvic pain syndrome: association with diagnosis and treatment response. J Urol2002; 168: 331. Link, Google Scholar 28 : Predominant role of tumor necrosis factor-alpha in human monocyte IL-10 synthesis. J Immunol1993; 151: 6853. Google Scholar 29 : Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med1989; 170: 2081. Crossref, Medline, Google Scholar 30 : Resolution of the chronic pelvic pain syndrome after renal transplantation. J Urol2000; 164: 127. Link, Google Scholar 31 : Favorable role of interleukin 10 in patients with polymyalgia rheumatica. J Rheumatol1999; 26: 1318. Medline, Google Scholar 32 : Interleukin 10 is a potent growth and differentiation factor for activated human B lymphocytes. Proc Natl Acad Sci USA1992; 89: 1890. Google Scholar 33 : Experimental autoimmune damage to rat male accessory glands. II. T cell requirement in adoptive transfer of specific tissue damage. Am J Reprod Immunol1984; 5: 15. Google Scholar 34 : Inflammatory cells and MHC class II antigens expression in prostate during time-course experimental autoimmune prostatitis development. Clin Immunol Immunopathol1997; 85: 158. Google Scholar 35 : Activation of cytotoxic cells by syngeneic prostate antigens in experimental autoimmune vesiculo-prostatitis. Autoimmunity1991; 9: 151. Google Scholar 36 : Development of a mouse model for nonbacterial prostatitis. J Urol1994; 152: 247. Link, Google Scholar 37 : Oxidative stress in prostatic fluid of patients with chronic pelvic pain syndrome: correlation with gram positive bacterial growth and treatment response. J Androl2000; 21: 669. Google Scholar 38 : Autoimmune prostatitis: evidence of T cell reactivity with normal prostatic proteins. Urology1997; 50: 893. Google Scholar 39 : PSA is a candidate self-antigen in autoimmune chronic prostatitis/chronic pelvic pain syndrome. Prostate2000; 44: 49. Google Scholar 40 : Autoimmune T cell responses to seminal plasma in chronic pelvic pain syndrome (CPPS). Clin Exp Immunol2002; 128: 302. Google Scholar 41 : Intraprostatic spermatozoa. Hum Pathol1988; 19: 541. Google Scholar 42 : The role of Chlamydia trachomatis in chronic abacterial prostatitis: a study using ultrasound guided biopsy. J Urol1989; 141: 332. Link, Google Scholar 43 : Intraprostatic antibody deposition in chronic abacterial prostatitis. Br J Urol1990; 65: 598. Google Scholar 44 : Prostate histopathology and the chronic prostatitis/chronic pelvic pain syndrome: a prospective biopsy study. J Urol1999; 162: 2014. Link, Google Scholar 45 : The role of androgens and estrogens in the pathogenesis of experimental nonbacterial prostatitis. J Urol1988; 140: 1049. Link, Google Scholar 46 : Expression of proinflammatory genes during estrogen-induced inflammation of the rat prostate. Prostate2000; 44: 19. Google Scholar 47 : Experimental autoimmune prostatitis: in vivo induction of the autoimmune response to lymphocytic soluble factors. Alterations at the endocrine metabolism level. Am J Reprod Immunol1998; 39: 226. Google Scholar 48 : Effect of male accessory glands autoaggression on androgenic cytosolic and nuclear receptors of rat prostate. Cell Mol Biol1992; 38: 201. Google Scholar 49 : A randomized placebo-controlled multicentre study to evaluate the safety and efficacy of finasteride for male chronic pelvic pain syndrome (category IIIA chronic nonbacterial prostatitis). BJU Int2004; 93: 991. Google Scholar 50 : X Chromosomal short tandem repeat polymorphisms near the phosphoglycerate kinase gene in men with chronic prostatitis. Biochim Biophys Acta2002; 1586: 99. Google Scholar 51 : Diverse eukaryotic transcripts suggest short tandem repeats have cellular functions. Biochem Biophys Res Comm2002; 298: 581. Google Scholar 52 : Adrenocorticotropin and beta-endorphin release from rat adenohypophysis in vitro: inhibition by prostaglandin E2 formed locally in response to vasopressin and corticotropin-releasing factor. Endocrinology1984; 115: 895. Google Scholar 53 : Correlation of β-endorphin and PGE2 levels in prostatic fluid of chronic prostatitis patients with diagnosis and treatment response. J Urol2001; 166: 1738. Link, Google Scholar 54 : Similarity of distributions of spinal c-fos and plasma extravasation after acute chemical irritation of the bladder and the prostate. J Urol2000; 164: 1751. Link, Google Scholar 55 : Cell relationship in a Wistar rat model of spontaneous prostatitis. J Urol2001; 166: 323. Link, Google Scholar 56 : Nerve growth factor: a neurokine orchestrating neuroimmune-endocrine functions. Mol Neurobiol2001; 24: 183. Google Scholar 57 : Nerve growth factor and chronic prostatitis/chronic pelvic pain syndrome. Urology2002; 59: 603. Google Scholar 58 : Nerve growth factor (NGF) regulates adult rat cultured dorsal root ganglion neuron responses to the excitotoxin capsaicin. Neuron1988; 1: 973. Google Scholar 59 : Nerve growth factor induces mast cell degranulation without changing intracellular calcium levels. FEBS Lett1986; 198: 315. Google Scholar 60 : Nerve growth factor regulates expression of neuropeptide genes in adult sensory neurons. Nature1989; 337: 362. Google Scholar 61 : Isolated hepatic granulomas from mice infected with Schistosoma mansoni contain nerve growth factor. Infect Immun1991; 59: 4443. Google Scholar 62 : The induction and maintenance of central sensitization is dependent on N-methyl-D-aspartic acid receptor activation; implications for the treatment of post-injury pain hypersensitivity states. Pain1991; 44: 293. Google Scholar 63 : Differential regulation of trkA and p75 in noradrenergic pelvic autonomic ganglion cells after deafferentation of their cholinergic neighbours. Eur J Neurosci2001; 13: 211. Google Scholar 64 : Testosterone and nerve growth factor have distinct but interacting effects on structure and neurotransmitter expression of adult pelvic ganglion cells in vitro. Neuroscience2001; 108: 331. Google Scholar 65 : Cooperative regulation of nerve growth factor synthesis and secretion in fibroblasts and astrocytes by fibroblast growth factor and other cytokines. Brain Res1992; 569: 14. Google Scholar 66 : Peptides and neurogenic inflammation. Br Med Bull1987; 43: 386. Google Scholar 67 : The role of Th2 cytokines in mast cell homeostasis. Immunol Rev2001; 179: 82. Google Scholar 68 : Fears, sexual disturbances and personality features in men with prostatitis: a population-based cross-sectional study in Finland. BJU Int2001; 88: 35. Google Scholar 69 : A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Med Care1996; 34: 220. Google Scholar 70 : Quality of life is impaired in men with chronic prostatitis: the Chronic Prostatitis Collaborative Research Network. J Gen Intern Med2001; 16: 656. Google Scholar 71 : Stress-induced bladder mast cell activation: implications for interstitial cystitis. J Urol1997; 157: 669. Link, Google Scholar 72 : Chronic fatigue syndrome: identification of distinct subgroups on the basis of allergy and psychologic variables. J Allergy Clin Immunol1998; 102: 222. Google Scholar 73 : Interleukin-10-deficient mice develop chronic enterocolitis. Cell1993; 75: 263. Google Scholar 74 : Interleukin 10 genotypes in irritable bowel syndrome: evidence for an inflammatory component?. Gut2003; 52: 91. Google Scholar 75 : Superantigens of gram-positive bacteria: structure-function analyses and their implications for biological activity. Curr Opin Microbiol1998; 1: 56. Google Scholar From the Department of Urology, Temple University School of Medicine, Philadelphia, Pennsylvania© 2004 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byDone J, Rudick C, Quick M, Schaeffer A and Thumbikat P (2012) Role of Mast Cells in Male Chronic Pelvic PainJournal of Urology, VOL. 187, NO. 4, (1473-1482), Online publication date: 1-Apr-2012.Nickel J, Roehrborn C, Montorsi F, Wilson T and Rittmaster R (2011) Dutasteride Reduces Prostatitis Symptoms Compared With Placebo in Men Enrolled in the REDUCE StudyJournal of Urology, VOL. 186, NO. 4, (1313-1318), Online publication date: 1-Oct-2011.Wei X, Zhang G, Yuan H, Ding X, Li S, Zhang X and Hou J (2010) Detection and Quantitation of Soluble B7-H3 in Expressed Prostatic Secretions: A Novel Marker in Patients With Chronic ProstatitisJournal of Urology, VOL. 185, NO. 2, (532-537), Online publication date: 1-Feb-2011.Anderson R, Orenberg E, Morey A, Chavez N and Chan C (2009) Stress Induced Hypothalamus-Pituitary-Adrenal Axis Responses and Disturbances in Psychological Profiles in Men With Chronic Prostatitis/Chronic Pelvic Pain SyndromeJournal of Urology, VOL. 182, NO. 5, (2319-2324), Online publication date: 1-Nov-2009.Pontari M (2009) Chronic Prostatitis/Chronic Pelvic Pain: The DiseaseJournal of Urology, VOL. 182, NO. 1, (19-20), Online publication date: 1-Jul-2009.Chuang Y, Yoshimura N, Huang C, Wu M, Chiang P and Chancellor M (2008) Intraprostatic Botulinum Toxin A Injection Inhibits Cyclooxygenase-2 Expression and Suppresses Prostatic Pain on Capsaicin Induced Prostatitis Model in RatJournal of Urology, VOL. 180, NO. 2, (742-748), Online publication date: 1-Aug-2008.Krieger J (2008) Editorial CommentJournal of Urology, VOL. 179, NO. 5, (1862-1862), Online publication date: 1-May-2008.Chen J, Zhao H and Xu Z (2018) The Prostate has Secretory Dysfunction for Category IIIA and IIIB ProstatitisJournal of Urology, VOL. 177, NO. 6, (2166-2169), Online publication date: 1-Jun-2007.Giubilei G, Mondaini N, Minervini A, Saieva C, Lapini A, Serni S, Bartoletti R and Carini M (2018) Physical Activity of Men With Chronic Prostatitis/Chronic Pelvic Pain Syndrome Not Satisfied With Conventional Treatments—Could it Represent a Valid Option? The Physical Activity and Male Pelvic Pain Trial: A Double-Blind, Randomized StudyJournal of Urology, VOL. 177, NO. 1, (159-165), Online publication date: 1-Jan-2007.Chuang Y and Chancellor M (2018) The Application of Botulinum Toxin in the ProstateJournal of Urology, VOL. 176, NO. 6, (2375-2382), Online publication date: 1-Dec-2006.Nickel J, Shoskes D, Wang Y, Alexander R, Fowler J, Zeitlin S, O'Leary M, Pontari M, Schaeffer A, Landis J, Nyberg L, Kusek J and Propert K (2018) How Does the Pre-Massage and Post-Massage 2-Glass Test Compare to the Meares-Stamey 4-Glass Test in Men With Chronic Prostatitis/Chronic Pelvic Pain Syndrome?Journal of Urology, VOL. 176, NO. 1, (119-124), Online publication date: 1-Jul-2006.ANDERSON R, WISE D, SAWYER T and CHAN C (2018) INTEGRATION OF MYOFASCIAL TRIGGER POINT RELEASE AND PARADOXICAL RELAXATION TRAINING TREATMENT OF CHRONIC PELVIC PAIN IN MENJournal of Urology, VOL. 174, NO. 1, (155-160), Online publication date: 1-Jul-2005.Related articlesJournal of Urology9 Nov 2018Mechanisms in Prostatitis/Chronic Pelvic Pain Syndrome Volume 172Issue 3September 2004Page: 839-845 Advertisement Copyright & Permissions© 2004 by American Urological Association, Inc.Keywordsnerve growth factorpelvic painprostatecytokinesprostatitisMetricsAuthor Information MICHEL A. PONTARI More articles by this author MICHAEL R. RUGGIERI More articles by this author Expand All Advertisement PDF downloadLoading ...