REVIEW The role of the prostatic stroma in chronic prostatitis/chronic pelvic pain syndrome Marco Dellabella Æ Giulio Milanese Æ Sandra Sigala Æ Gianluca d’Anzeo Æ Nicola Arrighi Æ Serena Bodei Æ Giovanni Muzzonigro Received: 27 May 2009 / Revised: 17 August 2009 / Accepted: 19 August 2009 / Published online: 11 September 2009 Ó Birkha ¨user Verlag, Basel/Switzerland 2009 Abstract Objective To confirm the hypothesis of prostatic stromal involvement in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Materials and methods A literature review to analyze mechanisms commonly indicated as a cause of CP/CPPS that can interfere with the processes of cell growth of smooth muscle fibrocells and may cause smooth muscle cell hypertrophy, periurethral edema, and inflammation. Results Our review strongly suggests a prevalent stromal involvement, specifically of the smooth muscle cells, in CP/ CPPS physiopathology. The involvement of the endocrine system, in particular the role of estrogens, the neurological pathway mediated by noradrenalin, and the presence of inflammation, support the hypothesis that CP/CPPS could be a disease with a prevalent role of smooth muscle stromal cells rather than glandular structures. Neurogenous inflammation, oxidative stress and psychological factors may be involved in the chronic nature of the disease. Conclusions We believe that new studies regarding chronic prostatitis should also be focused on prostatic stromal involvement in the inflammatory pathway. Keywords Inflammation and hormones Á Inflammatory mediators Á Neuroinflammation Á Pain mechanisms Introduction Prostatitis is a disease that affects approximately 11–16% of men under 50 years old both in the United States and Europe, and the probability that a man will develop pros- tatitis during his lifetime is 50% [1]. The social impact of prostatitis is significant because it results in a reduction in the quality of life akin to that induced by Crohn’s disease and myocardial infarction [2]. Approximately 90% of prostatitis cases are classified as chronic (type II and type III according to NIH classification), and they occur with chronic pelvic pain associated with urinary problems. If a genital-urinary tract infection is not demonstrated as the cause of the chronic prostatitis, chronic pelvic pain syn- drome or chronic nonbacterial prostatitis may be diagnosed, a vague clinical picture from an etiological, physiopathological, and therapeutic point of view, in which the only certainty for the patient is to suffer almost daily pain in the perineum, perineal zone, rectal-prostatic area, testicles, urethra, and upper pubic area, with the possibility of associated obstructive and irritative urinary symptoms. Often the patient also reports sexual problems as an asso- ciated aspect of the ‘‘genital-urinary syndrome.’’ Despite its high incidence, the mechanisms underlying the pathophysiology of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are still not well clarified, and a number of studies have tried to better understand and to catalogue Responsible Editor: G. Geisslinger. M. Dellabella (&) Á G. Milanese Á G. d’Anzeo Á G. Muzzonigro Department of Clinic and Specialistic Sciences-Urology and Andrology, Polytechnic University of the Marche Region, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-G.M. Lancisi-G. Salesi, via Conca 71, 60100 Ancona, Italy e-mail: d.urologia@ao-umbertoprimo.marche.it G. d’Anzeo e-mail: giadanz@alice.it S. Sigala Á N. Arrighi Á S. Bodei Section of Pharmacology, Department of Biomedical Sciences and Biotechnology, University of Brescia Medical School, Brescia, Italy Inflamm. Res. (2009) 58:829–836 DOI 10.1007/s00011-009-0086-7 Inflammation Research