Etiology of chronic prostatitis/chronic pelvic pain syndrome: psychoimmunoneurendocrine dysfunction (PINE syndrome) or just a really bad infection?

To review the etiology and pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). A literature review for the years 1985-2012 was performed using the MEDLINE database of the United States National Library of Medicine. The evidence for ongoing infection in men with CP/CPPS is lacking. However, men with CP/CPPS are twice as likely to have had a sexually transmitted disease (STD), and bacteria from men with CP/CPPS may be phenotypically different from those that cause cystitis or acute prostatitis. Evidence continues to support an alteration in both the afferent and efferent autonomic nervous systems. Functional brain imaging suggests changes in the gray matter as well as the importance of the anterior insula and anterior cingulated gyrus in pain processing. Neural function can be modulated by immune and endocrine factors. Alterations in cytokine function and autoimmunity appear to play a role in the immune dysfunction. Alterations in the hypothalamic-pituitary-adrenal axis can mediate the endocrine effects, similar to many other chronic pain conditions. Genetics may play a role in who may develop chronic pain after an initial insult. Finally, any biological changes must then be processed through the psychosocial environment, including the tendency to catastrophize, and degree of spousal support, to produce a given individual patient's pain experience. Infection with atypical bacteria or sequelae of an STD may lead to CP/CPPS in some men. Such a biological insult in the context of alterations in psychoimmunoneurendocrine factors produces the chronic pain experience.