Th1-Th17 Cells Contribute to the Development of Uropathogenic Escherichia coli-Induced Chronic Pelvic Pain

Abstract

The etiology of chronic prostatitis/chronic pelvic pain syndrome in men is unknown but may involve microbes and autoimmune mechanisms. We developed an infection model of chronic pelvic pain in NOD/ShiLtJ (NOD) mice with a clinical Escherichia coli isolate (CP-1) from a patient with chronic pelvic pain. We investigated pain mechanisms in NOD mice and compared it to C57BL/6 (B6) mice, a strain resistant to CP-1-induced pain. Adoptive transfer of CD4+ T cells, but not serum, from CP-1-infected NOD mice was sufficient to induce chronic pelvic pain. CD4+ T cells in CP-1-infected NOD mice expressed IFN-γ and IL-17A but not IL-4, consistent with a Th1/Th17 immune signature. Adoptive transfer of ex-vivo expanded IFN-γ or IL-17A-expressing cells was sufficient to induce pelvic pain in naïve NOD recipients. Pelvic pain was not abolished in NOD-IFN-γ-KO mice but was associated with an enhanced IL-17A immune response to CP1 infection. These findings demonstrate a novel role for Th1 and Th17-mediated adaptive immune mechanisms in chronic pelvic pain.

Visceral Pain

“…The prostate is innervated by the lumbar splanchnic and pelvic nerves and thus the lower abdomen/pelvic area is the area to which sensation is referred. In this model, three behaviors were described as representative of referred hypersensitivity to probing: (1) sharp retraction of the abdomen; (2) immediate licking or scratching of the area of stimulation; and/or (3) jumping (Quick et al 2013). Response frequency of withdrawal responses was calculated as the percentage of positive responses to probing.…”

“…Response frequency of withdrawal responses was calculated as the percentage of positive responses to probing. Quick et al (2013) also tested ''secondary'' hyperalgesia at a distant site, the plantar hind paw, using von Freylike filaments and an up-down method where testing is started with a 0.04 g filament and subsequently increased in ascending order until a positive response is observed (e.g., either a sharp withdrawal of the paw or licking of the paw), after which the previous weaker filament is applied and, if no response is observed, the next stronger filament is applied (Chaplan et al 1994). Exploratory Activity.…”

Search for Microorganisms in Men with Urologic Chronic Pelvic Pain Syndrome: A Culture-Independent Analysis in the MAPP Research Network

“…The fact that we did not identify any significant alterations in the microbiome of patients with a chronic urologic pain condition can not address the possibility that chronic inflammation and pain my persist after an offending organism has been cleared 26,27 . We have also not ruled out the possibility that various organisms, particularly those localized to VB3, identified in UCPPS participants might influence various symptom changes (e.g., flare status) or are associated with select UCPPS patient subgroups (e.g., patients with differing symptom profiles, natural history, and/or underlying biological characteristics).…”

Kronik Prostatit/Kronik Pelvik Ağrı Sendromunda Etyoloji ve Tanı

“…Lokal olarak prostatta meydana gelen patoloji doku düzeyinde hassasiyet ve basınç oluşturmaktadır. Burada bahsedilen sitokinler ve kemokinler hücre sinyal molekülleridir ve gerek proinflamatuar, gerek inflamatuar gerekse de onarım sürecinde yer alan çok sayıda alt başlıkta incelenmektedir (45)(46)(47)(48)(49)(50). Bu hücre sinyalleri aracılığı ile lökositler artmakta ve ekstraprostatik sekresyonda (EPS) saptanmaktadır.…”