Immunological Mechanisms Underlying Chronic Pelvic Pain and Prostate Inflammation in Chronic Pelvic Pain Syndrome

Abstract

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is the most common urologic morbidity in men younger than 50 years and is characterized by a diverse range of pain and inflammatory symptoms, both in type and severity, that involve the region of the pelvis, perineum, scrotum, rectum, testes, penis, and lower back. In most patients, pain is accompanied by inflammation in the absence of an invading infectious agent. Since CP/CPPS etiology is still not well established, available therapeutic options for patients are far from satisfactory for either physicians or patients. During the past two decades, chronic inflammation has been deeply explored as the cause of CP/CPPS. In this review article, we summarize the current knowledge regarding immunological mechanisms underlying chronic pelvic pain and prostate inflammation in CP/CPPS. Cumulative evidence obtained from both human disease and animal models indicate that several factors may trigger chronic inflammation in the form of autoimmunity against prostate, fostering chronic prostate recruitment of Th1 cells, and different other leukocytes, including mast cells, which might be the main actors in the consequent development of chronic pelvic pain. Thus, the local inflammatory milieu and the secretion of inflammatory mediators may induce neural sensitization leading to chronic pelvic pain development. Although scientific advances are encouraging, additional studies are urgently needed to establish the relationship between prostatitis development, mast cell recruitment to the prostate, and the precise mechanisms by which they would induce pelvic pain.

CaMK4‐dependent phosphorylation of Akt/mTOR underlies Th17 excessive activation in experimental autoimmune prostatitis

“…6 The etiology of CP/ CPPS is still unclear, and the possible mechanisms associated with CP/CPPS include defective urothelial integrity and function, pelvic floor muscle spasm or tenderness, peripheral and central sensitization and neuroplasticity, and autoimmune imbalance. [7][8][9][10] By amplifying inflammation, interleukin (IL)-17Aproducing T helper 17 (Th17) cells play a crucial role in the development and progression of several autoimmune diseases, such as multiple sclerosis (MS) 11 and systemic lupus erythematosus (SLE). 12 Some studies have reported controversial results regarding the role of Th17 cells in the development of CPPS.…”

Upregulation of TRPV1 in spinal dorsal root ganglion by activating NGF‐TrkA pathway contributes to pelvic organ cross‐sensitisation in rats with experimental autoimmune prostatitis

“…There are many types of experimental rodent prostatitis models including spontaneous prostatitis, miscellaneous prostatitis, hormone‐associated prostatitis and immune‐induced prostatitis (Vykhovanets, Resnick, Maclennan, & Gupta, ). EAP is the most commonly used model to mimic CP⁄CPPS since its typical characteristics are consistent with CP⁄CPPS (Breser et al, ). EAP is induced by multipoint subcutaneous injection of prostate antigen with an adjuvant, leading to T‐cell activation and inflammatory cell infiltration of the prostate gland (Kurita, Yamaguchi, Okamoto, Kotera, & Oka, ).…”

“…We hypothesised that TRPV1 plays a significant role in CP/CPPS‐induced pain. A rat model of experimental autoimmune prostatitis (EAP) has been used to study CP/CPPS for decades and has proven valid to mimic human CP⁄CPPS (Breser, Salazar, Rivero, & Motrich, ). We studied the expressions of TRPV1 in the prostate, bladder and dorsal root ganglion (DRG) of EAP rats to elucidate the pathogenesis of CP/CPPS.…”

„Old Friends“, Immunregulation und Stressresilienz

“…Mentale Störungen gehen mit einer erhöhten Immunsystem(re)aktivität einher Viele, wenn nicht gar alle der stressassoziierten somatischen und psychiatrischen Erkrankungen [76][77][78][79][80][81][82] einschließlich PTBS, generalisierte Angststörung (GAS), Panikstörung, Phobien (Agoraphobie, Sozialphobie usw.) [83,84], Depression [85][86][87], Burnout [88,89], chronisches Erschöpfungssyndrom [90][91][92] und Schizophrenie [93], gehen mit einem über(re)aktiven Immunsystem und chronischen unterschwelligen Entzündungen einher.…”