Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030794 (pelvic pain)
 4,056 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experimental autoimmune prostatitis (EAP) is a murine model of chronic prostatitis/chronic pelvic pain syndrome (CPPS) in men, a syndrome characterized by chronic pelvic pain. We have demonstrated that chemokine ligands CCL2 and CCL3 are biomarkers that correlate with pelvic pain symptoms. We postulated that CCL2 and CCL3 play a functional role in CPPS and therefore examined their expression in EAP. Upon examination of the prostate 5 days after induction of EAP, CCL2 mRNA was elevated 2- to 3-fold, CCL8 by 15-fold, CCL12 by 12- to 13-fold, and CXCL9 by 2- to 4-fold compared with control mice. At 10 days the major chemokines were CXCL13 and CXCL2; at 20 days CCL2 (1- to 2-fold), CCL3 (2- to 3-fold) and CCL11 (2- to 3-fold); and at 30 days, CCL12 (20- to 35-fold) and smaller increases in CCL2, CCL3, and XCL1. Chemokine elevations were accompanied by increases in mast cells and B cells at 5 days, monocytes and neutrophils at day 10, CD4+ T cells at day 20, and CD4+ and CD8+ T cells at day 30. Anti-CCL2 and anti-CCL3 neutralizing antibodies administered at EAP onset attenuated pelvic pain development, but only anti-CCL2 antibodies were effective therapeutically. CCL2- and its cognate receptor CCR2-deficient mice were completely protected from development of pain symptoms but assumed susceptibility after reconstitution with wild-type bone marrow. CCL3-deficient mice showed resistance to the maintenance of pelvic pain while CCR5-deficient mice did not show any lessening of pelvic pain severity. These results suggest that the CCL2-CCR2 axis and CCL3 are important mediators of chronic pelvic pain in EAP.
 ...
PMID:CCL2 and CCL3 are essential mediators of pelvic pain in experimental autoimmune prostatitis. 2281 70

The cause of chronic pelvic pain in interstitial cystitis/painful bladder syndrome (IC/PBS) remains unclear; autoimmunity is a possible etiology. We have recently shown that injection of a single immunogenic peptide of uroplakin 3A (UPK3A 65-84) induces experimental autoimmune cystitis (EAC) in female BALB/cJ mice that is unique among experimental models in accurately reflecting both the urinary symptoms and pelvic pain of IC/PBS. The aim of this project was to identify the roles of mast cells and mast cell chemoattractant/activator monocyte chemoattractant protein-1 [chemokine (C-C motif) ligand 2 (CCL2)] in the allodynia in this model. We immunized 6- to 8-wk-old female BALB/cJ mice with UPK3A 65-84 peptide and, 5-40 days later, observed increased responses to stimulation of the suprapubic abdominal and hindpaw surfaces with von Frey monofilaments compared with mice injected with adjuvant alone. Suprapubic and hindpaw tactile allodynia responses by EAC mice were blocked by instillation of lidocaine into the bladder but not by lidocaine in the uterus, confirming the bladder as the source of the hypersensitivity. Markedly increased numbers of activated mast cells and expression of CCL2 were found in the bladder after immunization with UPK3A 65-84. Hypersensitive responses were inhibited by mast cell stabilizer cromolyn sodium and antagonists of histamine receptors 1 and 2. Furthermore, BALB/cJ mice with deletion of the Ccl2 or chemokine (C-C motif) receptor 2 gene exhibited markedly reduced allodynia and accumulation of mast cells after UPK3A 65-84 immunization. These results show that UPK3A 65-84 immunization causes chronic visceral allodynia and suggest that it is mediated by CCL2-driven mast cell accumulation in the bladder.
...
PMID:Chronic pelvic allodynia is mediated by CCL2 through mast cells in an experimental autoimmune cystitis model. 2520 62

The present study aimed to determine the expression and mediation of interleukin-17 (IL-17) and chemokine ligand 2 (CCL2) in a rat model with experimental autoimmune prostatitis (EAP). A total of 44 Sprague Dawley (SD) rats were used in the present study. Of these, a total of 20 two-month-old SD rats were randomly divided into a normal control (n=10) and a model group (EAP group, n=10). The remaining 24 two-month old SD rats were treated in the same way as EAP rats and subsequently randomly divided into a tacrolimus group (n=8), a celecoxib group (n=8) and a normal saline (NS) control group (n=8). Rats in the EAP and normal control groups underwent the Von Frey filaments behavioral test; rats in the tacrolimus, celecoxib and normal saline groups received a pain test following intervention treatment. Prostate tissues of SD rats in each group were harvested for reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis to observe the expression of IL-17 and CCL2. In the pain-reaction test, the occurrence of abnormal pain in the EAP group was significantly higher compared with the control group (P<0.001). The celecoxib group experienced a significant decrease in pain at day 10 compared with the NS group (P<0.01), while the decrease in pain experienced by the tacrolimus group was only significant at day 30 (P<0.001) and the pain experienced by the NS group decreased slightly over this same period. Results of RT-qPCR and western blot analysis indicated that, compared with the control group, the expression of IL-17 and CCL2 in the prostate tissue of EAP rats was significantly upregulated 50 days following modeling (P<0.05). On day 30 following intervention, the expression of IL-17 and CCL2 in the prostate of rats in the tacrolimus and celecoxib groups was significantly downregulated compared with the NS group (P<0.05). Therefore, the results of the current study demonstrate that IL-17 and CCL2 serve a vital role in the morbidity of the experimental autoimmune prostatitis and may also have a mediation effect on pelvic pain associated with chronic prostatitis.
 ...
PMID:The mediation of interleukin-17 and chemokine ligand 2 in pelvic pain of experimental autoimmune prostatitis. 2867 92

The etiology of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is still unknown. Granulocyte macrophage colony-stimulating factor (GM-CSF) has been shown to play an important role in the development of autoimmune and inflammatory diseases. Here, we investigated the expression and function of GM-CSF in patients with CP/CPPS and in a mouse model of experimental autoimmune prostatitis (EAP). GM-CSF mRNA levels were detected in expressed prostatic secretions samples from patients with CP/CPPS and in prostate tissue from a mouse model of EAP. The expression of GM-CSF receptor in mouse prostate and dorsal root ganglia were determined using PCR and immunohistochemistry. Behavioral testing and inflammation scoring were performed to evaluate the role of GM-CSF in disease development and symptom severity of EAP using GM-CSF knockout mice. mRNA levels of putative nociceptive and inflammatory markers were measured in the prostate after the induction of EAP. Elevated GM-CSF mRNA levels were observed in expressed prostatic secretions samples from patients with CP/CPPS compared with healthy volunteers. GM-CSF mRNA was also significantly increased in prostate tissue of the EAP mice model. The expression of GM-CSF receptors was confirmed in mouse prostate and dorsal root ganglia. GM-CSF knockout mice showed fewer Infiltrating leukocytes and pain symptoms after the induction of EAP. Deletion of GM-CSF significantly diminished EAP-induced increases of chemokine (C-C motif) ligand 2, chemokine (C-C motif) ligand 3, and nerve growth factor mRNA expression. The results indicated that GM-CSF plays a functional role in the pathogenesis of EAP. GM-CSF may function as a signaling mediator for both inflammation and pain transduction in CP/CPPS.
 ...
PMID:Role of GM-CSF in a mouse model of experimental autoimmune prostatitis. 3094 70