ovalbumin and Pelvic-Pain

Topics: Animals; Antigens; Autoimmune Diseases; Cystitis; Cystitis, Interstitial; Cytokines; Disease Models, Animal; Gene Expression Regulation; Mice; Mice, Transgenic; Ovalbumin; Pelvic Pain; Urinary Bladder; Urination Disorders; Urothelium

Topics: Animals; Chronic Disease; Chronic Pain; Disease Models, Animal; Drug Carriers; Enzyme-Linked Immunosorbent Assay; Immune Tolerance; Inflammation Mediators; Male; Mice; Mice, Inbred C57BL; Nanoparticles; Ovalbumin; Pelvic Pain; Peptides; Polylactic Acid-Polyglycolic Acid Copolymer; Prostatitis; Random Allocation

Bladder inflammation frequently causes cystitis pain and lower urinary tract dysfunction (LUTD) such as urinary frequency and urgency. Although mast cells have been identified to play a critical role in bladder inflammation and pain, the role of mast cells in cystitis-associated LUTD has not been demonstrated. Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and debilitating inflammatory condition of the urinary bladder characterized by the hallmark symptoms of pelvic pain and LUTD. In this study we investigated the role of mast cells in LUTD using a transgenic autoimmune cystitis model (URO-OVA) that reproduces many clinical correlates of IC/BPS. URO-OVA mice express the membrane form of the model antigen ovalbumin (OVA) as a self-antigen on the urothelium and develop bladder inflammation upon introduction of OVA-specific T cells. To investigate the role of mast cells, we crossed URO-OVA mice with mast cell-deficient KitW-sh mice to generate URO-OVA/KitW-sh mice that retained urothelial OVA expression but lacked endogenous mast cells. We compared URO-OVA mice with URO-OVA/KitW-sh mice with and without mast cell reconstitution in response to cystitis induction. URO-OVA mice developed profound bladder inflammation with increased mast cell counts and LUTD, including increased total number of voids, decreased mean volume voided per micturition, and decreased maximum volume voided per micturition, after cystitis induction. In contrast, similarly cystitis-induced URO-OVA/KitW-sh mice developed reduced bladder inflammation with no mast cells and LUTD detected. However, after mast cell reconstitution URO-OVA/KitW-sh mice restored the ability to develop bladder inflammation and LUTD following cystitis induction. We further treated URO-OVA mice with cromolyn, a mast cell membrane stabilizer, and found that cromolyn treatment reversed bladder inflammation and LUTD in the animal model. Our results provide direct evidence for the role of mast cells in cystitis-associated LUTD, supporting the use of mast cell inhibitors for treatment of certain forms of IC/BPS.

Topics: Animals; Autoimmune Diseases; Behavior, Animal; CD8-Positive T-Lymphocytes; Cells, Cultured; Cromolyn Sodium; Cystitis, Interstitial; Cytokines; Disease Models, Animal; Mast Cells; Mice; Mice, Inbred C57BL; Mice, Transgenic; Ovalbumin; Pelvic Pain; Proto-Oncogene Proteins c-kit; RNA, Messenger; Urinary Bladder

To characterize a guinea pig behavior model of bladder pain due to intravesical antigen infusion and to determine the role of neurokinin receptor subtypes in mediating this behavior.. The influence of subtype-selective neurokinin receptor antagonists on increased abdominal licking behavior in response to intravesical antigen infusion in guinea pigs immunized with ovalbumin (OA) was determined.. Intravesical OA infusion for 30 minutes induced a significantly greater frequency (about 3-fold) of abdominal licking behavior than during either the 30 minutes pre-challenge or post challenge saline infusions. Treatment with IP capsaicin 7 to 10 days before OA challenge abolished the intravesical antigen-induced behavior. IP injection of the NK1 receptor antagonist CP 99994 (10 mg./kg. or 30 mg./kg.), 30 minutes pretreatment, inhibited the increase in the average number of abdominal licks during antigen infusion. The 30 mg./kg., but not the 10 mg./kg. dose increased the percent of animals showing antinociceptive activity (defined as 4 or less abdominal licks during the antigen infusion). The NK2 receptor antagonist SR 48968 reduced the antigen-induced abdominal licking behavior at IP doses of 3 and 10 mg./kg. but was ineffective at 1 mg./kg. The NK3 receptor antagonist SB 235375 (30 mg./kg., IP) did not reduce this behavior.. These results suggest a role for activation of NK1 and NK2, but not NK3 receptors, by tachykinins released from capsaicin-sensitive nerves, in the increased abdominal licking behavior response of guinea pigs to intravesical antigen infusion.

Topics: Administration, Intravesical; Animals; Antigens; Behavior, Animal; Benzamides; Capsaicin; Dose-Response Relationship, Drug; Female; Guinea Pigs; Neurokinin-1 Receptor Antagonists; Ovalbumin; Pelvic Pain; Piperidines; Receptors, Neurokinin-1; Receptors, Neurokinin-2; Urinary Bladder