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1.
J Urol ; 164(1): 197-202, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10840459

ABSTRACT

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.


Subject(s)
Antigens/administration & dosage , Behavior, Animal/drug effects , Pelvic Pain/chemically induced , Receptors, Neurokinin-1/physiology , Receptors, Neurokinin-2/physiology , Urinary Bladder/drug effects , Administration, Intravesical , Animals , Benzamides/pharmacology , Capsaicin/pharmacology , Dose-Response Relationship, Drug , Female , Guinea Pigs , Neurokinin-1 Receptor Antagonists , Ovalbumin/immunology , Piperidines/pharmacology , Receptors, Neurokinin-2/antagonists & inhibitors
2.
Neurourol Urodyn ; 17(2): 147-52, 1998.
Article in English | MEDLINE | ID: mdl-9514147

ABSTRACT

We reported previously that substances in interstitial cystitis urine, when infused into the rabbit bladder, induce changes that resemble bladders of interstitial cystitis (IC) patients. Here we report our investigation of the effect of additional molecular weight subfractions of IC urine and lower infusion volume in this rabbit bladder bioassay. Urine was pooled from symptomatic IC patients, asymptomatic IC patients (in remission), and normal volunteers. Two fractions of 20x concentrated urine were obtained for each of the 3 groups: a 10-100-kD fraction and a fraction > 100 kD but <0.22 microm. Six rabbits per group were infused twice per week with 6 ml of 1 of these 6 urine fractions or saline as a control. After 6 weeks, each rabbit was cystoscoped before and after hydrodistension, bladder capacity and urea permeability were determined, and the bladder was removed for histologic examination. A questionnaire revealed a significant difference (P < 0.01) regarding voiding symptom severity between symptomatic IC patients and both normal volunteers and IC patients in remission. There was no statistically significant difference among groups of rabbits in cystoscopic bladder appearance, bladder capacity, urea permeability, or bladder histology. If a urine-borne factor is in part responsible for IC symptoms, the rabbit bladder must be filled with urine to near capacity to be able to detect a difference between IC and normal urine in this rabbit bladder bioassay.


Subject(s)
Cystitis/urine , Urinary Bladder/physiology , Administration, Intravesical , Animals , Compliance , Male , Rabbits , Urine/physiology
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