Abstract

BackgroundThe purpose of the present study was to determine how acute adult and/or prior early-in life (EIL; P14-P16) exposure to bladder inflammation affects bladder content of calcitonin gene related peptide (CGRP) and substance P (SP). Estrous cycle influences were also studied in the adult-treatment conditions.MethodsIn Experiment 1, intravesical zymosan or isoflurane anesthesia alone was administered to adult female rats. Bladders and serum were collected 24 hours later during each phase of the estrous cycle. In Experiment 2, zymosan or anesthesia alone was administered EIL and as adults, with bladder tissue collection 24 h later.ResultsIn general, Experiment 1 showed that bladder content of both CGRP and SP was increased by inflammation. This effect was significant when data were collapsed across all phases of the estrous cycle, but was only significant during proestrus when individual comparisons were made during each phase of estrous. Also, adult bladder inflammation significantly reduced estradiol levels. In Experiment 2, bladder content of CGRP and SP was significantly increased in rats receiving EIL and/or adult inflammation. Bladder weights were also significantly increased by inflammation.ConclusionsThese data indicate that bladder CGRP and SP are maximally increased during the proestrus phase of the estrous cycle in inflamed adult female rats. EIL exposure to bladder inflammation alone can also produce an increase in CGRP and SP lasting into adulthood. Therefore, EIL experience with bladder inflammation may predispose an organism to experience a painful bladder disorder as an adult by increasing primary afferent content of CGRP and/or SP.

Highlights

  • The purpose of the present study was to determine how acute adult and/or prior early-in life (EIL; P14-P16) exposure to bladder inflammation affects bladder content of calcitonin gene related peptide (CGRP) and substance P (SP)

  • Groups treated with zymosan showed greater levels of SP than estrous-phase matched anesthesia controls and SP content was significantly greater in inflamed rats when data were collapsed across all phases of the estrous cycle as shown in the inset (p = 0.02)

  • The present studies demonstrate that CGRP and SP are increased by adult bladder inflammation, and that EIL exposure to bladder inflammation alone can produce an increase in CGRP and SP lasting into adulthood

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Summary

Introduction

The purpose of the present study was to determine how acute adult and/or prior early-in life (EIL; P14-P16) exposure to bladder inflammation affects bladder content of calcitonin gene related peptide (CGRP) and substance P (SP). The mechanisms underlying bladder hypersensitivity arising from bladder inflammation have been examined by various investigators through the use of agents such as cyclophosphamide (CYP) [1,2,3,4], zymosan [5,6], turpentine [7] and mustard oil [8,9] These studies indicate that bladder tissue, dorsal root ganglion (DRG), and spinal cord content [1,5,8] of two of the primary neurotransmitters of bladder afferents, calcitonin gene-related peptide (CGRP) and substance P (SP), increase following bladder inflammation and may play a critical role in mediating inflammation-produced bladder hypersensitivity. The goal of Experiment 2 was to evaluate how an EIL episode with bladder inflammation affected adult bladder content of CGRP and SP either with or without additional adult bladder inflammation

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