Chronic bladder pain is becoming more and more prevalent and yet there is a lack of effective treatment because there is so little known about the mechanisms causing this type of pain. A possible etiology of chronic bladder pain is persistent inflammation. It has been proposed that inflammation initiates neurological changes in the bladder and CNS which could lead to sensitization of the bladder to cause chronic pain and frequency. Both autonomic and sensory innervation changes in the periphery can lead to hyperalgesia and allodynia, thus we have chosen to look for autonomic and sensory innervation changes that occur in the bladder in a model of chronic cystitis. / In this study, we used a well established animal model to investigate changes in the peptidergic and parasympathetic innervation of the bladder following chronic bladder inflammation. Adult female Sprague-Dawley rats were injected with either 70mg/kg cyclophosphamide diluted in saline, i.p., once every 3 days or saline. After 10 days, all animals were tested for urinary frequency and number of low volume voids, as well as symptoms of spontaneous pain. At the end of 12 days, all animals were perfused with histological fixatives and the urinary bladders processed for immunofluorescence using antibodies against calcitonin gene-related peptide (CGRP) and the vesicular acetylcholine transporter (VAChT) as markers, respectively, of peptidergic primary afferent fibres and parasympathetic efferent fibres. We show that animals treated with cyclophosphamide had inflamed bladders and displayed high urinary frequency as well as some indicators of spontaneous pain, such as piloerection and a rounded-back posture. Furthermore, they had a significant increase in the density of both parasympathetic and peptidergic sensory fibres in the bladder mucosa and an increase in peptidergic sensory fibres in the detrusor muscle. / Thus from our results, we propose that parasympathetic and sensory peptidergic innervation changes can occur in the bladder following chronic cystitis. Since we observed that the parasympathetic and peptidergic fibres often wrapped around one another or were in close proximity, these two fibre populations may be interacting with each other to lead to and maintain sensitization. These innervation changes may be responsible for prolonged and exacerbated urinary symptoms and may play a role in diseases where there is chronic urinary pain, such as in interstitial cystitis.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.111924 |
| Date | January 2005 |
| Creators | Dickson, Laura Alison. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Pharmacology & Therapeutics.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 002328768, proquestno: AAIMR24656, Theses scanned by UMI/ProQuest. |
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