The Spinal Pharmacology of Urinary Function: Studies on Urinary Continence in the Unanaesthetized Rat

  1. Greg Bock Organizer and
  2. Julie Whelan
  1. Paul J. Tiseo and
  2. Tony L. Yaksh

Published Online: 28 SEP 2007

DOI: 10.1002/9780470513941.ch6

Ciba Foundation Symposium 151 - Neurobiology of Incontinence

Ciba Foundation Symposium 151 - Neurobiology of Incontinence

How to Cite

Tiseo, P. J. and Yaksh, T. L. (2007) The Spinal Pharmacology of Urinary Function: Studies on Urinary Continence in the Unanaesthetized Rat, in Ciba Foundation Symposium 151 - Neurobiology of Incontinence (eds G. Bock and J. Whelan), John Wiley & Sons, Ltd., Chichester, UK. doi: 10.1002/9780470513941.ch6

Author Information

  1. University of California, San Diego Medical Center, Department of Anesthesiology, T-018, La Jolla, CA 92093, USA

Publication History

  1. Published Online: 28 SEP 2007

ISBN Information

Print ISBN: 9780471926870

Online ISBN: 9780470513941

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Keywords:

  • spinal pharmacology;
  • bladder distension;
  • somatomotor reflex arcs;
  • peptides;
  • volume-evoked micturition reflex

Summary

The volume-evoked micturition reflex (VEMR) is under the control of a complex vesico-spino-bulbo-spino-vesical reflex arc. When functional this system provides for the storage and retention of urine and its subsequent efficient expulsion by virtue of a joint contraction of the bladder and synergic relaxation of the urethral sphincter. Transection of the spinal cord results in an initial disruption of this organization (areflexia) followed by a time-dependent change in the characteristics of the functioning of this reflex system. The growth of knowledge of the pharmacology of spinal systems has yielded considerable information on the potential spinal neurotransmitter systems and their associated receptors. Given the possible role of such systems in mediating and modulating the VEMR, a reasonable approach has been to investigate the effects of spinally administered agonists and antagonists in unanaesthetized animals in which the VEMR can be examined. Thus, it appears that the initial state of bladder distension is signalled by larger (A type) afferent fibres. After spinal injury and the loss of this supraspinal control, smaller unmyelinated C fibres play a predominant role in controlling this reflex. On stimulation these C fibres release peptides (VIP, CCK, substance P, CGRP) and excitatory amino acids (glutamate). Studies in this laboratory have shown that whereas administration of these peptides is without effect in normal intact rats, the antagonists for glutamate and VIP receptors (but not CCK) produce a dose-dependent increase in spontaneous bladder contractions with a corresponding decrease in the volume required to evoke a VEMR. Other spinal systems, such as those for opioids and GABA, are known to exert modulatory effects upon spinal somatomotor reflex arcs. In the spinal cord these agonists (µ/δ and GABAA/B) produce discrete changes in the VEMR in intact and spinally transected animals. Thus these studies may provide insight into the coordinated mechanisms which govern the VEMR and may also allow the development of pharmacological approaches to managing the dysfunctional bladder.