title: Damage to the bladder neck alters autonomous activity and its sensitivity to cholinergic agonists.
abstract: OBJECTIVE
  To identify and describe changes to the motor component of the motor/sensory system, which contributes to sensation during the filling phase of the micturition cycle, as a result of surgically induced bladder pathology, i.e. damage to the bladder neck and outlet obstruction.
  
  
  METHODS
  Adult male guinea pigs (294-454 g) were assigned initially into three groups: (i) normal guinea pigs with no surgical intervention (control, seven); (ii) guinea pigs which, with full surgical anaesthesia, had a silver ring implanted around the bladder neck (obstructed, 13); and (iii) guinea pigs operated to expose the bladder neck but with no implantation of a ring (sham, six). At 2-4 weeks after surgery the bladders were isolated, weighed and the pressure recordings used to identify autonomous activity.
  
  
  RESULTS
  The bladder weights in all operated groups, including the sham, were greater than controls. Bladder weights in the obstructed guinea pigs varied considerably, reflecting the degree of pathological change. Consequently, bladders from this group were divided into those with high (OBH) and those with low bladder weight (OBL). The mean (sd) amplitudes of the autonomous contractions were 1.1 (0.1), 10.8 (1.8), 11.4 (2.5) and 17.1 (4.0) cmH(2)O in control, sham, OBL and OBH bladders, respectively, indicating a progressive alteration in function with the pathology. The changes in the sham group suggested that the pathological changes were not the result of obstruction but damage to the bladder neck, the implantation of the silver rings exacerbating the damage. There were episodes of rapid phasic activity (bursts) in 10 of 13 of the ring-implanted bladders, and in two of six in the sham group, but never in controls. Neither the autonomous activity nor the bursts were affected by tetrodotoxin (1 microm) or atropine (3 microm) but they were abolished by noradrenaline (3 microm). In control bladders, adding the muscarinic agonist arecaidine produced a transient acceleration of phasic activity and increased the amplitude of the contractions. There was a similar acceleration of activity in all the operated groups but the concentrations needed to achieve an increase in frequency were significantly lower, the relative sensitivity to arecaidine being OBH >/= OBL > sham > control.
  
  
  CONCLUSIONS
  The mechanism involved in controlling the frequency of the motor component of the motor/sensory system, the 'pacemaker', appears to become progressively 'supersensitive' to cholinergic stimulation with the development of pathology. These observations are discussed in relation to the motor/sensory system and the origins of sensation in the bladder. The argument is proposed that damage to the bladder neck, not obstruction per se, results in altered nonmicturition activity which contributes to increased afferent output. In turn this contributes to the increased sensations of urge associated with bladder dysfunction. The cholinergic regulation of this altered 'pacemaker' might be the target for one of the therapeutic actions of anticholinergic drugs.
authors.affiliation: Department of Urology, University Hospital Maastricht, Maastricht, The Netherlands.
authors.forename: Rik
authors.initials: R
authors.lastname: de Jongh
authors.forename: Gommert A
authors.initials: GA
authors.lastname: van Koeveringe
authors.forename: Philip E V
authors.initials: PE
authors.lastname: van Kerrebroeck
authors.forename: Marjanne
authors.initials: M
authors.lastname: Markerink-van Ittersum
authors.forename: Jan
authors.initials: J
authors.lastname: de Vente
authors.forename: James I
authors.initials: JI
authors.lastname: Gillespie
mesh_terms: D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D018679:Cholinergic Agonists / Q000494:pharmacology*; D006168:Guinea Pigs; D008297:Male; D012677:Sensation / Q000187:drug effects*; D012678:Sensation Disorders / Q000503:physiopathology*; D001743:Urinary Bladder / Q000187:drug effects* / Q000294:innervation* / Q000503:physiopathology / Q000601:surgery; D001748:Urinary Bladder Neck Obstruction / Q000503:physiopathology*