PHYSIOLOGICAL AND MORPHOMETRIC STUDIES INTO THE PATHOPHYSIOLOGY OF DETRUSOR HYPERREFLEXIA IN NEUROPATHIC PATIENTS

The in vitro responses of isolated detrusor strips obtained from neuropathic patients with neuropathic bladder dysfunction were found to be supersensitive to both carbachol [ED(50) 1.2 x 10(-6) M. versus 2.5 x 10(-6) M. in control strips; p < 0.005] and potassium chloride [ED(50) 41.8 mM. versus 49.3 mM. in control strips, p < 0.05]. There were no significant differences in the frequency-response curves obtained with intramural nerve stimulation. However, expressed as a percentage of the maximal response with carbachol, the maximal responses to intramural nerve stimulation in neuropathic strips were reduced [58.3 +/- 21% versus 74.4 +/- 18% for control strips; p < 0.005, Student t test]. Morphometric studies revealed a lower density of 'presumptive' cholinergic nerves in neuropathic detrusor (1.0 +/- 1.4 x 10(-4) mu m.(-2) compared with 3.2 +/- 1.3 x 10(-4) mu m.(-2) in controls, p < 0.05, Mann Whitney U test). The combined physiological and morphometric results were in keeping with a state of postjunctional supersensitivity of neuropathic detrusor secondary to a partial parasympathetic denervation of the smooth muscle. This may be an important factor in the etiology of detrusor hyperreflexia. The contractility of neuropathic tissue in response to field stimulation was found to be much lower than normal (2.4 +/- 1.5 g./10 mg. versus 5.9 +/- 3.0 g./10 mg., p < 0.001; Mann Whitney U test). This reduced contractility to neuronal stimulation might be responsible for some of the characteristics of bladder dysfunction that are seen in patients with similar neurological conditions.