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Purpose: The aim of this work was to study the role of capsaicin-sensitive afferent fibers in modulating the micturition reflex at spinal level in urethane-anesthetized guinea pigs after spinal cord transection at level T3-T4., Materials and Methods: The intravesical effect of capsaicin was investigated in a series of cystometrograms performed in intact and spinalized animals., Results: In both intact and spinalized animals capsaicin, at 30 microM, induced a significant increase of volume threshold only, whereas at 100 microM it induced a complete inhibition of the spinal micturition reflex in 60% and 85% of the animals tested, respectively. This capsaicin inhibitory effect (CIE) was unaffected by intravenous phentolamine and propranolol (0.5 and 1 mg./kg., respectively), indomethacin at 100 nmoles intrathecally (i.t.), the CGRP receptor antagonist hCGRP8-37 (3 nmoles i.t.) and the NK2 receptor selective antagonist GR 94800 (1 nmol. i.t.). However, both naloxone (30 microg. i.t.) and the NK1 antagonist GR 82334 (10 to 20 nmoles i.t.) prevented CIE in the majority of spinalized animals., Conclusions: These results suggest that CIE could be mediated by enkephalines released by dorsal root ganglion neurons through substance P release and subsequent activation of NK1 receptors in acutely spinalized guinea pigs.

Detrusor specimens were obtained from 5 patients affected by interstitial cystitis (IC) and 5 patients with bladder carcinoma (controls). Muscle strips were prepared for in vitro pharmacological studies. In all detrusor strips taken from IC patients, an important portion of the electrically-induced contraction was atropine-resistant. In contrast, atropine-resistance was never observed in control detrusors. H1 and H2 antagonists did not affect noncholinergic contractile response which, conversely, was abolished following desensitization to alpha, beta methylene ATP (APCPP). Detrusor muscle from patients affected by IC exhibited an increase in sensitivity to APCPP and a decrease in sensitivity to acetylcholine with respect to control detrusor. Taken together these results are consistent with the presence of a purinergic neurotransmission in parasympathetic nerve terminals of the urinary bladder affected by IC, probably as a consequence of alterations in the innervation and/or electrical coupling between smooth muscle cells. The sensitivity of IC detrusor muscle to histamine was much lower than that of control detrusor, suggesting a desensitization of histamine receptors present in the bladder wall of IC patients.