PubMed · 14334069
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F LOYUDICE, J SIVORI. 1964-10-21. [INTESTINAL PACEMAKER].. https://pubmed.ncbi.nlm.nih.gov/14334069/
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The aim of this study is to evaluate the potency of piboserod (SB 207266), a selective 5-HT(4) receptor antagonist, at inhibiting the 5-HT(4)-mediated potentiating effect of serotonin (5-HT) on the neurally-mediated contractile responses of human detrusor strips to electrical field stimulations (EFS). Strips of human detrusor muscle were mounted in Krebs-HEPES buffer under a resting tension of 500 mg and EFS (20 Hz, 1 ms duration at 300 mA for 5 s) was applied continuously at 1 min intervals. After stabilization of the EFS-induced contractions, concentration-response curves to 5-HT (0.1 nM-100 microM) were constructed in the absence or presence of 1 or 100 nM of piboserod. The experiments were performed in the presence of methysergide (1 microM) and ondansetron (3 microM) to block 5HT(1)/5HT(2) and 5-HT(3) receptors, respectively. 5-HT potentiated the contractile responses to EFS of human bladder strips in a concentration-dependent manner, with a maximum mean of 60.0+/-19.9% of the basal EFS-evoked contractions. Piboserod did not modify the basal contractions but concentration-dependently antagonized the ability of 5-HT to enhance bladder strip contractions to EFS. In presence of 1 and 100 nM of piboserod, the maximal 5-HT-induced potentiations were reduced to 45.0+/-7.9 and 38.7+/-8.7%, respectively. A mean apparent antagonist dissociation constant value (K(B)) of 0.56+/-0.09 nM was determined. These data show the ability of piboserod to antagonize with high potency the enhancing properties of 5-HT on neurally-mediated contractions of isolated human bladder strips. Therefore, the 5-HT(4) receptor might represent an attractive pharmacological target for the treatment of overactive bladder.
The sensory territories of different cutaneous fascicles of the superficial radial nerve were delineated by microneurography at the level of the distal forearm in humans. Three fascicular patterns were found at this level: one supplying the dorsum of the radial aspect of the dorsum of the hand over the first dorsal interosseous space; another supplying the lateral aspect of the first metacarpal extending to the lateral aspect of the thumb; and a third innervating the second interosseous space and the proximal phalanx of the index and middle fingers. The compound fascicular territory is comparable to the classical territory described for the superficial radial nerve. Intraneural microstimulation of individual fascicles did not evoke paraesthesiae or pain beyond their fascicular territory, regardless of the stimulus intensity. We conclude that the superficial radial nerve at the forearm in man is composed of only three fascicles, as shown by the present study and from previous anatomical work. Referred pain seems related to nerve activity in afferent fibres from fascicles supplying deep tissues and muscles, not from cutaneous afferents.
The aim of the study was to investigate how variable fibre geometry influences the excitation and blocking threshold of an undulating peripheral nerve fibre. The sensitivity of the excitation and blocking thresholds of the nerve fibres to various geometric and stimulation parameters was examined. The nerve fibres had a spiral shape (defined by the undulation wavelength, undulation amplitude and phase), and the internodal length varied. Diameter-selective stimulation of nerve fibres was obtained using anodal block. Simulation was performed using a two-part simulation model: a volume conductor model to calculate the electrical potential distribution inside a tripolar cuff electrode and a model of a peripheral undulating human nerve fibre to simulate the fibre response to stimulation. The excitation threshold of the undulating fibres was up to 100% higher than the excitation threshold of the straight fibres. When a nerve was stimulated with long pulses, which are typically applied for anodal block (> 400 micros), the blocking threshold of the undulating fibres was up to four times higher than the blocking threshold of the straight fibres. Dependencies of the excitation threshold on geometric and stimulation parameters were the same as for a straight fibre. Dependencies of the blocking threshold on geometric and stimulation parameters were different compared with a straight fibre. Owing to the fibre undulation and variable internodal length, the blocking threshold and the minimum pulse duration to obtain anodal block were generally different in the proximal and distal directions. Owing to variable fibre geometry, the excitation threshold varied by up to +/- 40% of the mean value, and the blocking threshold varied by up to +/- 60 % of the mean value. Owing to undulation, the blocking threshold of large fibres could be higher than the blocking threshold of small-diameter fibres, even if they had the same geometry. The results indicate that, during skeletal muscle stretching and contracting or during variation in joint angle, the excitation and blocking thresholds of the nerve fibres change owing to variations in fibre geometry. A straight fibre model could be too simple for modelling the response of peripheral nerve fibres to electrical stimulation.