1. IntroductionIn the cat, pelvic nerve A-delta afferents from the bladder respond to contraction and distension and are generally regarded as being in series with the smooth muscle. C-afferents are usually insensitive to bladder distension in the normal range of intravesical pressure and volumes, and are sometimes termed silent . However, a few may be sensitized and become sensitive to the normal range of pressures by noxious chemicals, and there is also evidence that A-delta afferents are also sensitized by these noxious agents. The location of many afferent endings, as demonstrated by immunocyto-chemical staining for CGRP, substance P and other neuropeptides, is in the mucosa; but there are no established criteria for the electrophysiological identification of mucosal endings. These mucosal endings fail to develop following neonatal capsaicin treatment, and are probably responsible for the reflex hyperexcitability in the rat bladder that can be induced by intravesical capsaicin and other noxious chemicals, e.g., croton oil, mustard oil, turpentine.The concept of capsaicin-sensitive C-fibre afferents, is now well established; however, there is no electrophysiological evidence from single units as to the types of afferent that respond to capsaicin, or regarding the specificity of action of this chemical.1.1. Objectives and ProtocolThe objective of these experiments was to investigate the mechanical and chemical sensitivities of pelvic afferent neurones from the bladder of the rat. The responses to slow distension and emptying, and to intravesical administration of capsaicin and changes in the concentrations of normal ionic constituents of urine have been examined.Single units have been studied in pentobarbitone-anaesthetised rats; arterial pressure, ETCO 2 % and body temperature were maintained within the normal range. A double lumen cannula was inserted into the bladder via the anterior urethra, for measurement of pressure and for distension and emptying of the viscus. Units were selected by observing a constant latency-evoked spike in a filament of the L6 or S1 dorsal root following stimulation of the pelvic nerve at the bladder base. Considerable effort has been taken to ensure that no rapid or excessive distension of the viscus occurred during these experiments: the bladder was emptied and the catheter remained open to the atmosphere to drain until afferents from the pelvic nerve were recorded; only one filament was recorded during each experiment, and the activities of the unit(s) were often examined for about 4-6 h.The effects of three slow distensions with isotonic neutral saline at 37°C and at constant rate were observed on these units; pressure did not exceed 40 mmHg; the discharge during the emptying phase was also monitored. C fibres were identified as those with conduction velocities less than 1.3 m/s. The responses to contraction of the bladder elicited by ventral root stimulation were also observed in many of the afferents.2. Results2.1. Mechanoreceptors and silent afferentsApprox. one-quarter of the afferents were silent, i.e., they did not respond to the distension: their conduction velocities were mainly in the C-range, but a few had A-delta conduction velocities. The remainder responded to distension, and included A-delta and C-afferents.2.2. Responses to distensionThe distension-sensitive afferents were further investigated to ascertain the threshold pressure at which the spike discharge rate increased above baseline, and by measuring the slope of the pressure-response curve. The range of thresholds to distension in the C-fibre mechanoreceptors overlapped that of the A-delta group, but was higher on average. The slope of the stimulus response curve was less in the C-fibres.2.3. Responses to contractions of the bladderContractions which raised the pressure well above the threshold of distension excited about half of the mechanically-sensitive units that were tested; these were predominantly the fibres with very low pressure thresholds, and most, but not all, of them had A-delta conduction velocities.2.4. Sensitisation with chemicalsSensitisation of mechanoreceptors and silent afferents was attempted by distending the bladder (under the same conditions as described above) using 200-500 mM KCl, and osmolalities up to 2000 mosmol, independently and together. Both increased the slope of the stimulus response curve of the mechanosensitive afferents, and resulted in the development of, or an increase in the rate of, resting discharge. A proportion of the silent afferents became mechanosensitive during the application of the chemical stimulation, and the mechanical thresholds of the sensitised units was within the range of the C-mechanoreceptors.2.5. CapsaicinCapsaicin excited A-delta- and C-mechanosensitive afferents, and the pressure thresholds of these covered the full spectrum seen in normal afferents.3. ConclusionsIt is concluded that the properties of pelvic nerve afferents in the rat differ markedly from those of the cat: many units that respond to distension do not respond to contraction of the viscus, and are sensitised by intravesical administration of chemicals; it is possible that these afferents have endings in the mucosa. About half of the A-delta afferents behave in a manner similar to the in series tension receptors described in the cat; some of the A-delta or C silent units become mechanosensitive following sensitisation. Capsaicin excites A-delta and C afferents with a wide range of thresholds.It appears that some of the silent afferents can be recruited to be come low-threshold mechanoreceptors as a consequence of changing the chemical composition of urine to the extreme limits of normality.