Mechanosensitive properties of pelvic nerve afferent fibers innervating the urinary bladder of the rat

Abstract

1. Single-unit activity was recorded from S1 dorsal root afferent fibers in pentobarbital-anesthetized rats. In 25 experiments, 245 afferent fibers were identified by electrical stimulation of the pelvic nerve. Fifty-two percent were C fibers (conduction velocity: 1.70 +/- 0.04 m/s; mean +/- SE) and 48% were A delta-fibers (conduction velocity: 11.07 +/- 0.95 m/s). 2. Of 245 pelvic nerve afferent fibers, 92 (38%) responded to noxious urinary bladder distension (UBD; 80 mmHg); 57 of these fibers were C fibers and 35 were A delta-fibers. Forty-four fibers responded to colorectal distension (CRD; 80 mmHg); 32 were C fibers and 12 were A delta-fibers. A total of 39 fibers were identified in the anal mucosa; 3 were C fibers and 36 were A delta-fibers. Seventy fibers (28%) in these experiments were unresponsive to either UBD or CRD or to probing of the anal mucosa; 32 were unmyelinated C fibers and 38 were A delta-fibers. 3. Reproducibility of responses to repeated UBD (80 mmHg, 20 s; 8 trials at 4-min intervals) was tested in 10 fibers. In nine fibers, responses to repeated distension did not change; one fiber exhibited a progressive decrease in response magnitude after the third trial. 4. Of the 92 afferent fibers that responded to UBD, 45 were further characterized for responses to graded intensities of UBD. Forty fibers had some resting activity (1.7 +/- 0.3 impulses/s) and five fibers exhibited no ongoing activity. The response to UBD adapted slowly during the 20-s period of phasic UBD or during slow isotonic filling of the bladder. 5. The stimulus-response function (SRF) of fibers (n = 45) to graded UBD was monotonic < or = 80 mmHg. Thresholds for responses were determined after extrapolation of the least-squares linear regression line to the ordinate, and varied between 0 and 45 mmHg. The frequency distribution profile of thresholds revealed two populations of pelvic nerve afferent fibers in the urinary bladder: a larger group (n = 36) of low-threshold (LT) fibers (5.7 +/- 1.0 mmHg) and a smaller group (n = 9) of high-threshold (HT) fibers (34 +/- 2.5 mmHg). 6. Responses of four LT fibers to graded UBD were tested before and 30 min after instillation of 0.5 ml of 0.5% acetic acid (pH 3) into the bladder. The mean threshold for response of these fibers before instillation of acetic acid (9.4 +/- 3.1 mmHg) more than doubled (to 22.3 +/- 6.7 mmHg) after instillation of acetic acid.(ABSTRACT TRUNCATED AT 400 WORDS)

Differential Responses of Bladder Lumbosacral and Thoracolumbar Dorsal Root Ganglion Neurons to Purinergic Agonists, Protons, and Capsaicin

“…Most LS bladder neurons were small or medium in size based on capacitance, a finding consistent with an immunohistochemical study of S1 bladder neurons (Yohimura et al, 2003) and electrophysiological evidence that 50 -70% of pelvic nerve bladder afferents conduct in the C-fiber range (Sengupta and Gebhart, 1994;Shea et al, 2000). In contrast, we found that TL bladder neurons were medium to large in size, although Ͼ90% of hypogastric/lumbar splanchnic nerve fibers are unmyelinated based on conduction velocity (Nadelhaft and Vera, 1991).…”

“…Thus, IB4-positive neurons comprised 48.8 Ϯ 2.5% (n ϭ 3) and 54.3 Ϯ 3.8% (n ϭ 3) of all LS and TL DRG neurons in the samples studied, respectively ( p Ͼ 0.05). Approximately 50 -70 and 96% of rat bladder pelvic and hypogastric/splanchnic afferents, respectively, have slow conduction velocities consistent with the absence of myelination (Nadelhaft and Vera, 1991;Sengupta and Gebhart, 1994;Shea et al, 2000). To characterize bladder sensory neurons further, we applied IB4 after examination of neurons as described above (Fig.…”

Convergence of bladder and colon sensory innervation occurs at the primary afferent level

“…Similar findings were also noted by Berkley et al, (1990), and most recently, by Malykhina et al, (2004) who have also begun physiologically characterizing dually-labeled DRG neurons projecting to both the bladder and colon. Sengupta and Gebhart (1994) reported no evidence of individual sacral dorsal root afferents responding to distension of both the colon and bladder, however it is possible that afferents innervating more than one organ are either not responsive to mechanical stretch (e.g. they are mucosal or serosal afferents (Brierley et al 2004)) or that they are "silent" nociceptors, which become mechanically-sensitive following inflammation or other insult.…”

Neural Control of the Lower Urinary Tract

“…In rats, Sengupta and Gebhart (561) reported that both Aδ-and C-fiber afferents are mechanosensitive and respond to bladder distension (Fig. 2B).…”

“…Chronic conditions that involve continuous tissue inflammation or irritation can induce changes in sensory pathways that lead to hyperalgesia (heightened response to painful stimuli) and allodynia (pain in response to normally nonpainful stimuli). Thus, continuous tissue inflammation in visceral organs such as the bladder can lead to sensitization of afferent nerves and increased afferent nerve responses to both noxious and nonnoxious stimuli (251,561). In a rat model of chronic cystitis induced by cyclophosphamide or hydrochloric acid, it has been shown that capsaicin-sensitive bladder afferent neurons increase their excitability due to decreased density of A-type K + (K A ) currents, associated with the decreased expression of the Kv1.4 α-subunit (260,703).…”