A urethral afferent mediated excitatory bladder reflex exists in humans

Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, United States
Neuroscience Letters (Impact Factor: 2.03). 05/2004; 360(1-2):9-12. DOI: 10.1016/j.neulet.2004.01.001
Source: PubMed


An excitatory reflex between urethral flow receptors and the bladder has been established in animals, but attempts to demonstrate this reflex in humans using urethral fluid flow have been inconclusive. Intraurethral electrical stimulation has recently been shown to generate bladder contractions in animals and was applied to study the presence of an excitatory urethra to bladder reflex in humans. The prostatic urethra was stimulated electrically via a catheter-based electrode in five men with complete spinal cord injury. Bladder contractions were generated in four of five individuals, however, only when the bladder volume was sufficiently large. These results demonstrate the presence of a volume dependent excitatory bladder reflex mediated by urethral afferent nerve fibers and the lumbosacral spinal cord.

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    • "In persons with spinal cord injury (SCI), the spino-bulbo-spinal micturition reflex is interrupted [6] [8] [10] [13], but a spinal reflex mediated by pudendal afferents evokes bladder contractions after SCI in the cat [29] [30] [34] [35] and human [15] [18] [36] [37]. This reflex is mediated by afferents that respond to flow through the urethra [14] [33], and thus a better understanding of the mechanisms involved in this urethral flow-modulated response is important to developing more effective approaches to restore bladder emptying. "
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    ABSTRACT: Although sensory feedback from the urethra plays an integral role in the regulation of lower urinary tract function, little is known about the properties of flow-responsive primary afferent neurons. The purpose of this study was to characterize the activity of sacral afferents that responded to fluid flow through the urethra. Single neuron action potentials were recorded extracellularly from the S1 and S2 dorsal root ganglia in eight cats anesthetized with α-chloralose. 21 of 116 cells responded to urethral flow but not to mechanical palpation of the perineum, 22 responded to both urethral flow and palpation, and 27 responded to palpation only. 34 of the 43 flow-responsive cells exhibited a firing response to 10 ml flow boluses that could be fit using a power function: FR(t)=a×(t)(b)+c, where FR is firing rate, t is time, and a, b and c are constants. In all 34 cells the 'b' term was negative, indicating that the firing rate slowed over the time course of the urethral flow. In 16 of the 24 cells that were recorded during at least four different flow rates, a power function provided a good fit of the relationship between firing rate and flow rate: FR(flow)=k×(flow)(p)+q, where k, p and q are constants. In each of these 16 cells the 'p' term was positive, indicating that the firing rate tended to increase with increases in flow rate. These are the first data to characterize the properties of flow-responsive afferents in the cat, and reveal properties that parallel those of other afferents.
    Neuroscience Letters 03/2012; 516(1):34-8. DOI:10.1016/j.neulet.2012.03.045 · 2.03 Impact Factor
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    • "The inability to distinguish pudendal and autonomic activation in the proximal urethra is of concern for clinical studies investigating the ability to evoke bladder responses via urethral pudendal afferent fiber activation. In a previous study, intraurethral stimulation evoked contractions in persons with spinal cord injuries [14], but effective stimulation locations were 2-4 cm from the bladder neck, and the roles of pudendal and autonomic nerve fibers in the observed response is unclear. "
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    ABSTRACT: Intraurethral electrical stimulation (IES) of pudendal afferent nerve fibers can evoke both excitatory and inhibitory bladder reflexes in cats. These pudendovesical reflexes are a potential substrate for restoring bladder function in persons with spinal cord injury or other neurological disorders. However, the complex distribution of pudendal afferent fibers along the lower urinary tract presents a challenge when trying to determine the optimal geometry and position of IES electrodes for evoking these reflexes. This study aimed to determine the optimal intraurethral electrode configuration(s) and locations for selectively activating targeted pudendal afferents to aid future preclinical and clinical investigations. A finite element model (FEM) of the male cat urethra and surrounding structures was generated to simulate IES with a variety of electrode configurations and locations. The activating functions (AFs) along pudendal afferent branches innervating the cat urethra were determined. Additionally, the thresholds for activation of pudendal afferent branches were measured in alpha-chloralose anesthetized cats. Maximum AFs evoked by intraurethral stimulation in the FEM and in vivo threshold intensities were dependent on stimulation location and electrode configuration. A ring electrode configuration is ideal for IES. Stimulation near the urethral meatus or prostate can activate the pudendal afferent fibers at the lowest intensities, and allowed selective activation of the dorsal penile nerve or cranial sensory nerve, respectively. Electrode location was a more important factor than electrode configuration for determining stimulation threshold intensity and nerve selectivity.
    BMC Urology 05/2010; 10(1):11. DOI:10.1186/1471-2490-10-11 · 1.41 Impact Factor
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    • "The similarity of bladder inhibition by low frequency DNP stimulation in both cats and human subjects (see Introduction), suggests the possibility of analogous excitatory pathways also existing in persons with SCI. The identification of this DNP-mediated spinal micturition pathway will depend on the use of higher stimulation frequencies (> 20 Hz) and more selective activation of nerve fibers by utilizing minimally-invasive methods, such as intraurethral or percutaneous needle stimulation (Gustafson, et al., 2004, Yoo, et al., 2007). "
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    ABSTRACT: Bladder contractions evoked by pudendal nerve stimulation in both spinal intact and spinal transected cats support the possibility of restoring urinary function in persons with chronic spinal cord injury (SCI). However, electrically evoked bladder responses in persons with SCI were limited to transient contractions at relatively low pressures. This prompted the present study, which presents a detailed quantification of the responses evoked by selective stimulation of individual branches of the pudendal nerve at different stimulation frequencies. In spinal intact cats anesthetized with alpha-chloralose, selective frequency-dependent electrical activation of the sensory (2 Hz<or=f<or=50 Hz), cranial sensory (f<or=5 Hz), dorsal genital (f>or=20 Hz) and rectal perineal (f<or=10 Hz) branches of the pudendal nerve evoked sustained bladder contractions dependent on the stimulation frequency. Contractions evoked by selective electrical stimulation resulted in significant increases in voiding efficiency compared to bladder emptying by distension-evoked contractions (p(ANOVA)<0.05). Acute spinal transection abolished reflex bladder contractions evoked by low frequency stimulation of the cranial sensory or rectal perineal branches, whereas contractions evoked by high frequency stimulation of the dorsal genital branch remained intact. This study presents evidence for two distinct micturition pathways (spino-bulbo-spinal vs. spinal reflexes) activated by selective afferent pudendal nerve stimulation, the latter of which may be applied to restore bladder function in persons with SCI.
    Experimental Neurology 07/2008; 212(1):218-25. DOI:10.1016/j.expneurol.2008.04.010 · 4.70 Impact Factor
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