Research PaperPhasic activation of the external urethral sphincter increases voiding efficiency in the rat and the cat
Introduction
Electrical stimulation of the pudendal nerve is under investigation for restoration of bladder emptying in persons with spinal cord injury (Kennelly et al., 2011, Yoo et al., 2009, Yoo et al., 2011). Selective electrical stimulation of individual branches of the pudendal nerve evokes sustained bladder contractions and increases voiding efficiency (VE) beyond that of distention-evoked reflex voiding in cats (Woock et al., 2008, Yoo et al., 2008a). However, while pudendal nerve stimulation is a promising approach, VE is limited to 60–70% in anesthetized cats (Boggs et al., 2006, Woock et al., 2008, Yoo et al., 2008a), and larger VE is desirable for clinical translation. The objective of the present study was to test the hypothesis that artificial phasic activation of the external urethral sphincter (EUS), as is observed during voiding in rats and dogs, would enhance VE in cats.
Phasic bursting activity in the EUS, which occurs during voiding in rats (Chen et al., 2011, Chen et al., 2012, Kakizaki et al., 1997, Kruse et al., 1990, Peng et al., 2008, Vera and Nadelhaft, 2001) and dogs (Nishizawa et al., 1984a, Nishizawa et al., 1984b), is observed in the electromyogram (EMG) of the striated EUS and as high frequency oscillations (HFOs) in intravesical pressure. While the origin and function of this activity remain unclear, elimination of phasic EUS activity either by transection of the pudendal nerve innervating the EUS in the rat (Cruz and Downie, 2005, Peng et al., 2006) and dog (Nishizawa et al., 1984a) or by neuromuscular blockade in the rat (Conte et al., 1991, Kruse et al., 1993, Maggi et al., 1986, Peng et al., 2006, Vera and Nadelhaft, 2001, Yoshiyama et al., 2000) causes a significant reduction in VE.
We conducted a series of experiments in rats and cats to investigate the hypothesis that introduction of artificial EUS bursting activity by electrical stimulation could increase VE under conditions where such activity was absent. We first conducted a series of experiments in rats to verify the role of phasic EUS bursting in efficient voiding and to test the hypothesis that re-introduction of phasic EUS activity following motor nerve transection could restore efficient voiding. Subsequently, we quantified the effects of introducing phasic EUS bursting activity on bladder contractions and VE in the cat, which, unlike the rat, normally exhibits relaxation of the EUS while voiding (Fedirchuk and Shefchyk, 1993). Finally, in both rats and cats, transection of the sensory branches of the pudendal nerves revealed that phasic EUS activity increased voiding efficiency through a sensory pathway, presumably by amplifying the sensory input to the augmenting reflex (Barrington, 1941). Collectively, these results provide further insight into the function of phasic EUS activity in efficient voiding and highlight a novel approach to increase VE generated by pudendal afferent nerve stimulation.
Section snippets
Materials and methods
All animal care and experimental procedures were reviewed and approved by the Duke University Institutional Animal Care and Use Committee.
Results
Artificial phasic bursting activity of the EUS increased voiding efficiency in both rats and cats, and selective nerve transections revealed that this effect was mediated by sensory feedback via pudendal afferents.
Discussion
Artificial phasic burst activation of the external urethral sphincter (EUS) evoked by electrical stimulation of the pudendal motor branch increased voiding efficiency in both rats and cats. Our initial experiments verified the importance of phasic EUS bursting for efficient voiding in rats. Phasic bursting of the EUS was present during micturition in control conditions (see Fig 1A-B) (Chen et al., 2011, Chen et al., 2012, D'Amico and Collins, 2012, Kakizaki et al., 1997, Kruse et al., 1990,
Conclusions
Phasic bursting activity of the EUS is critical for efficient voiding in rats, and artificial restoration of phasic bursting lost following nerve transection could restore efficient voiding in rats. Imposition of artificial phasic bursting in cats, which normally exhibits EUS relaxation while voiding, was also effective in promoting efficient voiding. In both species phasic EUS activity increased voiding efficiency through activation of pudendal sensory pathways. Phasic bursting is presumably
Acknowledgements
The authors thank Gilda Mills for her assistance during these experiments. This work was supported by a grant from the National Institutes of Health (R01 NS050514).
References (32)
- et al.
Effect of a 5-HT(1A) receptor agonist (8-OH-DPAT) on the external urethral sphincter activity in the rat
J. Formos. Med. Assoc. = Taiwan yi zhi
(2012) - et al.
Simultaneous recording of vesical and urethral pressure in urethane-anesthetized rats: effect of neuromuscular blocking agents on the activity of the external urethral sphincter
J. Pharmacol. Methods
(1991) - et al.
Pontine control of the urinary bladder and external urethral sphincter in the rat
Brain Res.
(1990) - et al.
Role of the pudendal nerves on the dynamics of micturition in the dog evaluated by pressure flow EMG and pressure flow plot studies
J. Urol.
(1984) - et al.
Somato-motor components of the pelvic and pudendal nerves of the female rat
Brain Res.
(1989) - et al.
Urethral flow-responsive afferents in the cat sacral dorsal root ganglia
Neurosci. Lett.
(2012) - et al.
Clozapine inhibits micturition parameters and the external urethral sphincter during cystometry in anesthetized rats
Brain Res.
(2001) - et al.
Multiple pudendal sensory pathways reflexly modulate bladder and urethral activity in patients with spinal cord injury
J. Urol.
(2011) - et al.
Bladder activation by selective stimulation of pudendal nerve afferents in the cat
Exp. Neurol.
(2008) - et al.
Somatic innervation of the feline lower urinary tract
Brain Res.
(2008)