Control of the lower urinary tract is achieved through both branches of the autonomic nervous system (sympathetic and parasympathetic), and the somatomotor branch for the rhabdosphincter. Excellent in depth reviews of this topic may be found in Fowler et al. [1] and de Groat et al. [7]. For the purposes of this chapter, the following brief description should suffice.

During the storage phase of the micturition cycle, active contraction of urethral circumferential smooth muscle and active relaxation of bladder smooth muscle are achieved via sympathetic stimulation of alpha-adrenergic and beta-adrenergic receptors, respectively, via the hypogastric nerves. In this case, the same neurotransmitter, norepinephrine, results in different effects because of regional differences in receptor subtype expression. Also during the storage phase, active tonic contraction of the rhabdosphincter is achieved by special motoneurons residing in Onuf’s nucleus in the sacral spinal cord whose axons course through the pudendal nerve. These neurons are activated by a bladder-to-rhabdosphincter reflex and this reflex is important in maintain continence.

For the most part, bladder filling is not sensed at the conscious level, and these storage reflexes are governed by afferent input from the bladder at the level of the spinal cord. As filling approaches bladder capacity, and therefore approaches triggering of reflex micturition, afferent input from the bladder becomes sensed at the conscious level and inhibition of the pontine micturition reflex center is applied together with conscious activation of the rhabdosphincter while the individual seeks an appropriate environment to void. Once an appropriate environment is found or established, conscious inhibition of the micturition reflex is relaxed and parallel pathways of inhibition of the bladder-to-rhabdosphincter spinal reflex and excitation of the neurons innervating the lower urinary tract within the parasympathetic nucleus allows for voiding to ensue.

Postganglionic parasympathetic neurons that innervate the bladder contain either the paired smooth muscle excitatory transmitters acetylcholine (ACh) and adenosine triphosphate (ATP), neuronal nitric oxide synthase (NO; nitric oxide relaxes smooth muscle), or all of these. The distribution of these transmitters is not compartmentalized between bladder and urethra, as one might have predicted, and regional selectivity (i.e. bladder contraction and urethral smooth muscle relaxation) is achieved by the distribution of soluble guanylate cyclase, the target in smooth muscle for NO. In this case, the urinary bladder smooth muscle does not contain soluble guanylate cyclase, while the urethral circumferential smooth muscle does. It is not the case that ACh and ATP will not contract urethral circumferential smooth muscle, but rather that NO relaxation overcomes these and many, if not all, neurotransmitter- and prostaglandin-induced contractions of this layer of smooth muscle [8, 9].

That NO release in the urethra results in relaxation of urethral circumferential smooth muscle, even in the face of maximal alpha-adrenergic-mediated contraction pairs nicely with the fact that ACh stimulation of the degree experienced during micturition is not blocked by beta-adrenergic-mediated relaxation [10]. Therefore, in the absence of mechanical obstruction (e.g. stricture, pelvic floor prolapse or detrusor sphincter dyssynergia), once triggered, a micturition reflex is ensured. Thus, it is not necessary to shut off reflex sympathetic input to the system as a parallel step, although this may, in fact, occur as an evolutionary redundancy.

The sequence of events for a true micturition event is as follows: Parallel signals descend from the pontine micturition center. One signal is inhibitory to Onuf’s nucleus and stops the bladder-to-rhabdosphincter spinal continence reflex. The other signal is an excitatory signal to the parasympathetic nucleus of the sacral spinal cord, stimulates parasympathetic preganglionic neurons that project to the pelvic ganglia to stimulate, in turn, the parasympathetic postganglionic neurons . The latter neurons project to the bladder and urethra. At the bladder, they cause contraction at the dome that, due to the random fiber orientation, is directed centrally and downward. The longitudinal muscle layers at the bladder base through the proximal 1/2–2/3 of the pelvic urethra also contract, which forces the bladder neck open into a funnel and provides sufficient tension to maintain the funnel shape rather than allowing the base-proximal urethra to balloon out. At the same time, the circumferential smooth muscle of the urethra relaxes, allowing the funneling to occur easily. The net result of longitudinal smooth muscle contraction is both a shortening of the distance between the bladder base and the length of the urethra that does not include longitudinal smooth muscle (i.e. the bladder descends into the pelvic floor) and an expansion of the urethral lumen, both of which reduce resistance to flow.

While this reflex seems capable of doing the job as described once initiated, there are likely modulatory afferent inputs arising from the urethra that refine the duration of descending signal. For example, upon the initiation of the void, urine that enters the proximal urethra may provide positive feedback via chemosensitive, distension sensitive and flow sensitive urethral afferents to promote continued bladder contraction, helping to ensure full emptying. Barrington [11, 12] described three such reflexes that support urethral-to-bladder positive feedback:

The presence of these urethral-to-bladder reflexes remains controversial in humans, and one must recognize that differences in findings from clinical human and preclinical animal studies may reflect testing conditions and/or true species differences. However, if one were to design a system for efficient voiding, one would likely design such a system with such feedback mechanisms in place. It is tempting, therefore, to predict that such reflex pathways would be prevalent across mammalian species, including humans.