Integrative control of the lower urinary tract: preclinical perspective

Abstract

Storage and periodic expulsion of urine is regulated by a neural control system in the brain and spinal cord that coordinates the reciprocal activity of two functional units in the lower urinary tract (LUT): (a) a reservoir (the urinary bladder) and (b) an outlet (bladder neck, urethra and striated muscles of the urethral sphincter). Control of the bladder and urethral outlet is dependent on three sets of peripheral nerves: parasympathetic, sympathetic and somatic nerves that contain afferent as well as efferent pathways. Afferent neurons innervating the bladder have A-d or C-fibre axons. Urine storage reflexes are organized in the spinal cord, whereas voiding reflexes are mediated by a spinobulbospinal pathway passing through a coordination centre (the pontine micturition centre) located in the brainstem. Storage and voiding reflexes are activated by mechanosensitive A-d afferents that respond to bladder distension. Many neurotransmitters including acetylcholine, norepinephrine, dopamine, serotonin, excitatory and inhibitory amino acids, adenosine triphosphate, nitric oxide and neuropeptides are involved in the neural control of the LUT. Injuries or diseases of the nervous system as well as disorders of the peripheral organs can produce LUT dysfunctions including: (1) urinary frequency, urgency and incontinence or (2) inefficient voiding and urinary retention. Neurogenic detrusor overactivity is triggered by C-fibre bladder afferent axons, many of which terminate in the close proximity to the urothelium. The urothelial cells exhibit 'neuron-like' properties that allow them to respond to mechanical and chemical stimuli and to release transmitters that can modulate the activity of afferent nerves.

Sacral Nerve Stimulation: Neuromodulation for Voiding Dysfunction and Pain

“…9,10 This is not surprising considering the complexity of neurological control of voiding. 11 Voiding function is an integrated function requiring input from the parasympathetic system via the pelvic nerve, the sympathetic system via the hypogastric nerve, and the somatic system via the pudendal nerve innervating the rhabdosphincter. Voluntary control of voiding function depends on the interaction of the cortex and the pontine micturition center, which in turn modulates sacral cord voiding reflexes.…”

Surgical procedures used for post-traumatic neurogenic bladder in a cat: report case

“…In the present case the upper motor neuron lesion probably caused the relaxation fail of the urethral sphincter with bladder outlet obstruction and increased urine volume over time with bladder distention and an atonic detrusor muscle (De Groat, 2006). Conservative therapy of neurogenic bladder dysfunction includes emptying the urinary bladder either manually or by catheterization, measures to prevent urinary tract infections such as antibiotic treatment, and use of drugs to facilitate bladder emptying such as alpha adrenergic antagonists and skeletal muscle relaxants (Lorenz and Kornegay, 2004;Lees, 2005;Tudury et al, 2006;Windaele, 2008).…”

“…In cats, the pelvic, hypogastric and pudendal nerves are associated with the functional control of the bladder and urethra (Lorenz and Kornegay, 2004;De Groat, 2006). The pelvic nerves are responsible for parasympathetic innervation and induce detrusor muscle contraction (Dewey, 2008).…”

“…The neurogenic disturbances of micturition are caused by diseases or injuries of the nervous system as well as disorders of the bladder detrusor muscle, the urethral sphincter or both (Lorenz and Kornegay, 2004;Yoshimura and Chancellor, 2004;Lees, 2005;De Groat, 2006;Dewey, 2008). Depending on the severity and reversibility of the lesion, the functional disturbances of the micturition may be temporary or permanent (Lees, 2005;Tudury et al, 2006).…”

Proof of principle: The effect of antimuscarinics on bladder filling sensations in healthy subjects—A placebo controlled double blind investigation using 4 and 8 mg tolterodine extended release

“…The underlying pathomechanism might be neurogenic, myogenic and/or a resulting dysbalance/dysfunction of the biochemical interaction between the urothelium, neural pathways, interstitial cells and smooth muscle cells, which is still not completely understood. Nevertheless, dysregulation of ACh release and muscarinic receptor expression, not only from and on the presynaptic nerve fibers, but also from and on the urothelium seems to play an important role in the pathogenesis of OAB (Abrams et al, 2006;Andersson, 2004;Andersson and Yoshida, 2003;de Groat, 2006). Antimuscarinics have shown to be beneficial in the therapy of OAB symptoms, most probably due to their influence on ACh-release and ACh-receptor binding (Abrams et al, 2006;Andersson, 2004).…”