vasoactive-intestinal-peptide and Urination-Disorders

The lower urinary tract has two main functions, the storage and periodic expulsion of urine, which are regulated by a complex neural control system in the brain and lumbosacral spinal cord. This neural system coordinates the activity of two functional units in the lower urinary tract: (1) a reservoir (the urinary bladder) and (2) an outlet (consisting of bladder neck, urethra and striated muscles of the pelvic floor). During urine storage the outlet is closed and the bladder is quiescent, thereby maintaining a low intravesical pressure over a wide range of bladder volumes. During micturition the outlet relaxes and the bladder contracts to promote the release of urine. This reciprocal relationship between bladder and outlet is generated by visceral reflex circuits, some of which are under voluntary control. Experimental studies in animals indicate that the micturition reflex is mediated by a spinobulbospinal pathway passing through a coordination center (the pontine micturition center) located in the rostral brainstem. This reflex pathway is in turn modulated by higher centers in the cerebral cortex that are presumably involved in the voluntary control of micturition. Spinal cord injury at cervical or thoracic levels disrupts voluntary control of voiding as well as the normal reflex pathways that coordinate bladder and sphincter functions. Following spinal cord injury, the bladder is initially areflexic but then becomes hyperreflexic due to the emergence of a spinal micturition reflex pathway. Studies in animals indicate that the recovery of bladder function after spinal cord injury is dependent in part on plasticity of bladder afferent pathways and the unmasking of reflexes triggered by capsaicin-sensitive C-fiber bladder afferent neurons. The plasticity is associated with changes in the properties of ion channels and electrical excitability of afferent neurons, and appears to be mediated in part by neurotrophic factors released in the spinal cord and the peripheral target organs.

Topics: Adrenergic Fibers; Afferent Pathways; Animals; Brain; Efferent Pathways; Glutamic Acid; Humans; Interneurons; Nerve Growth Factors; Pituitary Adenylate Cyclase-Activating Polypeptide; Potassium Channels; Reflex; Sodium Channels; Spinal Cord; Spinal Cord Injuries; Synaptic Transmission; Tachykinins; Urinary Bladder; Urination Disorders; Vasoactive Intestinal Peptide

The purpose of this study was to elucidate the neuroregulation of sphincteric relaxation by investigating the density of nerves containing acetylcholine, noradrenaline, neuropeptide Y (NPY), galanin, vasoactive intestinal polypeptide (VIP) and calcitonin gene-related peptide (CGRP) in the urethral sphincter in patients without a voiding disorder. The complete urethral sphincter (from the bladder neck to beyond the striated external sphincter) was excised from four male and four female adult cadavers and one male and one female fetus. In transverse paraffin or cryostat sections, the above transmitters were identified by histochemical methods. The striated sphincter was densely innervated by cholinergic nerves. Adrenergic nerves next to striated fibers were rare, but were present in all patients. NPY was seen rarely along striated fibers. In the smooth sphincteric component, noradrenaline-, acetylcholine-, NPY- and galanin-reactive nerves were observed frequently. Only functional studies can clarify the clinical implications of these results. Judging from NPY's scarcity in the striated sphincter no efferent function is anticipated. In the smooth component the frequent appearance of NPY, galanin and noradrenaline suggests a regulatory role for these transmitters.

Topics: Acetylcholine; Adult; Aged; Autonomic Nervous System; Cadaver; Calcitonin Gene-Related Peptide; Female; Fetus; Galanin; Humans; Male; Middle Aged; Muscle, Skeletal; Muscle, Smooth; Neuropeptide Y; Neurotransmitter Agents; Norepinephrine; Urethra; Urination; Urination Disorders; Vasoactive Intestinal Peptide

The distribution of nerves containing calcitonin gene-related peptide (CGRP), substance P (SP), neurokinin A (NKA), and vasoactive intestinal peptide (VIP) was examined in the human urinary bladder, using both single- and double-label immunohistochemistry. Nerves containing CGRP and tachykinins were typically present within the subepithelial region, encircling intramural ganglia and around blood vessels. These nerves were sparsely distributed, and only very rarely projected to the smooth muscle bundles of the detrusor. In contrast, VIP-containing nerves formed a dense subepithelial plexus and also projected to the detrusor muscle bundles. The double-label studies revealed that approximately 26% +/- 10% of CGRP-immunoreactive nerves also contained SP and NKA, but that no CGRP fibers coexpressed VIP. Conversely, all SP-immunoreactive fibers also contained CGRP, and many coexpressed NKA. At least three neurochemically distinct populations of nerves can therefore be discerned in the human bladder: VIP/-, CGRP/-, and CGRP/SP/ +/- NKA. The density of CGRP and SP-immunoreactive nerves within the subepithelium of 14 women with urodynamically-proven idiopathic detrusor instability was increased by 82% (p = 0.003) and 94% (p = 0.036), respectively, relative to that of 14 control women with no symptoms of frequency or urgency. This effect was not due to an increase in overall nerve density, because immunoreactivity for the general nerve marker, protein gene product, was not significantly different between the two groups (p = 0.21). The results indicate that at least some patients with detrusor instability demonstrate increases in a specific class of nerve fibers containing CGRP and SP. These peptides are characteristic of sensory neurons in a number of species, suggesting that abnormalities in the afferent arm of the micturition reflex may be associated with detrusor instability.

Topics: Adult; Aged; Aged, 80 and over; Calcitonin Gene-Related Peptide; Female; Humans; Immunoenzyme Techniques; Middle Aged; Neurokinin A; Neurons, Afferent; Substance P; Tachykinins; Urinary Bladder; Urination Disorders; Vasoactive Intestinal Peptide

In a study of 75 isolated human detrusor muscle strips, spontaneous contractions and an associated sustained rise in basal tension were observed in 43 (57%). Vasoactive intestinal polypeptide (VIP) caused significant reductions in the frequency and amplitude of spontaneous contractions and a fall in basal tension. The results suggest that VIP may have a role as an inhibitor of spontaneous activity in the human detrusor.

Topics: Depression, Chemical; Humans; In Vitro Techniques; Muscle Contraction; Muscle, Smooth; Urinary Bladder; Urination Disorders; Vasoactive Intestinal Peptide