vasoactive-intestinal-peptide and Cadaver

Provoked vestibulodynia (PVD) is a chronic pain condition characterized by allodynia localized to the vulvar vestibule. The finding of increased densities of nerve fibers in the vestibular mucosa of patients with PVD has led to the identification of a neuroproliferative subtype. The etiology of PVD, including neuroproliferative vestibulodynia (NPV), is not fully understood. The gross and microscopic innervation of the vulvar vestibule remains incompletely described, despite the preliminary data supporting the role of peripheral innervation in PVD.. To characterize the gross anatomic and microscopic innervation of the vulvar vestibule through cadaveric dissection and immunohistochemistry.. The pudendal nerve and inferior hypogastric plexus (IHP) were dissected using 6 cadaveric donors. Histology and immunohistochemistry were used to confirm patterns of innervation identified gross anatomically. Immunohistochemistry was performed on vestibulectomy specimens obtained from 6 patients diagnosed with NPV and compared with cadaveric vestibular tissues.. Outcomes included (1) dissection of pelvic innervation and (2) immunohistochemical localization of markers for the following: general innervation protein gene product 9.5 (PGP9.5), sensory innervation (calcitonin gene-related peptide), autonomic innervation (vasoactive intestinal polypeptide, tyrosine hydroxylase), neuroproliferation (nerve growth factor [NGF]), and immune activation (C-kit).. Perineal (pudendal) nerve branches were traced to the external wall of the vulvar vestibule. Some anatomic heterogeneity was observed in perineal nerve-branching patterns. Fibers from the IHP were identified in close proximity to the vulvar vestibule. Autonomic and sensory nerve fibers were identified in both patient and cadaveric vulvar vestibule samples. Patient samples were characterized by the proliferation of PGP9.5-positive nerve fibers and C-kit-positive mast cells, which were in proximity to neve bundles and showed coexpression with putative NGF-positive cells. NGF expression was localized to a subset of nerves, including those that demonstrated co-expression of sensory and autonomic nerve markers. Increased densities of autonomic fibers positive for vasoactive intestinal polypeptide and tyrosine hydroxylase were observed in 1 patient sample.. Heterogeneity in gross and microscopic patterns of innervation could explain variability in clinical response to treatment and should be used to inform future therapeutic interventions.. This study used a combination of approaches to elucidate the innervation of the vulvar vestibule, including in NPV. The small sample size is a limitation.. The vulvar vestibule contains both sensory and autonomic innervation, which may originate from the pudendal nerve and IHP. Our results support the existence of a neuroproliferative subtype that is characterized by the proliferation of sensory and autonomic nerve fibers and neuroimmune interactions.

Topics: Cadaver; Female; Humans; Nerve Growth Factor; Tyrosine 3-Monooxygenase; Vasoactive Intestinal Peptide; Vulvodynia

The human internal carotid nerve (ICN) occasionally has a swelling beneath the external opening of the carotid canal. In this study, the presence and distribution of neuronal cells were investigated in the bilateral ICNs of nine human cadavers. Among 44.4% of the cadavers, swellings were detected in the ICN. Their diameters ranged from 1.7 to 3.6 mm (average ± SD = 2.6 ± 0.7 mm). Thirty-eight percent of these swellings were large (diameter > 3 mm) and showed an oval shape. The large swelling contained many neuronal cells. However, the ICNs with or without a swelling <3 mm diameter were mostly free from neuronal cells (93.3%). Only in one human cadaver, the right ICN without a swelling had a small number of neuronal cells. By the present immunohistochemical method, ICN neurons contained catecholamine-synthesizing enzymes and neuropeptides. Dopamine-beta hydroxylase- and tyrosine hydroxylase-immunoreactivity were mostly expressed by ICN neurons. More than half of them also contained neuropeptide Y-immunoreactivity. However, vasoactive intestinal polypeptide-immunoreactive ICN neurons were relatively infrequent. Substance P- and calcitonin gene-related peptide-immunoreactive ICN neurons could not be detected. By the cell size analysis, neuropeptide Y-immunoreactive neurons were significantly smaller than neuropeptide Y-immunonegative neurons in the ICN. The present study suggests that ICN neurons have a sympathetic function in the human.

Topics: Cadaver; Dopamine beta-Hydroxylase; Humans; Neurons; Neuropeptide Y; Tyrosine 3-Monooxygenase; Vasoactive Intestinal Peptide

Although the pelvic autonomic plexus branches are considered to be a mixture of sympathetic and parasympathetic nerves, little is known regarding the composite fibers of the pelvic plexus branches. This study aimed to investigate the immunohistochemical features of sympathetic and parasympathetic nerves in the pelvic autonomic plexus branches.. Using 10 donated elderly male cadavers, the detailed topohistology of nerve fibers at and around the bladder, seminal vesicle, prostate, and rectum was examined. Neuronal nitric oxide synthase (nNOS) and vasoactive intestinal polypeptide (VIP) were used as parasympathetic nerve markers; tyrosine hydroxylase (TH) was used as a sympathetic nerve marker. The myenteric plexus of the colon was utilized as a positive control.. Most nerve fibers in the bladder, seminal vesicle, prostate, and rectum were both nNOS- and TH-positive. Thus, pelvic plexus branches were classified into two types: 1) triple-positive mixed nerves (nNOS+, VIP+, TH+, thick myelinated fibers + or -) and 2) double-positive mixed nerves (nNOS+, VIP-, TH+, thick myelinated fibers + or -). Notably, triple-positive nerves were localized within the posterosuperior part of the plexus (near the rectum) and travelled anteroinferiorly toward the posterolateral corner of the prostate. The posteriorly and inferiorly located nerves were predominantly composed of parasympathetic, rather than sympathetic, fibers. In contrast, nerve fibers within and along the bladder and seminal vesicle contained either no or few VIP-positive nerves. These superiorly located nerves were characterized by clear sympathetic nerve dominance.. The nerves of the pelvic plexus branches were clearly classified into nerves around the bladder and seminal vesicle (VIP-negative) and nerves around the prostate (VIP-positive). Although nNOS- and VIP-positive nerve fibers are candidate cavernous nerves, cavernous nerve identity cannot be definitively concluded for these nerves in the periprostatic region.

Topics: Aged; Aged, 80 and over; Cadaver; Humans; Hypogastric Plexus; Male; Middle Aged; Nerve Fibers; Nitric Oxide Synthase Type I; Prostate; Rectum; Seminal Vesicles; Urinary Bladder; Vasoactive Intestinal Peptide

To describe and discuss the normal anatomy and function of enteric neurons in the esophagus of aged individuals.. We examined ganglion cells in esophagus specimens obtained from 15 elderly cadavers without any macroscopic pathology in the mediastinum and abdomen. Neuronal nitric oxide synthase and vasoactive intestinal polypeptide were used as parasympathetic nerve markers, and tyrosine hydroxylase as a sympathetic nerve marker.. The thoracic and abdominal esophagus contained a well-developed myenteric nerve plexus (S100 protein-positive area) in the intermuscular layer: 0.02-0.03 mm. In comparison with previous data from elderly cadavers, the esophagus carried much fewer ganglion cells than the intestine and colon; sympathetic cells were particular less numerous. Esophageal smooth muscle exhibits a unique mode of peristalsis characterized by a rebound contraction with a long latency after stimulation. This type of peristalsis appears to be regulated by inhibitory, nNOS-positive nerves with a sparse distribution, which seems to account for the long-span peristalsis unique to the esophagus. The extreme sparsity of ganglion cells in the cervical esophagus suggests that enteric neuron-integrated peristalsis, like that in the intestine and colon, is unlikely. Surgical treatment of the esophagus is likely to change or impair these unique features.

Topics: Aged; Aged, 80 and over; Biomarkers; Cadaver; Esophagus; Humans; Immunohistochemistry; Male; Myenteric Plexus; Neurons; Nitric Oxide Synthase Type I; Tyrosine 3-Monooxygenase; Vasoactive Intestinal Peptide

Nerves serving the internal anal sphincter (NIAS) have been described as the lower rectal branches of the pelvic autonomic nerve plexus. However, their topographical anatomy and fiber components have remained unclear.. Using histological sections from ten elderly donated cadavers, we investigated the topographical anatomy and composite fibers of the NIAS using immunohistochemistry for S100 protein, neuronal nitric oxide synthase (nNOS), vasoactive intestinal polypeptide (VIP) and tyrosine hydroxylase (TH).. At the 2-3 o'clock position in the lower rectum, the NIAS originated from nerves at the posterolateral corner of the prostate in males or in the lower paracolpium in females. The nerves ran inferiorly along the internal aspect of the levator ani muscle, and joined branches of the myenteric plexus at a level slightly above the epithelial junction. The NIAS contained both nNOS-positive parasympathetic nerve fibers and TH-positive sympathetic fibers, but VIP-positive fibers were few in number.. The origin of the NIAS at the posterolateral corner of the prostate as well as in the lower paracolpium might be sacrificed or damaged during radical prostatectomy or tension-free vaginal tape insertion. Low anterior resection of rectal cancer will most likely render damage to the NIAS because of its intersphincteric course. Although the nerve composition of the NIAS is characterized by a higher proportion of sympathetic nerve fibers than the myenteric plexus in the large intestine, their role is unclear. However, evaluation of sphincteric function after surgery would appear to be difficult because of the complex control mechanism independent of nerve supply.

Topics: Aged; Aged, 80 and over; Anal Canal; Cadaver; Female; Humans; Male; Nitric Oxide Synthase Type I; S100 Proteins; Tyrosine 3-Monooxygenase; Vasoactive Intestinal Peptide

To identify site-dependent and individual differences in neuronal nitric oxide synthase (nNOS)-positive nerves of the myenteric plexus, we examined full-thickness walls of the stomach, pylorus, duodenum, ileum, colon, and rectum in 7 male and 8 female cadavers (mean ages, 80 and 87 years, respectively).. The areas occupied by nNOS-positive nerve fibers in the myenteric plexus were fragmentary and overlapped with areas occupied by vasoactive intestinal polypeptide-positive fibers. The nNOS-positive fiber-containing areas per 1-mm length of intermuscular space tended to be larger at more anal sites, with positive areas four times greater in the rectum than in the stomach. Interindividual differences in rectal areas were extremely large, ranging from 0.017 mm(2) in one 80-year-old man to 0.067 mm(2) in another 80-year-old man. Similarly, the numbers of nNOS-positive ganglion cell bodies per 1-mm length in the rectum ranged from 4 to 28. These areas and numbers were weakly correlated (r = 0.62; p = 0.02). Interindividual differences in the rectum appeared not to depend on either age or gender.. Anatomic studies using donated cadavers carried the advantage of obtaining any parts of intestine within an individual, in contrast to surgically removed specimens. We speculated excess control of evacuation with laxatives as one of causes of atrophy of the rectal myenteric plexus.

Topics: Aged; Aged, 80 and over; Cadaver; Colon; Duodenum; Female; Humans; Ileum; Immunohistochemistry; Male; Myenteric Plexus; Nitric Oxide Synthase Type I; Pylorus; Rectum; Stomach; Tyrosine 3-Monooxygenase; Vasoactive Intestinal Peptide

Cranial parasympathetic outflow is mediated through the sphenopalatine ganglion (SPG). The present study was performed to examine the expression of the parasympathetic signaling transmitters and their receptors in human and rat SPG. Indirect immunofluorescence technique was used for the demonstration of vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating peptide (PACAP), nitric oxide synthase (NOS), glutamine synthetase (GS), glial fibrillary acidic protein (GFAP), VIP and PACAP common receptors (VPAC1, VPAC2), and PACAP receptor (PAC1). In addition, double labeling was carried out to reveal the co-localization of neurotransmitters. VIP-immunoreactive (-ir) neurons as well as fibers were frequently found in human SPG. Many, homogenously stained NOS-ir cells were found, but no positive fibers. In addition, PACAP-ir was observed in some of the neurons and in fibers. Co-localization was found between VIP and NOS. In rat VIP-, NOS-, and PACAP-ir were found in many neurons and fibers. Co-localization of PACAP and NOS was observed in neurons. PACAP and GS double staining revealed that the PACAP-ir was localized in/close to the cell membrane, but not in the satellite glial cells. PAC1 and VPAC1 immunoreactivity was found in the satellite glial cells of both human and rat. Western blot revealed protein expression of PAC1, VPAC1, and VPAC2 in rat SPG. The trigeminal-autonomic reflex may be active in migraine attacks. We hypothesized that VIP, PACAP, NOS, PAC1, VPAC1, and VPAC2 play a role in the activation of parasympathetic cranial outflow during migraine attacks.

Topics: Aged; Aged, 80 and over; Animals; Blotting, Western; Cadaver; Coloring Agents; Female; Fluorescein-5-isothiocyanate; Fluorescent Dyes; Ganglia, Parasympathetic; Glial Fibrillary Acidic Protein; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Male; Neurons; Nitric Oxide Synthase; Pituitary Adenylate Cyclase-Activating Polypeptide; Rats; Rats, Sprague-Dawley; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; Receptors, Vasoactive Intestinal Peptide; Rhodamines; Species Specificity; Vasoactive Intestinal Peptide

In contrast to research findings describing the localization of nitric oxide synthases (NOS), guanylyl cyclases, and cyclic adenosine monophosphate (cAMP)- and cyclic guanosine monophosphate (cGMP)-degrading phosphodiesterase isoenzymes in the human vagina, the distribution of proteins known as major targets for cyclic nucleotides has not yet been evaluated. cAMP- and cGMP-dependent protein kinases (cAK, cGKI) have been identified as important receptors for cyclic nucleotides downstream the signaling cascades.. To investigate, by means of immunohistochemistry, the expression of cAK and cGKI in relation to endothelial NOS (eNOS), vasoactive intestinal polypeptide (VIP), and protein gene product 9.5 (PGP 9.5) in the human vagina.. Expression and distribution of cAK and cGKI(alpha,beta) in relation to eNOS, VIP, and PGP 9.5 in human vaginal tissue.. Immunohistochemical techniques were applied to sections of human vaginal full wall specimens in order to evaluate the presence of cAK and cGKI(alpha,beta) in relation to VIP, PGP 9.5, and eNOS, respectively. Western blot analyses were conducted using cytosolic supernatants of homogenized specimens of the vaginal wall and epithelium.. Immunostaining specific for cGKIbeta was observed in vascular and nonvascular smooth muscle of the vagina. In the endothelial layer, cGKIbeta was found colocalized with eNOS. In contrast, no signals indicating cGKIalpha were registered. cAK-positive subepithelial vessels were found to be innervated by a dense meshwork of PGP-containing varicose nerve fibers, some of which presented expression of VIP. The expression of cAK and cGKIbeta was confirmed by Western blotting.. Our results demonstrate the expression of cAK and cGKIbeta in the human vagina. The colocalization with VIP and eNOS underlines the significance of both the cAMP and GMP pathway in the control of human vaginal vascular and nonvascular smooth muscle.

Topics: Adolescent; Adult; Blotting, Western; Cadaver; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Cyclic GMP; Cyclic GMP-Dependent Protein Kinases; Endothelium; Female; Frozen Sections; Gene Expression Regulation, Enzymologic; Humans; Immunohistochemistry; Nitric Oxide Synthase Type III; Sexuality; Signal Transduction; Ubiquitin Thiolesterase; Vagina; Vasoactive Intestinal Peptide; Young Adult

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

In an earlier study we found more than twice as many vasopressin (AVP) neurons in the suprachiasmatic nucleus (SCN) of homosexual men as compared to heterosexual men. The present measurements in the same individuals showed that there is no difference in the number of vasoactive intestinal polypeptide (VIP)-expressing neurons in the SCN. The reduced nuclear diameter of both VIP and AVP neurons in the SCN as found in homosexual men points to metabolic alterations in the SCN in relation to sexual orientation.

Topics: Adult; Arginine Vasopressin; Cadaver; Cell Count; Homosexuality, Male; Humans; Male; Neurons; Sexual Behavior; Suprachiasmatic Nucleus; Vasoactive Intestinal Peptide; Vasopressins