vasoactive-intestinal-peptide and Peripheral-Nervous-System-Diseases

Nerves have been identified in bone. Their function has recently become the focus of intense study. Metabolic control of bone is influenced by the nervous system. Potential transmitters of this influence include glutamate, calcitonin gene-related protein (CGRP), substance P, vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating polypeptide (PACAP), leptin, and catecholamines. Disorders of nerves - central or peripheral--can have substantial influence on bone health and repair. Specifically considered are the potential neural influences at work in such conditions as osteoporosis, fracture healing, Charcot osteoarthropathy, musculoskeletal pain syndromes, heterotopic ossification, skeletal growth and development, and obesity-related increased bone density. In this article, we review the current state of experimental and clinical evidence implicating the role of nervous tissue in regulating bone biology and discuss the current understanding of molecular signaling between nervous and osseus tissue in the homeostatic maintenance of the skeleton.

Topics: Arthropathy, Neurogenic; Bone and Bones; Brain; Calcitonin Gene-Related Peptide; Catecholamines; Central Nervous System Diseases; Denervation; Glutamic Acid; Humans; Neuropeptides; Peripheral Nervous System Diseases; Substance P; Vasoactive Intestinal Peptide

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS Dementia Complex; Amino Acid Sequence; Animals; Calcinosis; CD4 Antigens; CD4-Positive T-Lymphocytes; Cell Survival; Central Nervous System; Child; Child Behavior Disorders; Child, Preschool; Cognition Disorders; Eye Diseases; Female; Global Health; Hippocampus; HIV; HIV Antibodies; HIV Envelope Protein gp120; Humans; Infant; Infant, Newborn; Male; Mice; Molecular Sequence Data; Molecular Structure; Neurons; Peptide T; Peripheral Nervous System Diseases; Receptors, Virus; Severity of Illness Index; Spinal Cord Diseases; Tomography, X-Ray Computed; Vacuoles; Vasoactive Intestinal Peptide

The spontaneous autoimmune peripheral polyneuropathy (SAPP) model in B7-2 knockout nonobese diabetic mice mimics a progressive and unremitting course of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). In this study, bone marrow-derived dendritic cells (DCs) were transduced to express vasoactive intestinal polypeptide (VIP) using a lentiviral vector (LV-VIP). These transduced DCs (LV-VIP-DCs) were then injected intravenously (i.v.) into 16-week-old (before disease onset) and 21-week-old (after disease onset) SAPP mice in order to prevent or attenuate the disease. Outcome measures included behavioral tests, clinical and histological scoring, electrophysiology, real-time PCR, flow cytometry analyses, and enzyme-linked immunosorbent assay. LV-VIP-DCs were recruited to the inflamed sciatic nerve and reduced the expression of inflammatory cytokines. A single injection of LV-VIP-DC delayed the onset of disease, stabilized, and attenuated clinical signs correlating with ameliorated behavioral functions, reduced nerve demyelination, and improved nerve conduction. This proof-of-principle study is an important step potentially leading to a clinical translational study using DCs expressing VIP in cases of CIDP refractory to standard immunosuppressive therapy.

Topics: Animals; Cells, Cultured; Dendritic Cells; Male; Mice; Peripheral Nervous System Diseases; Polyneuropathies; Vasoactive Intestinal Peptide

Gabapentin has been used effectively for neuropathic pain with mild side effects. Two cases of gabapentin-induced sexual dysfunction are reported and discussed.

Topics: Adolescent; Amines; Analgesics; Cyclohexanecarboxylic Acids; Female; Gabapentin; gamma-Aminobutyric Acid; Humans; Libido; Male; Middle Aged; Neuralgia; Nitric Oxide; Peripheral Nerves; Peripheral Nervous System Diseases; Sexual Dysfunction, Physiological; Sexual Dysfunctions, Psychological; Up-Regulation; Vasoactive Intestinal Peptide; Weight Gain; Withholding Treatment

Diminished healing in neuropathic tissues suggests an important regulatory role for peripheral neurogenic factors in connective tissue healing. Although neurogenic factors, including neuropeptides, can induce cell proliferation and influence inflammatory cell chemotaxis in vitro, there is little appreciation of the potential of neuropeptides to affect connective tissue healing in vivo. We created both efferent and afferent peripheral neuropathies in 55 female Wistar rats. First, we showed that neuropathy led to impaired healing of ruptured ligaments. We then showed that local delivery of specific neuropeptides could reverse the functional deficits of these neuropathic ligaments in only 2 weeks. In substance P and vasoactive intestinal peptide-treated medial collateral ligaments (MCLs), the mechanical properties of these healing neuropathic tissues returned to values at or above normally innervated, intact ligaments. In addition, neuropeptide Y stimulated MCL healing in this model. These findings suggest a new paradigm to improve neuropathic soft connective tissue healing.

Topics: Animals; Calcitonin Gene-Related Peptide; Disease Models, Animal; Female; Femoral Nerve; Ligaments; Neuropeptide Y; Neuropeptides; Peripheral Nervous System Diseases; Rats; Rats, Wistar; Rupture; Substance P; Sympathectomy; Vasoactive Intestinal Peptide; Wound Healing

To test the hypothesis that genital prolapse may be related to peripheral nerve abnormalities, we examined the changes occurring to peptide-containing nerve processes supplying the periurethral muscles in women with stress urinary incontinence associated with prolapse.. Thirty patients with genital prolapse and 10 age-matched control subjects entered the study. All patients were evaluated by urodynamic investigations. Ten of 30 patients had pure stress urinary incontinence; none of the control subjects was incontinent. During surgery, four biopsy samples were obtained from each woman from the periurethral and perirectal muscles. The muscle sections were processed for immunohistochemistry using specific antibodies to glial (S-100 protein) and general neuronal markers (neuron-specific enolase) and neuropeptides, including neuropeptide Y, vasoactive intestinal polypeptide, and substance P. The evaluation of immunolabeled nerves was based on a semiquantitative analysis that allowed for a four-point ordinate scale score.. S-100 and neuron-specific enolase immunoreactive nerve fibers, running either singly or in small bundles, along with a dense network of neural processes containing neuropeptide Y, vasoactive intestinal polypeptide, and substance P, were found throughout the connective tissue and striated muscle of the control specimens. In contrast, in the muscle specimens from those with genitourinary prolapse, both the density and the intensity of neuropeptide Y, vasoactive intestinal polypeptide, and substance P immunoreactive nerves were markedly reduced compared with the control specimens.. The evidence of a reduced peptide-containing nerve supply to the perineal muscles provides a morphologic basis suggesting that neural abnormalities contribute to the pathogenesis of genital prolapse and urinary incontinence.

Topics: Aged; Biomarkers; Biopsy; Birth Weight; Connective Tissue; Denervation; Female; Humans; Middle Aged; Models, Neurological; Muscle, Skeletal; Nerve Tissue Proteins; Neurons; Neuropeptide Y; Neuropeptides; Obesity; Parity; Pelvic Floor; Peripheral Nervous System Diseases; Phosphopyruvate Hydratase; Postmenopause; Rectum; S100 Proteins; Substance P; Urethra; Urinary Incontinence, Stress; Uterine Prolapse; Vasoactive Intestinal Peptide

A predominance of sensory neuropathy was earlier described in Sjögren's syndrome (SS), which might precede the presence of sicca symptoms. The mechanism of sensory neuropathy in SS is unknown. Therefore, the aim of this study was to determine the quantitative changes of the different neuropeptide containing nerve terminals and the immunocompetent cells in labial salivary glands of primary SS.. Immunohisto- and immunocytochemical methods were used for the detection of immunoreactive (IR) elements and the data were compared with the healthy controls.. All of the investigated IR nerve fibres were found in different quantity and localisation in both of control and SS glands. The density of them was changed variously in SS. The number of the substance P (SP), neuropeptide Y (NPY) (P < 0.05), galanin (GAL) IR nerve terminals was decreased, however, the number of vasoactive intestinal polypeptide (VIP) and tyrosine beta-hydroxylase (TH) IR nerve fibres (P < 0.05) was increased compared to the control. There were no IR immunocompetent cells in the control materials, however, a large number of them showed IR for SP (46.2%) and NPY (34.4%) in the SS. The IR was demonstrated mainly in the mast cells, plasma cells and some of the lymphocytes.. These neuropeptides might have a role in the sensory neuropathy; they might activate nociceptive and sympathetic pathways. Some neuropeptides (SP, NPY) are endogenous in the immune system and produced in certain conditions, e.g. inflammation and chronic autoimmune disorders such as SS, so they might participate in the neuroimmunomodulation and contribute to the atrophy, apoptosis and necrosis.

Topics: Adult; Aged; Female; Galanin; Humans; Lymphocytes; Male; Mast Cells; Microscopy, Electron; Middle Aged; Nerve Fibers; Neuroimmunomodulation; Neuropeptide Y; Neuroprotective Agents; Peripheral Nervous System Diseases; Plasma Cells; Salivary Glands, Minor; Sjogren's Syndrome; Substance P; Tyrosine 3-Monooxygenase; Vasoactive Intestinal Peptide

Colonic strictures are rare in patients who have cystic fibrosis, but recently have developed in those who have been treated with delayed-release high-dose pancreatic enzyme supplements. Colonic strictures from eight such pediatric patients showed neural abnormalities consisting of ganglion cell hyperplasia and ectopia, and intermyenteric plexus hyperplasia. Cholinergic and adrenergic stains of mucosal nerve fibers were more prominent in histological sections of the cystic fibrosis strictures than in sections from colons of children without cystic fibrosis. The mean grade of staining with acetylcholinesterase in the lamina propria of the strictured cystic fibrosis colons was 2.38 +/- 1.25, compared with .93 +/- .93 (P < .055) in bowels from children without cystic fibrosis. The mean grade for tyrosine hydroxylase staining in the lamina propria was 2 +/- .97 in the strictures and was .79 +/- .81 (P < .05) in the bowels of children who did not have cystic fibrosis. Vasoactive intestinal peptide staining in bowels from children with cystic fibrosis with and without stricture did not differ significantly from that of children without cystic fibrosis. Vasculopathy consisting of fibrointimal hyperplasia in submucosal veins and mesenteric arteries was found only in colonic strictures owing to cystic fibrosis. Colonic strictures in patients with cystic fibrosis who received high-dose pancreatic enzyme supplements contain ganglion cell abnormalities, and mucosal cholinergic and adrenergic activity may be increased in these strictures. The stricture vasculopathy may be drug-related and/or related to increased catecholamine activity.

Topics: Acetylcholinesterase; Adolescent; Adrenergic Fibers; Catecholamines; Child; Child, Preschool; Cholinergic Fibers; Choristoma; Colon; Colonic Diseases; Constriction, Pathologic; Cystic Fibrosis; Female; Ganglia; Humans; Hyperplasia; Infant, Newborn; Intestinal Mucosa; Male; Mesenteric Arteries; Pancreas; Pancreatic Extracts; Peripheral Nervous System Diseases; Tunica Intima; Tyrosine 3-Monooxygenase; Vascular Diseases; Vasoactive Intestinal Peptide

Vasoactive intestinal polypeptide (VIP) and substance P (SP) immunoreactivity are reduced in the cutaneous nerves of diabetic patients with peripheral neuropathy. The functional significance of this finding was studied by measuring the forearm sweat response to intradermal methacholine and the effect of coadministration of VIP and SP in six normal subjects, and in six diabetic patients with neuropathy and eight without. Flare responses to the two peptides were also measured. Methacholine-induced sweat output was significantly greater in neuropathic patients compared with the other groups (p < 0.05), suggesting upper limb denervation supersensitivity. VIP and SP alone did not evoke sweating in any subject. Injection of VIP or SP reduced methacholine-induced sweating to a similar degree in all groups, except that the reduction was smaller in the non-neuropathic group than in the others (p = 0.028 versus normal subjects, p = 0.014 versus neuropathic diabetic patients). Flare responses to the peptides were markedly reduced in the neuropathic patients compared with the other groups (p < 0.01). In neuropathic patients, increased sweat responses and decreased flare coexist with diminished neurophysiological measurements; cutaneous sweating and flare responses provide valuable additional information to conventional methods of neurological assessment in diabetic neuropathy.

Topics: Adult; Blood Vessels; Diabetic Neuropathies; Humans; Male; Methacholine Chloride; Middle Aged; Peripheral Nervous System Diseases; Substance P; Sweating; Vasoactive Intestinal Peptide

A series of experiments were designed to develop and validate an animal model of lumbar radiculopathy. More specifically, these investigations introduced a model of chronic neuropathic pain in the rat associated with clinically relevant lumbar nerve root trauma and evaluated the ability of the model to effect symptoms and begin to understand the underlying neurochemical and neurophysiologic factors associated with these neurologic abnormalities.. A search of the literature suggested that these studies were a first attempt to distinguish and elucidate an experimental lumbar radiculopathy.. Two basic approaches to nerve trauma were considered, direct damage to the nerve via compression, and introduction of foreign materials in proximity to the nerve root that might cause irritation and inflammation leading to chronic symptoms. Ligature around the nerve (i.e., surrounding the nerve with a suture) was considered a plausible irritant that might behave in an animal model in a similar way that nerve root entrapment, often observed in HNP and stenosis cases, might function in humans. Further, varying levels of irritation was modeled by using 4-0 silk as a mild and 4-0 chromic gut as a more harsh irritant.. Five distinct treatments of the nerve roots were investigated initially: 1) a sham intervention, where the surgery simply exposed the nerve roots and dorsal root ganglion followed by standard closing procedures; 2) nerve root clipping, where the nerve roots were clipped with a microhemoclip; 3) 4-0 silk ligature, where two loose ligatures of 4-0 silk were placed around the nerve roots; 4) 4-0 chromic gut 1, where one loose ligature of 4-0 chromic gut was placed around the nerve roots; and 5) 4-0 chromic gut 2, where four 0.3 cm pieces of 4-0 chromic gut were laid adjacent to the nerve roots and secured by two loose ligatures of 4-0 chromic gut. ANOVA techniques were used to test for differential effects across time for the five treatment groups in terms of animal function and biochemistry in the DRG.. Rats treated with chromic gut ligature in large quantity demonstrated differential patterns of results on the injured and noninjured sides consistent with a lumbar radiculopathy. The injured side demonstrated significantly worse thermal hyperalgesia related to neuropathic pain (P < 0.0001); initial mechanical hypoalgesia (P < .001), and motor dysfunction (P < .001) resolving within 2 weeks; significantly increased c-fos counts (P < .0001) 2 weeks postoperatively, which showed a consistent trend toward baseline and return to baseline by 12 weeks; significantly greater and highly increased VIP concentrations in the dorsal root ganglia 2 weeks postoperatively (P < .0001) that did not resolve or tend towards baseline after 12 weeks of follow-up in conjunction with a trend toward VIP depletion in the spinal cord 2 weeks postoperatively that did resolve to baseline until a 12-week concentration indicated a significant increase in concentration (P < .002). Quantitative and qualitative changes in c-fos and VIP, correlated with the patterns of behavior and function. Thus, for the first time, evidence to link outcome behaviors and function with underlying neurochemical processes is suggested.. When the same apparent conditions can be demonstrated in some situations to be causing pain and in other situations to be independent of pain, some additional factor or factors not considered in the original investigations may be mediating the outcome. Neurochemical consequences of nerve root irritation provide a theoretical framework for hypothesizing about various types of mediating events that might explain how similar apparent pathology might reasonably lead to different predictions about behavior consequences of the pathology.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Animals; Calcitonin Gene-Related Peptide; Ganglia, Spinal; Genes, fos; Hot Temperature; Male; Nerve Compression Syndromes; Pain; Pain Threshold; Paralysis; Peripheral Nervous System Diseases; Rats; Rats, Sprague-Dawley; Spinal Cord; Spinal Nerve Roots; Substance P; Sutures; Vasoactive Intestinal Peptide