Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurokinins are a family of peptides which are released from sensory nerves. This family involves substance P, neurokinin A and B which stimulate neurokinin-NK1, -NK2 and -NK3 receptors respectively. The neurokinins as well as C.G.R.P. (calcitonin gene related peptide) and V.I.P. (vasoactive intestinal peptide) are the mediators of the non adrenergic non cholinergic (N.A.N.C.) nervous system. All these peptides can be released by nerve fibres innervating the skin. They are mainly inflammatory mediators. At skin level, the neurokinin induce itch, wheal and flare. Itch and flare are partly due to histamine release from mast cells in response to substance P.
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PMID:[Neurokinins and the skin]. 769 70

Systemic sclerosis is characterized by vascular dysfunction. Itch is sometimes present in early stages of the disease. This prompted us to study the innervation of the skin by immunocytochemistry. Antibodies to neuropeptide Y and vasoactive intestinal peptide were used for autonomic nerves. Sensory innervation was studied using antibodies to substance P and calcitonin gene-related peptide. Protein gene product 9.5 was used as a general neuronal marker. Skin biopsies from affected (lower arm) and non-affected (upper back) sites on 10 patients with systemic sclerosis and from corresponding sites on 10 sex- and age-matched healthy controls were studied. Regional variations were found in the occurrence of peptidergic nerve fibers. In the patients the density of nerve fibers (measured semiquantitatively) stained by the panneuronal marker was lower in affected than in unaffected skin (p < 0.05). There were no significant differences in peptidergic innervation between patients and controls. However, there was a tendency to higher density of neuropeptide Y-positive nerve fibers in the forearm skin in 6 to 10 patients, as compared to only 1 of 10 healthy controls.
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PMID:Occurrence and distribution of peptidergic nerve fibers in skin biopsies from patients with systemic sclerosis. 874 Feb 66

Forty postmenopausal women with bone mineral density (BMD) > 2 standard deviations below the mean value for healthy age matched controls were enrolled into an open controlled study to evaluate the metabolic and bone effects of ipriflavone (IP) versus salmon calcitonin (sCT) over a 12 month period. Both treatments significantly increased BMD after 6 and 12 months. A 4.3% increase of BMD was obtained in the IP treated group and a 1.9% in the sCT treated group after 12 months (p < 0.001 between treatments). Bone metabolism markers (serum osteocalcin, alkaline phosphatase, urinary calcium and hydroxyproline/creatinine ratio) were significantly reduced in both groups (p < 0.001). The reduction of urinary hydroxyproline/creatinine ratio was significantly greater (p < 0.05) in the IP group after 12 months. Both treatments were well tolerated. Four patients in the IP group reported gastralgia while two patients in the sCT group reported pruritus and one patient epistaxis.
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PMID:Metabolic and bone effects after administration of ipriflavone and salmon calcitonin in postmenopausal osteoporosis. 874 73

There is increasing evidence that neuropeptides may be involved in the pathogenesis of atopic dermatitis (AD). This study examines whether neuropeptide distribution in the skin of patients with AD differs from normal controls. The distribution and density of several neuropeptides were examined in lesional and non-lesional skin of AD patients (n = 5) and in normal controls (n = 4) using indirect immunofluorescence and image analysis. Cholinergic innervation was studied using cholinesterase histochemistry. Staining with the general neuronal marker protein gene product 9 x 5 showed a subepidermal network of nerves with fibres penetrating the epidermis, and nerves around blood vessels, sweat glands and hair follicles. Image analysis of nerves around sweat glands showed a significantly higher nerve density in non-lesional compared with both normal controls and lesional skin (P < 0.05); lesional compared with control skin showed no significant difference. In the epidermis the density of nerves was not significantly greater in non-lesional compared with lesional skin and controls. Calcitonin gene-related peptide immunoreactivity was similar in all subjects except in three of the AD patients, where more nerves appeared to penetrate the epidermis. Substance P immunoreactivity in the papillary dermis was seen in all AD patients but no controls. Vasoactive intestinal polypeptide and neuropeptide Y staining were similar in all groups. Acetylcholinesterase-positive nerves were found around sweat glands in all subjects, the staining being greatest in non-lesional and least in lesional skin. Occasional nerves were seen in the papillary dermis in lesional skin of two out of the four patients. We have demonstrated quantitative differences in nerve growth in clinically normal skin of AD patients, and altered cutaneous neuropeptide expression in these patients which may contribute to the pathogenesis of AD. The cause of atopic dermatitis (AD) has not been fully established but it is believed that there is a complex interaction between genetic susceptibility, precipitating environmental factors and disordered immune responsiveness. There is increasing evidence that neuropeptides may be involved in the pathogenesis of AD. Exacerbations of the disease can be provoked by stress, scratching and sweating which may be the result of neurogenic inflammation. One of the first features of an exacerbation is flushing of the affected skin and pruritus. Several neuropeptides that have been identified in human skin are potent inducers of vasodilation and may induce pruritus. Substance P (SP), calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) all cause vasodilation when injected intradermally, and SP and CGRP have been shown to be mediators of the weal and flare reaction. Spantide, a competitive antagonist of SP, has been shown to inhibit immediate and delayed-type hypersensitivity reactions. Part of these responses may be due to release of histamine and indeed elevated concentrations of histamine have been found in vivo in the skin and plasma of patients with AD. In this study the distribution and density of several neuropeptides were examined in lesional and nonlesional skin of AD patients and in normal controls using indirect immunofluorescence and image analysis. Cholinergic innervation was studied using cholinesterase histochemistry. Because many afferent fibres do not express CGRP or SP, the general neuronal marker protein gene product (PGP 9 x 5) was used to assess the overall nerve supply to the skin.
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PMID:Neuropeptides in the skin of patients with atopic dermatitis. 885 37

Neuropeptides (NP) are a heterogeneous group of proteins functioning as neurotransmitters, neuromodulators and neurohormones. More than fifty of these molecules have been described, and some have been detected in human skin through immunochemistry and radioimmunoassay. In this article we attempt to study the role played by some of these substances such as substance P (SP), calcitonin gene related peptide (CGRP), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), somatostatin (S), and neurotensin (N). Several NP induce inflammatory response with edema and erythema. They can also induce the release of histamine by mastocytes, regulate cutaneous blood flow, and participate in sweat regulation and nociception. They also exert their action over several cells that participate in immunity, acting as mitotic, and chemotactic factors, inhibiting or stimulating inflammatory mechanisms. Specific NP have their receptors on epidermal cells. We will also try to study certain diseases in which NP play an important role in inducing or alleviating lesions, such as psoriasis, atopic eczema, alopecia areata, vitiligo, nodular prurigo, aquagenic pruritus, hypertrophic scars and other entities.
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PMID:[Role of neuropeptides in dermatology]. 927 66

Upon activation nociceptors release neuropeptides in the skin provoking vasodilation and plasma protein extravasation in rodents, but only vasodilation in humans. Pivotal peptides in the induction of neurogenic inflammation comprise calcitonin gene-related peptide and substance P, the latter being suggested to act partly via degranulation of mast cells. In this study substance P and calcitonin gene-related peptide-induced vasodilation, protein extravasation, histamine release, and sensory effects were investigated simultaneously in human skin by dermal microdialysis. The vasodilatory prostaglandin E(2) and the mast cell activator codeine served as positive controls. Substance P and calcitonin gene-related peptide applied intradermally via large cut-off plasmapheresis capillaries induced dose-dependent local vasodilation, but only SP provoked protein extravasation in concentrations greater than 10(-9) M. Substance P-induced (10(-8)-10(-6) M) protein extravasation was not accompanied by histamine release and was unaffected by cetirizine (histamine H1 blocker, 200 microg per ml). Only the highest concentration of substance P (10(-5) M) induced significant histamine release. Neither neuropeptide caused any axon reflex erythema or any itch or pain sensation, whereas mast cell degranulation by codeine dose dependently provoked itch, flare, protein extravasation, and histamine release. In human skin calcitonin gene-related peptide and substance P induce vasodilation by a mechanism not involving histamine. No evidence for neuropeptide-induced activation of nociceptors was obtained. Our results suggest that endogenous calcitonin gene-related peptide and substance P have no acute sensory function in human skin. The lack of neurogenic protein extravasation in humans can most probably be attributed to low local concentrations of this neuropeptide still sufficient to exert trophic and immunomodulatory effects (10(-11) M), but too low to induce protein extravasation (10(-8) M) or even mast cell degranulation (10(-5) M). J Invest Dermatol 115:1015-1020 2000
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PMID:Acute effects of substance P and calcitonin gene-related peptide in human skin--a microdialysis study. 1112 Nov 35

Pharmacological studies have suggested that a subgroup of primary sensory neurons is responsive to histamine via the H1 receptor. However, which type of primary sensory neurons express H1 receptor is not known. We addressed this issue using in situ hybridization histochemistry with a cRNA probe for the guinea pig H1 receptor mRNA. H1 receptor mRNA was expressed in about 15-20% of the trigeminal and lumbar dorsal root ganglion (DRG) neurons, but none of the nodose ganglion neurons. The positive neurons in DRG were exclusively small in size and were labeled by isolectin B4, suggesting that these neurons have unmyelinated fibers. However, H1-receptor mRNA-expressing DRG neurons were not immunoreactive to substance P (SP) or calcitonin gene-related peptide (CGRP), which are implicated in the nociceptive transmission of the primary sensory system. Moreover, in guinea pigs neonatally treated with capsaicin (50 mg/kg), few CGRP-immunoreactive neurons were seen in DRG, but the percentage of H1-receptor mRNA-expressing neurons (15%-20%) and the intensity of the mRNA signals in these neurons were not affected by neonatal capsaicin treatment, suggesting that H1 receptor-expressing neurons are not sensitive to capsaicin. These findings suggest that H1-receptor-expressing neurons are involved in the transmission of a unique sensory modality such as itch. A marked increase in the number of mRNA-positive DRG neurons was observed 1-5 days after a crush injury of the sciatic nerve (3-4-fold of the control value). These neurons that turned mRNA-positive after the nerve crush were also mainly small-sized. The mRNA signals were detected in many peptidergic (SP/CGRP) neurons, in contrast to the normal condition. On the other hand, mRNA signals were decreased in the neurons that showed intense labeling in the normal condition. These results suggest that the gene expression of H1 receptors up-regulated in injured afferents may be involved in neuropathic pain.
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PMID:[Primary sensory neurons expressing histamine H1-receptor mRNA]. 1149 26

Stimulation of the nasal sensory nerves leads to sensations of pain and stuffiness. Type C nociceptive nerve releases neuropeptides including substance P and calcitonin gene related peptides that increase plasma extravasation and glandular secretion. This axonal response acts as an immediate protective mucosal defense mechanism. Recruited parasympathetic reflexes cause submucosal gland secretion via acetylcholine and muscarinic M(3) receptors. Itching, sneezing, and other avoidance behaviors rapidly clear the offending agents from the upper airways and protect the lower airways. Dysfunction of these nerves may contribute to allergic rhinitis, infectious rhinitis, nasal hyperresponsiveness, and possibly sinusitis. Sympathetic arterial vasoconstriction reduces mucosal blood flow, sinusoidal filling, and mucosal thickness, and so restores nasal patency. Loss of sympathetic tone may contribute to some chronic, nonallergic rhinopathies. Human axon responses differ from those in animals, an important distinction that limits extrapolation from other species.
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PMID:Upper airway neurogenic mechanisms. 1196 45

The cutaneous neurosensory system is suggested to be involved in the pathophysiology of pruritus and skin diseases such as psoriasis. We investigated if repeated subinflammatory doses of ultraviolet B (UVB) irradiation similar to those used to treat pruritus or psoriasis would affect the cutaneous neurosensory system. Sprague-Dawley rats were irradiated thrice weekly for 2-4 weeks with subinflammatory doses of UVB. Three days after the last UVB exposure: (i), the skin contents of substance P (SP), calcitonin gene-related peptide (CGRP), and nerve growth factor (NGF) were quantified; (ii), the skin nerve fiber density was observed; and (iii), the effect of UVB on mustard oil-induced neurogenic inflammation was determined. UV exposure significantly increased SP and CGRP content and mustard oil-induced neurogenic inflammation in UV-irradiated but not non-irradiated skin; however, it did not affect cutaneous NGF content or overall nerve fiber density. These data suggest that repeated subinflammatory UVB irradiation locally increases the content of cutaneous SP and CGRP by an increase of neuropeptide content of nerve fibers rather than by an increase of overall nerve fiber density.
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PMID:Repeated subinflammatory ultraviolet B irradiation increases substance P and calcitonin gene-related peptide content and augments mustard oil-induced neurogenic inflammation in the skin of rats. 1218 38

Opioid peptides are endogenous neuromodulators that play a major role in the nociceptive pathway by interacting with opioid receptors. So far, four opioid receptors (micro-, delta-, kappa-, orphan-receptor) have been cloned with a wide distribution in the central and peripheral nervous system. In the present study, we give first evidence for the presence of the micro-opioid receptor (MOR) isoform 1A in nerve fibers of human skin. Immunohistochemical analysis revealed MOR immunoreactivity to be present in dermal and epidermal nerve fibers. Double-immunofluorescence staining revealed that MOR is present on calcitonin gene-related protein (CGRP)-positive sensory nerve fibers, while autonomic nerves of blood vessels, hair follicles, or skin glands were negative. In diseased skin such as psoriasis vulgaris, atopic dermatitis, and prurigo nodularis, distribution of MOR 1A immunoreactivity was similar to that of normal skin. These findings expand our knowledge about a direct regulatory role of cutaneous opioid receptors in the skin. Thus, peripheral cutaneous opioid receptors may be involved in the transmission of pain and pruritus, respectively. This is supported by previous observation that opioid receptor antagonists may significantly diminish experimentally evoked histamine-induced itch of the skin. Together, our findings contribute to the understanding of the high antipruritic potency of opioid receptor antagonists in various skin and systemic diseases.
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PMID:Localization of mu-opioid receptor 1A on sensory nerve fibers in human skin. 1246 12


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