vasoactive-intestinal-peptide and Pruritus

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.

Topics: Amino Acid Sequence; Animals; Calcitonin Gene-Related Peptide; Edema; Erythema; Histamine Release; Humans; Mast Cells; Molecular Sequence Data; Neurons, Afferent; Pruritus; Receptors, Tachykinin; Skin; Skin Diseases; Tachykinins; Vasoactive Intestinal Peptide

Responses to acetylcholine (ACh) and vasoactive intestinal polypeptide (VIP) were investigated in atopic eczema (AE) patients. To elucidate the involvement of histamine to ACh-provoked vasoreactions and sensations, we applied a selective H1-antagonist (cetirizine) 3 h prior to the ACh-administration. Solutions of acetylcholine (ACh, 0.55 M) and vasoactive intestinal polypeptide (VIP, 1.5x 10(-5) M) were injected (10 microl) intracutaneously into the volar forearm of 14 healthy subjects and 14 atopic eczema (AE) patients. The substances were applied as single stimulus as well as in combination. Sensations evoked by the stimulation were recorded using 2 visual analog scales (VAS). Vasoreactions were analyzed with the new technique of computer assisted video image analysis. With this method we measured the dynamics of the flare development and the extension of the final flare size independent of the observer's assessment. In control subjects the development and extension of the final flare size was almost similar, regardless whether ACh and VIP were applied in combination or separately. Compared to healthy controls, after injection of ACh, VIP and the combination of VIP and ACh smaller flare sizes were recorded in AE patients. After VIP was given, the control subjects reported pruritus, which was significantly augmented compared to AE patients. In contrast, controls reported a burning pain after the injection of ACh, whereas AE patients felt predominantly pruritus. Itch sensation after the combined application of VIP and ACh was significantly elevated in AE patients. Consequently, we assume that mediators of sudomotor neurons, i.e., VIP and ACh meet in AE patients apparently sensitized nociceptive primary afferents and induce exaggerated itch, pain and flare responses. When pretreated with the selective H1-antagonist cetirizine before ACh was injected, pain and erythema due to ACh was diminished in healthy controls. In contrast, cetirizine did not influence the size of erythema and the magnitude of sensation in AE patients. We conclude, that the release of histamine is not involved in ACh-induced erythema and pruritus in AE. These data provide evidence that pruritus can be elicited in atopic eczema by a cholinergic, histamine independent mechanism.

Topics: Acetylcholine; Adult; Cetirizine; Cholinergic Agents; Cross-Over Studies; Dermatitis, Atopic; Double-Blind Method; Erythema; Female; Histamine H1 Antagonists; Humans; Injections, Intradermal; Male; Pain; Pruritus; Psychophysics; Skin; Vasoactive Intestinal Peptide

We analysed vasoreactions and sensations of atopic eczema (AE) patients and healthy controls after intracutaneous (i.c.) injection of vasoactive intestinal polypeptide (VIP) and acetylcholine (ACh). Blood flow was measured by laser Doppler flowmetry (LDF). Plasma extravasation and flare size were evaluated planimetrically, and sensations were recorded using visual analog scales. Three groups of subjects (controls, AE patients suffering from acute eczema and AE patients during a symptom-free period) were investigated. We administered VIP separately at concentrations of 1.5 x 10(-7), 1.5 x 10(-6) and 1.5 x 10(-5) M and in combination with ACh (5.5 x 10(-6) M) into the volar forearm of the subjects. Both substances led to an increase in LDF measurements and induced a wheal and flare reaction. Blood flow was elevated as a function of dose after a single VIP application in all groups. Compared with healthy controls, a significant increase in blood flow was measured after combined VIP and ACh administration in AE patients suffering from acute AE, whereas flare area and plasma extravasation were significantly reduced after single VIP and combined VIP and ACh injections, respectively. In all groups, VIP induced dose-dependent pruritus. Compared with a control stimulus (0.9% sodium chloride and ACh), combined injections of VIP and ACh had no additional effect on the magnitude of the sensation. In AE patients, the intensity was similar to that experienced by the control subjects, but the quality of sensation was different: ACh induced pain in the control subjects, pruritus in AE patients, and a mixture of pain and itching in AE patients showing no symptoms. Our results suggest that VIP- and ACh-induced skin reactions and the quality of the sensations depend on the activity of the atopic eczema. Confirming our former studies, AE patients develop a different quality of sensation after ACh administration and also after administration of VIP combined with ACh. Therefore, we suggest that ACh might be involved in the pathomechanisms of pruritus in AE.

Topics: Acetylcholine; Adult; Dermatitis, Atopic; Dose-Response Relationship, Drug; Drug Combinations; Drug Synergism; Female; Humans; Hypersensitivity; Injections, Intradermal; Laser-Doppler Flowmetry; Male; Pruritus; Regional Blood Flow; Severity of Illness Index; Skin; Skin Diseases; Skin Tests; Vasoactive Intestinal Peptide

Although itch is the predominant symptom of atopic dermatitis (AD), it is poorly characterized and subjective. The objective assessment of itch intensity is important for treatment and follow-up in patients with AD.. To determine what objective clinical parameter(s) could be used as biomarker(s) for itch intensity in patients with AD.. This is a retrospective and cross-sectional study. Seventy-five patients, aged 7 months-49 years with equal sex ratio, were enrolled in 2000 according to criteria proposed by Hanifin and Rajka. Thirty-five age- and sex-matched subjects who visited the dermatological clinic but were otherwise healthy served as controls. Subjective itch intensity was divided into four grades of severity. Disease severity was measured by SCORAD index, which also includes itch intensity as part of the measurement. Transepidermal water loss (TEWL) and skin surface pH were measured by noninvasive methods in clinically normal skin on the forearm. Serum beta-endorphin and vasoactive intestinal peptide (VIP) were determined by radioimmunoassay. Ordinal logistic regression was used to assess the trend of the subjective itch intensity and SCORAD index by serum IgE, beta-endorphin, VIP, TEWL and skin pH.. There were significant trends for itch intensity with IgE, beta-endorphin and TEWL. After adjustment for sex, age and other variables, the odds ratio (OR) for itch intensity by log IgE, beta-endorphin and TEWL was 2.103 [95% confidence interval (CI) 1.222-3.618], 1.100 (95% CI 1.005-1.203) and 1.081 (95% CI 1.009-1.158), respectively. The OR for disease severity by log IgE, beta-endorphin and TEWL was 2.250 (95% CI 1.149-4.407), 1.156 (95% CI 1.086-1.231) and 1.071 (95% CI 0.971-1.182), respectively. In contrast, there was no association between serum VIP concentration and itch intensity.. Beta-endorphin and IgE are both useful biomarkers for itch and disease severity in patients with AD, while TEWL is a good biomarker for itch intensity. These biomarkers provide a way to assess the itch intensity in patients with AD.

Topics: Adolescent; Adult; beta-Endorphin; Biomarkers; Child; Child, Preschool; Dermatitis, Atopic; Epidemiologic Methods; Female; Humans; Hydrogen-Ion Concentration; Immunoglobulin E; Infant; Male; Middle Aged; Pruritus; Severity of Illness Index; Vasoactive Intestinal Peptide; Water Loss, Insensible

Aquadynia (water-related cutaneous pain) is a very rare disorder, recently described.. A 40 year-old woman suffered from aquagenic pruritus, complicated by paresthesia and pain. There was no clinical argument in favor of a psychiatric disorder, Fabry's disease or any other disease. Clinical and histological cutaneous examinations were normal. Immunohistochemical study of neurotransmitters (substance P, calcitonin gene-related peptide or CGRP, vasoactive intestinal peptide or VIP, somatostatine) did not show any modification in nerve density. However, VIP-immunoreactive epidermal cells were observed. Electromyography and study of somesthesic-evoked potentials were normal. No treatment had provided any efficacy. Clonidine and capsaicin had been prescribed with partial success.. Three other cases of aquadynia have been reported. Differential diagnoses of aquadynia are aquagenic pruritus and urticaria, hysteria or simulation, Fabry's disease, erythermalgia, peripheral neuropathy or polycythemia vera. The presence of VIP-immunoreactive cells suggests that VIP could be produced by these cells after contact with water. The effects of propanolol and clonidine on aquadynia are in favor of an adrenal component.

Topics: Adult; Electromyography; Female; Humans; Pain; Paresthesia; Pruritus; Vasoactive Intestinal Peptide; Water

Notalgia paresthetica (NP) is a sensory neuropathy the pathogenesis of which is not yet completely elucidated.. The aim of this study was to investigate the histopathological changes in NP with special emphasis on cutaneous innervation.. Along with site-matched biopsies from 5 healthy individuals, lesional skin biopsies from 14 cases of NP and biopsies from contralateral nonlesional skin in 9 of these cases were stained with hematoxylin-eosin and Congo red. For immunohistochemical analysis, all samples were stained with two general neural markers (S-100 protein and protein gene product 9.5) and two neuropeptides (vasoactive intestinal polypeptide and substance P).. Light microscopy was compatible with postinflammatory hyperpigmentation. Immunohistochemistry did not reveal a significant difference in the staining pattern of lesional skin and control tissue (p > 0.05). Although not reaching statistical significance, the percentage of cases which showed no staining was higher in the group of patients with more chronic NP.. The finding of less immunohistochemical staining in cases with more chronicity could be of clinical importance and is worth investigating further.

Topics: Adult; Aged; Back Pain; Biomarkers; Epidermis; Female; Humans; Hyperpigmentation; Immunohistochemistry; Male; Middle Aged; Polyradiculoneuropathy; Pruritus; S100 Proteins; Substance P; Thiolester Hydrolases; Ubiquitin Thiolesterase; Vasoactive Intestinal Peptide

Low-frequency (2 Hz) transcutaneous electrical nerve stimulation (TNS) may produce prolonged and widespread sympatho-inhibition resulting in improved skin microcirculation with increased skin temperature in patients with peripheral vascular insufficiency. The method has previously been used successfully to improve peripheral circulation in such patients and to accelerate healing of chronic skin ulcers of various etiology. The present report deals with healing of atopic eczema and relief of pruritus by low-frequency TNS treatment in a patient who was followed for 2 years, the first 8 months with daily recordings of the effects, and then for an additional 16 months during which period TNS only occasionally was used. TNS also produced increased plasma levels of ACTH, cortisol and vasoactive intestinal polypeptides (VIP). The mechanisms of the favourable clinical effects are discussed.

Topics: Adolescent; Adrenocorticotropic Hormone; Dermatitis, Atopic; Electric Stimulation Therapy; Female; Humans; Hydrocortisone; Pruritus; Skin Temperature; Transcutaneous Electric Nerve Stimulation; Vasoactive Intestinal Peptide

Topics: Animals; Arteries; Cats; Dermatitis; Dogs; Gastrointestinal Hormones; Guinea Pigs; Haplorhini; Humans; Nerve Fibers; Neurotensin; Nociceptors; Pruritus; Rats; Skin; Substance P; Vasoactive Intestinal Peptide; Veins

The effect of various opioid or putative neurotransmitter peptides on histamine-induced itch and flare responses was studied in humans after intradermal injection. Significant enhancement of the histamine responses was induced by the stable methionine-enkephalin analogue FK 33-824, beta-endorphin and morphine. The putative neurotransmitters substance P and vasoactive intestinal polypeptide (VIP)--which moreover are potent histamine liberators--had no enhancing effect. The potentiation induced by FK 33-824 was induced neither by local pretreatment with Compound 48/80 to deplete the local stores of mast-cell-bound histamine, nor by oral pretreatment with indomethacin to inhibit prostaglandin formation in the skin. Thus, the enhancement did not seem to be due to histamine release or to prostaglandin formation and the mechanism of the effect remains to be shown. The specific morphine antagonist naloxone did not inhibit the potentiation by FK 33-824, which might indicate that ordinary opiate receptors were not involved. The results support the idea that pain and itch are qualitatively separate processes and suggest possible mechanisms of morphine-induced pruritus. The findings are of particular interest in view of recent reports on the presence of methionine-enkephalin in Merkel cells.

Topics: Adolescent; Adult; beta-Endorphin; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Dinoprostone; Drug Synergism; Endorphins; Enkephalin, Methionine; Female; Histamine; Humans; Indomethacin; Male; Middle Aged; Morphine; Naloxone; Prostaglandins E; Pruritus; Skin; Substance P; Vasoactive Intestinal Peptide

Pruritus, whealing and axon-reflex erythema appeared in human skin after intradermal injection of (i) several peptides with a putative transmitter function, i.e. vasoactive intestinal polypeptide (VIP) (10(-7)--10(-4) M), [Gln4]-neurotensin (10(-7)--10(-4) M), neurotensin (10(-5)--10(-4) M) and secretin (10(-5)--10(-4) M), which were compared with substance P (10(-7)--10(-5) M) previously shown to be one of the most potent histamine liberators when administered intradermally in humans; (ii) the basic polypeptide protamine (10(-7)--10(-4) M); and (iii) histamine (0.3-10 micrograms/ml) and the histamine liberator compound 48/80 (0.3-10 micrograms/ml). The reactions were inhibited in a dose-related manner by the antihistamine mepyramine, indicating that the peptide-induced responses were mediated by released histamine. This was further confirmed by the histamine release observed when the peptides were incubated with rat peritoneal mast cells. In human skin, VIP was more potent than the other neuropeptides and had roughly the same potency as substance P. The two adjacent basic amino-acid residues and the amide substitution of the terminal C-group of VIP, in addition to its strong net basic charge, may explain its potency as a histamine releaser.

Topics: Adolescent; Adult; Animals; Female; Histamine Release; Humans; Injections, Intradermal; Male; Mast Cells; Middle Aged; Neurotensin; Neurotransmitter Agents; Pruritus; Rats; Secretin; Skin; Vasoactive Intestinal Peptide