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)

To develop an allergic dermatitis model showing persistent scratching in mice, toluene-2,4-diisocyanate (TDI) was repeatedly painted onto the skin of hairless HR-1 mice, and induction of itch-associated scratching behavior was observed. When HR-1 mice were epicutaneously sensitized with 1% TDI and then challenged by repeated painting the cervicodorsal skin with 0.1% TDI once every 10 days until the 10th challenge, delayed type scratching responses peaked at 1 - 2 days after challenge. TDI at 0.1% hardly induced scratching in non-sensitized HR-1 mice. The delayed scratching response was influenced by neither an H(1) nor 5-HT(1/2) receptor antagonist. On the other hand, intradermal injection of histamine and serotonin induced frequent scratching in HR-1 mice. In conclusion, repeated application of TDI can induce delayed type allergic scratching. Although HR-1 mice are high responders to both histamine and serotonin, induction of the delayed response depends on neither of these chemical mediators. This delayed response may be useful in analyzing the mechanisms of allergic pruritus.
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PMID:Delayed type allergic itch-associated response induced by toluene-2,4-diisocyanate in hairless mice. 1450 Nov 51

Dry skin/barrier dysfunction is considered to be one of the characteristic features of atopic dermatitis (AD). When HR-1 hairless mice are fed a special diet, HR-AD, dry red skin is induced. We examined whether HR-AD-fed mouse could be used as a model for AD by showing itch-associated scratching behaviour and by analysing the immunological change. HR-1 mice were fed HR-AD from 4 weeks old. HR-AD-fed mice showed severe dry skin symptoms accompanied by a decrease in dermal water content and an increase in transepidermal water loss and prolonged scratching bout duration on day 14 or 28. These symptoms became gradually worse until day 56. Marked epidermal hyperplasia and slight increase in CD4+ cells in the skin were observed from day 28. In contrast, increases in circulating T cells and serum immunoglobulin E were seen from day 41. Other skin-infiltrating inflammatory cells, such as eosinophils and mast cells, were increased on day 56 but not on day 28. Though daily oral treatment with dexamethasone reduced the increased numbers of these cells, it did not affect the dry skin symptoms or the prolonged scratching episodes. In contrast, the development of dry skin was inhibited by feeding with 10% normal diet-containing HR-AD. The skin barrier dysfunction in HR-AD-fed mice is closely associated with the development of AD-like pruritus. Changes in the immunological parameters observed may be the consequence of skin barrier dysfunction. Our findings suggest that HR-AD-fed mouse could be used as a dry skin-based experimental model for AD.
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PMID:Atopic dermatitis-like pruritic skin inflammation caused by feeding a special diet to HR-1 hairless mice. 1588 82

To confirm the effectiveness of loratadine for relieving pruritus in atopic dermatitis, we examined the effect of this drug using animal models of atopic dermatitis associated pruritus in ICR and hairless mice. As for the results, in ICR mice, single oral administration of loratadine at a dose of 5 or 10 mg/kg significantly inhibited the dorsal scratching behavior induced by histamine or an antigen, and the effect of loratadine was more potent than that of fexofenadine and chlorpheniramine. In hairless mice, oral administration of loratadine at a dose of 10 mg/kg for 6 days significantly inhibited the facial scratching behavior induced by the feeding of a low magnesium diet. Furthermore, oral administration of loratadine at a dose of 10 mg/kg for 7 days also significantly inhibited the histamine-induced scratching behavior in the same animals. These results indicate that loratadine may be effective in preventing pruritus associated with atopic dermatitis.
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PMID:Effect of loratadine on mouse models of atopic dermatitis associated pruritus. 1591 37

HR-1 hairless mice fed with a special diet develop atopic-like dry skin, characterized by increased transepidermal water loss, and prolonged bouts of spontaneous scratching. In this study, the role of the skin barrier dysfunction in the prolongation of scratching was evaluated. Although the prolonged scratching was dose-dependently inhibited by opioid receptor antagonist naloxone, neither H(1) receptor antagonist, mepyramine, nor 5-HT(1/2) receptor antagonist, methysergide, affected it. Thus, the prolonged scratching could be itch-related response independent of histamine and serotonin. The application of petrolatum ointment on the skin temporarily alleviated the increase of transepidermal water loss for 60 min after treatment. Due to this alleviation in barrier dysfunction, the prolongation of scratching was significantly suppressed. However, when the barrier dysfunction relapsed, the scratching worsened. Taken together, a skin barrier dysfunction is associated with the itch-related response.
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PMID:Involvement of skin barrier dysfunction in itch-related scratching in special diet-fed hairless mice. 1635 56

The present study was performed to develop a new chronic itch model accompanied by skin lesions using hairless mice. The effects of some drugs on the itch response in this model were also studied. 2,4,6-Trinitrochlorobenzene (TNCB) was applied repeatedly on the rostral back of sensitized hairless mice every 2 days for 54 days, and the scratching behavior was observed on day 0, 18, 36 and 54. The skin symptoms and total IgE level were also observed. The number of scratches observed at 24 and 48 h after TNCB challenge was increased gradually from day 18 to day 54. An intimate relationship was observed between the number of scratches and the skin score at 48 h after TNCB on day 54. The skin symptoms and total IgE levels were also elevated gradually from day 18 to day 54. Chlorpheniramine, cyproheptadine and methysergide caused no effect on the scratching behavior accompanied by skin lesions at 48 h after TNCB challenge, even at a high dose. On the other hand, L-733,060, naloxone, naltrexone, prednisolone and dexamethasone caused a significant inhibition of the scratching behavior induced by TNCB. Therefore, this model may be useful to evaluate the effects of drugs on the itch response accompanied by skin lesions, such as atopic dermatitis.
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PMID:A new chronic itch model accompanied by skin lesions in hairless mice. 1691 33

Itching is the most important symptom in atopic dermatitis because the persistent scratching in response to itching aggravates the disease. However, the etiologic mechanisms of itching in atopic dermatitis remain uncertain. HR-1 hairless mice fed a special diet, HR-AD, develop atopic dermatitis-like symptoms with prolonged scratching episodes. The purpose of this study was to examine whether skin nerve fiber changes were involved in the prolonged scratching seen in this mouse model. On day 56 after the start of feeding, prolonged scratching, as well as atopic dermatitis-like skin changes, were clearly observed in HR-AD-fed mice, while no abnormal changes were observed in mice fed a normal diet. Immunohistochemical analyses of the skin using antibody to protein gene product 9.5 showed the development of numerous immunoreactive nerve fibers in the epidermis of HR-AD-fed mice. Furthermore, after cessation of HR-AD feeding, the reduction in intraepidermal nerve fibers coincided with decreased scratching. Neither the prolongation of scratching nor the increase in intraepidermal nerve fibers was affected by dexamethasone treatment. Thus, the increased number of intraepidermal nerve fibers could be involved in the aggravation of itch-related scratching observed in this model.
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PMID:Development of numerous nerve fibers in the epidermis of hairless mice with atopic dermatitis-like pruritic skin inflammation. 1760 84

Although Hox gene expression has been linked to motoneuron identity, a role of these genes in development of the spinal sensory system remained undocumented. Hoxb genes are expressed at high levels in the dorsal horn of the spinal cord. Hoxb8 null mutants manifest a striking phenotype of excessive grooming and hairless lesions on the lower back. Applying local anesthesia underneath the hairless skin suppressed excessive grooming, indicating that this behavior depends on peripheral nerve activity. Functional ablation of mouse Hoxb8 also leads to attenuated response to nociceptive and thermal stimuli. Although spinal ganglia were normal, a lower postmitotic neural count was found in the dorsalmost laminae at lumbar levels around birth, leading to a smaller dorsal horn and a correspondingly narrowed projection field of nociceptive and thermoceptive afferents. The distribution of the dorsal neuronal cell types that we assayed, including neurons expressing the itch-specific gastrin-releasing peptide receptor, was disorganized in the lumbar region of the mutant. BrdU labeling experiments and gene-expression studies at stages around the birth of these neurons suggest that loss of Hoxb8 starts impairing development of the upper laminae of the lumbar spinal cord at approximately embryonic day (E)15.5. Because none of the neuronal markers used was unexpressed in the adult dorsal horn, absence of Hoxb8 does not impair neuronal differentiation. The data therefore suggest that a lower number of neurons in the upper spinal laminae and neuronal disorganization in the dorsal horn underlie the sensory defects including the excessive grooming of the Hoxb8 mutant.
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PMID:Loss of Hoxb8 alters spinal dorsal laminae and sensory responses in mice. 1843 Jul 98

We reported that the Gly573Ser substitution in transient receptor potential vanilloid 3 (TRPV3) led to increased ion channel activity in keratinocytes and caused spontaneous hairlessness in DS-Nh mice. DS-Nh mice also develop allergic and pruritic dermatitis. As the hairless and dermatitis phenotypes were both inherited in an autosomal dominant fashion and could not be segregated from each other, we speculated that TRPV3(Gly573Ser) might be responsible for the dermatitis. Here, we constructed TRPV3(Gly573Ser) transgenic mice, with a putative promoter sequence in the 5' region of TRPV3, to investigate the involvement of TRPV3 in the development of specific types of dermatitis. These transgenic mice spontaneously developed dermatitis, whereas wild-type mice did not display this phenotype when maintained under the same conditions. Histological and serological analyses were carried out to better understand the clinical features of TRPV3(Gly573Ser) transgenic mice. A physiological study revealed that TRPV3(Gly573Ser) induced a higher nerve growth factor response to heat. Finally, C57BL-Nh mice were used to investigate the penetrance of the TRPV3(Gly573Ser) gene for dermatitis. Interestingly, C57BL-Nh mice developed spontaneous scratching behavior, separately from the development of dermatitis. We propose that TRPV3(Gly573Ser) is a cause of pruritus and/or dermatitis associated with scratching, and suggest that TRPV3 may represent a therapeutic target in pruritic dermatitis.
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PMID:Impact of the Gly573Ser substitution in TRPV3 on the development of allergic and pruritic dermatitis in mice. 1920 53

In patients with atopic dermatitis, alcoholic beverages can sometimes trigger or enhance itching. We have previously reported that HR-1 hairless mice fed a commercial special diet, HR-AD, but not a normal diet, develop atopic dermatitis-like skin inflammation with prolonged spontaneous scratching, and that skin barrier dysfunction is involved in the basal scratching. In the present study, the effects of ethanol on itch-related scratching were examined in this mouse model. When ethanol (30%, 10 ml/kg) was given orally to HR-AD-fed mice, scratching with long duration was further markedly increased, while oral ethanol administration had little effect on the scratching response in normal diet-fed mice. The scratching response after oral ethanol administration in HR-AD-fed mice (ethanol-induced scratching) was attenuated by antagonism of the mu-opioid receptor or local skin anesthesia, as in human itching. Ethanol-induced scratching was also suppressed by improvement of skin barrier function by an application of petrolatum ointment, while ethanol administration itself did not affect the function. This suggests that ethanol indirectly aggravates the basal scratching. Although antagonism of the transient receptor potential vanilloid-1 did not affect ethanol-induced scratching, blockade of ethanol actions in the central nervous system (CNS), including gamma-aminobutyric acid type A receptor antagonism and N-methyl-d-aspartate receptor activation, inhibited it. Taken together, the present study demonstrates that orally administered ethanol markedly aggravates itch-related scratching in HR-AD-fed mice developing atopic dermatitis, and suggests that the CNS depressant actions of ethanol play an important role in the aggravation.
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PMID:Ethanol aggravates itch-related scratching in hairless mice developing atopic dermatitis. 1934 7

The present study was performed to study the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on scratching behavior in hairless mice, which are highly sensitive to pruritogens (mediators causing itching), except for histamine, and are suitable for time-course studies due to their hairless skin. TCDD is a well-known environmental pollutant that causes skin diseases with itching; therefore, we examined whether TCDD induced itching. Oral administration of TCDD caused no increase in scratching behavior when used alone, whereas TCDD in combination with distilled water or acetone/olive oil application caused a significant increase in scratching behavior. Furthermore, nerve growth factor (NGF) content in the skin increased significantly. A single administration of chlorpheniramine (histamine H1 receptor antagonist), tranilast (chemical mediator release inhibitor) and olopatadine (histamine H1 receptor antagonist) had no effect on scratching behavior induced by TCDD in combination with acetone/olive oil application. With repeated administration for 7 days, chlorpheniramine and tranilast had no effect on scratching behavior, whereas olopatadine significantly inhibited scratching behavior. In addition, only olopatadine significantly inhibited NGF content in the skin. From these findings, it can be concluded that TCDD is not a pruritogen but causes alloknesis (itchy skin) with the simultaneous use of trivial external stimulation. In addition, it was found that drugs which decreased skin NGF contents may inhibit this scratching behavior.
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PMID:Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on scratching behavior in mice. 1996 4


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