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

We investigated a spinal site for opioid modulation of itch-related scratching behavior in rats. Intradermal 5-HT (2%, 10 microl) elicited intermittent bouts of hindlimb scratching directed toward the injection site (nape of neck) beginning within minutes and lasting >1 hr. 5-HT-evoked scratching was significantly reduced by systemic administration of the opiate antagonist naltrexone but was not affected by systemic morphine at a dosage (3 mg/kg) that induces analgesia. Intradermal 5-HT elicited a significant increase in c-fos-like immunoreactivity (FLI) in superficial laminas I-III at the lateral aspect of the cervical C3-C6 dorsal horn compared with controls receiving intradermal saline. Neither systemic morphine nor naltrexone significantly affected counts of 5-HT-evoked FLI. The lack of effect of morphine suggests that intradermal 5-HT activates dorsal horn neurons, signaling itch but not pain. Attenuation of 5-HT-evoked scratching but not spinal FLI by naltrexone suggests a supraspinal site for its antipruritic action. In contrast, morphine significantly attenuated FLI elicited by intradermal capsaicin, a chemical that induces pain but not scratching.
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PMID:Opioid modulation of scratching and spinal c-fos expression evoked by intradermal serotonin. 1464 70

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

We performed a retrospective study that compared the efficacy and safety of dexamethasone (DEX) 8 mg with DEX 16 mg in cases of acute and delayed emesis induced by cisplatin (CDDP) chemotherapy in patients with lung cancer. Sixty-eight lung cancer patients treated with combination cisplatin, ifosfamide, and irinotecan therapy were studied. The DEX 8 mg group and the DEX 16 mg group received DEX intravenous injection 30 min prior to CDDP. All patients then received a 5-HT(3) antagonist intravenous injection 30 min before CDDP. Protection from acute nausea (day 1) was significantly superior in the DEX 16 mg group compared with the DEX 8 mg group (DEX 8 mg, 76.5%; DEX 16 mg, 100%). Protection from delayed emesis (day 1) was significantly superior in the DEX 16 mg group compared with the DEX 8 mg group. There was no reported severe nausea (grade 3) and vomiting (grade 2) in the DEX 16 mg group. Furthermore, perphenazine hydrochloride for use as rescue medication was required by significantly fewer patients in the DEX 16 mg group than in the DEX 8 mg group (DEX 8 mg, 41.2%; DEX 16 mg, 0%). Adverse effects were observed in 10 cases (nine reports of generalized fatigability, two of headache) in the DEX 8 mg group and in 16 cases (11 reports of generalized fatigability, one of pruritus) in the DEX 16 mg group. However, because the symptoms were all mild, we did not consider that there was any safety problem. In conclusion, DEX 16 mg is a clinically useful treatment for acute and delayed emesis induced by cisplatin-induced chemotherapy in patients with lung cancer.
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PMID:[Comparison of dexamethasone 8 mg and 16 mg for the prevention of acute and delayed cisplatin-induced emesis in patients with lung cancer]. 1639 51

This study investigated endogenous mediators involved in mosquito allergy-associated itching in mice. An intradermal injection of an extract of mosquito salivary gland elicited marked scratching in sensitized mice. The 5-lipoxygenase inhibitor zileuton (100 mg/kg), the 5-lipoxygenase activating peptide inhibitor MK-886 (10 mg/kg), and the glucocorticoid betamethasone 17-valerate (3 mg/kg) inhibited the scratching. The scratching was not affected by the cyclooxygenase inhibitors indomethacin and ketoprofen, the TP prostanoid receptor antagonist SQ-29548, the leukotriene B(4) antagonist ONO-4057, the cysteinyl leukotriene antagonist pranlucast, the leukotriene D(4) antagonist MK-571, the platelet-activating factor antagonist CV-3988, the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester, the H(2) histamine-receptor antagonist cimetidine, the H(1) histamine-receptor antagonist terfenadine plus cimetidine, and cypoheptadine that blocks the 5-HT(1/2) serotonin receptors. Zileuton (100 mg/kg) inhibited the increased activity of the cutaneous nerve branch induced by an intradermal injection of the extract, suggesting the peripheral action. Zileuton and MK-886 (10 and 100 microM) did not affect high K(+)-induced increase in intracellular Ca(2+) concentration in cultured dorsal root ganglion neurons. The results suggest that 5-lipoxygenase metabolite(s) other than leukotriene B(4) and cysteinyl leukotrienes are involved in mosquito allergy-associated itching.
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PMID:Possible involvement of 5-lipoxygenase metabolite in itch-associated response of mosquito allergy in mice. 1782 70

Pruritus occurs frequently following opioid use, particularly after neuraxial administration. Although not life threatening, pruritus is discomforting and may decrease patient satisfaction. Even though the mechanism of opioid-induced pruritus is not yet fully understood, there is increasing evidence of the important role played by micro opioid receptors. Animal experiments pointing to the role of the micro opioid receptor and the efficacy of micro opioid receptor antagonists for opioid adverse effect prophylaxis and treatment have been replicated in several studies. Serotonin and dopamine D(2) receptors, prostaglandins and spinal inhibitory pathways may also be involved in the genesis of pruritus. Several pharmacological agents have been used both for the treatment of established pruritus and in its prevention. Of these, micro opioid receptor antagonists have been most consistent in terms of attenuating opioid-induced pruritus but present problems in dose and administration. Other drugs, including mixed opioid receptor agonist-antagonists, serotonin 5-HT(3) receptor antagonists, propofol, NSAIDs and D(2) receptor antagonists, have also been demonstrated to be useful. This review summarises the current understanding of the mechanisms causing opioid-induced pruritus and the pharmacological therapies available to prevent and/or manage this disorder.
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PMID:Pathophysiology and management of opioid-induced pruritus. 1798 54

Herbex-kid (HK), a polyherbal formulation was evaluated in various experimental allergic models of Type I hypersensitivity reactions. Compound 48/80 (C 48/80) has been shown to induce rat mesentery mast cell degranulation and HK (1.07, 10.75 and 107.5 mg ml(-1)) inhibited the mast cell degranulation in a dose dependent manner. HK (1.07, 10.75 and 107.5 mg kg(-1); p.o.) showed dose-dependent protection against C 48/80 induced systemic anaphylaxis in male Balb/C mice. In active anaphylaxis model, male Wistar rats orally administered with 10.75 and 107.5 mg kg(-1) of HK showed significant (P < 0.01) protection against mast cell degranulation, while in passive anaphylaxis model, only at 107.5 mg kg(-1) showed significant (P < 0.01) reduction in mast cell degranulation. HK at all dose levels was able to significantly decrease the time spent in nasal rubbing in Wistar rats sensitized to ovalbumin, while only at 107.5 mg kg(-1) it showed significant (P < 0.01) reduction in number of sneezes. In C 48/80-induced skin itch model, all dose levels of HK significantly (P < 0.001) decreased the time spent in itching and the number of itches. HK did not produce any significant inhibition in histamine induced contraction in guinea pig ileum. From the above findings we conclude that the HK possesses antiallergic activity mediated by reducing of the release mediators from mast cells and also by 5-HT antagonism without the involvement of histamine (H1) receptors.
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PMID:Herbex-kid Inhibits Immediate Hypersensitivity Reactions in Mice and Rats. 1883 Apr 58

Protease-activated receptor (PAR)-2 and PAR-4 are implicated in nonhistaminergic itch. We investigated dose dependence, tachyphylaxis, and cross-tachyphylaxis of itch-associated scratching elicited by intradermal injections of PAR-2 and PAR-4 agonists, serotonin (5-hydroxytryptamine, 5-HT), and histamine in ICR mice, as well as mu-opioid modulation of PAR-2 agonist-evoked scratching. Each agent elicited dose-related increases in scratch bouts. Scratching elicited by the PAR-4 agonist and histamine both exhibited significant tachyphylaxis but no cross-tachyphylaxis with each other. Scratching evoked by 5-HT did not exhibit significant tachyphylaxis but did exhibit significant cross-tachyphylaxis to scratching evoked by the PAR-2 and PAR-4 agonists and histamine. Naltrexone and high-dose morphine (10 mg/kg) attenuated PAR-2 agonist-evoked scratching, whereas lower dose morphine (1 mg/kg) had no effect. High-dose morphine also significantly increased circling behavior, which may have interfered with scratching. The PAR-2 agonist and 5-HT produced overlapping distributions of Fos-like immunoreactivity in the superficial dorsal horn. These results indicate that PAR-2 and PAR-4 agonists, histamine, and 5-HT elicit itch-related scratching and activate superficial dorsal horn neurons that may participate in scratch reflex and ascending itch signaling pathways.
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PMID:Scratching behavior and Fos expression in superficial dorsal horn elicited by protease-activated receptor agonists and other itch mediators in mice. 1929 90

Itch, an unpleasant sensation associated with the desire to scratch, is symptomatic of dermatologic and systemic disorders that often resist antihistamine treatment. Histamine-independent itch mediators include serotonin (5-HT) and agonists of the protease-activated receptor-2 (PAR-2). We used behavior, Fos immunohistochemistry, and electrophysiology to investigate if these mediators activate spinal dorsal horn neurons in a manner consistent with itch. Intradermal (i.d.) injection of the PAR-2 agonist SLIGRL-NH(2) in the rostral back evoked bouts of directed hindlimb scratches over 20-30 min. Hindpaw injection of SLIGRL-NH(2) produced Fos staining in superficial dorsal horn which was then targeted for single-unit recording. Small id microinjections of SLIGRL-NH(2) or 5-HT identified responsive single units in the superficial dorsal horn of mice anesthetized with pentobarbital. Thirty-eight units characterized as wide dynamic range, nociceptive specific, or mechanically insensitive exhibited significantly increased firing after i.d. SLIGRL-NH(2) for 9 min, to partial (25%) tachyphylaxis with repeated injection. A majority additionally responded to 5-HT (70%), mustard oil (79%), and capsaicin (71%). Seven units isolated with the 5-HT search stimulus exhibited significant and prolonged responses to 5-HT with tachyphylaxis to repeated injections. The majority also responded to SLIGRL-NH(2), mustard oil, and capsaicin. The prolonged responses of superficial dorsal horn neurons to SLIGRL-NH(2) and 5-HT suggest a role in signaling itch. However, their responsiveness to algogens is inconsistent with itch specificity. Alternatively, such neurons may signal itch, whereas noxious stimulus levels recruit these and a larger population of pruritogen-insensitive cells to signal pain which masks or occludes the itch signal.
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PMID:Activation of superficial dorsal horn neurons in the mouse by a PAR-2 agonist and 5-HT: potential role in itch. 1945 38

The mechanisms that generate itch are poorly understood at both the molecular and cellular levels despite its clinical importance. To explore the peripheral neuronal mechanisms underlying itch, we assessed the behavioral responses (scratching) produced by s.c. injection of various pruritogens in PLCbeta3- or TRPV1-deficient mice. We provide evidence that at least 3 different molecular pathways contribute to the transduction of itch responses to different pruritogens: 1) histamine requires the function of both PLCbeta3 and the TRPV1 channel; 2) serotonin, or a selective agonist, alpha-methyl-serotonin (alpha-Me-5-HT), requires the presence of PLCbeta3 but not TRPV1, and 3) endothelin-1 (ET-1) does not require either PLCbeta3 or TRPV1. To determine whether the activity of these molecules is represented in a particular subpopulation of sensory neurons, we examined the behavioral consequences of selectively eliminating 2 nonoverlapping subsets of nociceptors. The genetic ablation of MrgprD(+) neurons that represent approximately 90% of cutaneous nonpeptidergic neurons did not affect the scratching responses to a number of pruritogens. In contrast, chemical ablation of the central branch of TRPV1(+) nociceptors led to a significant behavioral deficit for pruritogens, including alpha-Me-5-HT and ET-1, that is, the TRPV1-expressing nociceptor was required, whether or not TRPV1 itself was essential. Thus, TRPV1 neurons are equipped with multiple signaling mechanisms that respond to different pruritogens. Some of these require TRPV1 function; others use alternate signal transduction pathways.
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PMID:TRPV1-expressing primary afferents generate behavioral responses to pruritogens via multiple mechanisms. 1956 17


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