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)

Since the majority of itching skin diseases are inflammatory or allergic, it has been assumed that release or activation of inflammatory mediators, stimulating the itch receptors, play an essential role in the pathophysiology of itch. In this review some of the possible mediators are discussed. Histamine induces itch upon intradermal injection, but urticaria is the only itching dermatosis which is significantly relieved by antihistamines. Serotonin is much weaker than histamine in provoking itch upon intradermal injection. Serotonin acting in synergism with prostaglandins may cause itch in polycythaemia vera. Neuropeptides release histamine from skin mast cells, but it remains to be determined whether neurogenic peptides are responsible for clinical pruritus. Prostaglandins enhance pruritus induced by intradermal histamine (and serotonin) but are weak pruritogens per se. Lymphocytes are present in many itching skin diseases and it could be assumed that lymphokines are involved in the pathogenesis of itch. Supporting this theory is the finding that ciclosporin A, an inhibitor of lymphokine production, reduces itch in atopic dermatitis. Central mechanisms are essentially unknown, but there are indications that opioid peptides might be involved in the central transmission of itch.
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PMID:Peripheral and central mediators of itch. 157 79

To study the nasal response to serotonin, 14 asymptomatic hay fever patients received intranasal serotonin in increasing doses. Itching and the number of sneezes were noted, and the amount of secretion was measured and assayed for substance P. Nasal airway resistance was recorded by active posterior rhinomanometry. Serotonin induced a dose-dependent increase in nasal itching, number of sneezes and secretion. Substance P was found in 41 of 42 secretions. The median concentration was 10.3 pmol/l (range 0-28.9), and increased parallel to increasing doses of serotonin (P less than 0.001).
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PMID:Nasal challenge with serotonin in asymptomatic hay fever patients. 244 28

In order to study the nasal response to serotonin, 14 normal persons, in a double-blind study, were provoked in the nose with serotonin and histamine. Itching and the number of sneezes were noted, the amount of secretion measured, and nasal airway resistance recorded by active posterior rhinomanometry. Serotonin induced significant nasal itching, sneezing and hypersecretion, similar to the effects of histamine. The effect of serotonin on nasal airway resistance, on the other hand, was slight (+ 10%) and insignificant in contrast to that of histamine in equipotent doses (+ 48%) (P less than 0.001). In conclusion, we have shown that serotonin provocation can induce a rhinitis response in the human nose. The nasal symptoms suggest an effect on sensory nerves with reflex-induced sneezing and hypersecretion, while there appears to be little direct effect on capacitance vessels. The possible role of serotonin as a mediator of rhinitis remains speculative.
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PMID:Nasal challenge with serotonin and histamine in normal persons. 403 56

Ten women with recurrent migraine-like headache, flush, urticaria and itching excoriations were put on a protein/tryptophan reduced diet. The 5-HT uptake kinetics in platelets, the frequency of headache attacks and skin symptoms were recorded. On customary food the 5-HT uptake kinetics were severely disturbed. On diet, the platelet 5-HT uptake was normalized and, in parallel, the migraine-like symptoms and skin manifestations were reduced. The parallel between the improvement in active 5-HT uptake by platelets and clinical symptoms during dietary protein/tryptophan restriction supports the idea that impairment of the 5-HT uptake in platelets is a contributory factor in the pathogenesis of migraine-like headache and other 5-HT related symptoms.
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PMID:Effects of dietary protein-tryptophan restriction upon 5-HT uptake by platelets and clinical symptoms in migraine-like headache. 664 Jun 53

The objective of the present study was to determine whether ondansetron, a specific serotonin type 3 receptor antagonist (5-HT3), relieves cholestatic pruritus in patients resistant to conventional antipruritic therapy (antihistamines and cholestyramine). In a placebo-controlled study the acute effect of an intravenous injection of ondansetron (4 mg, 8 mg) or placebo (NaCl solution) was tested in 10 patients (41-66 years of age; 4 men, 6 women) with cholestatic itch. A successful treatment was assessed when the intensity of itch was reduced by 50% or more within 2 h after injection of ondansetron. Intensity of itch was determined by the patients on a visual rating scale from 0 to 10. Ondansetron reduced or abolished pruritus within 30-60 min after injection. A 50% reduction of the intensity of itch was observed up to 6 h after injection of 8 mg. The effect was reproducible in the same patient. In conclusion ondansetron is effective in the treatment of cholestatic itch. Serotonin may participate in the generation and/or sensation of cholestatic pruritus.
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PMID:Relief of cholestatic pruritus by a novel class of drugs: 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists: effectiveness of ondansetron. 764 46

Pruritus is a common, unpleasant symptom of uremic patients. Serotonin and histamine have been reported as possible mediators ofuremic pruritus, and ondansetron is a potent and selective inhibitor of 5-HT3 receptors. The aims of our study were (1) to evaluate the effect of ondansetron on uremic pruritus in continuous ambulatory peritoneal dialysis (CAPD) patients and its safety and (2) to investigate the role of histamine and serotonin in uremic pruritus. To study the prevalence and pathogenesis of uremic pruritus, CAPD and hemodialysis (HD) patients were asked to complete a pruritus questionnaire. The replies were scored based on numerical scales, and the results were evaluated by the same investigator who did not know the patients. Pruritus was graded, according to the total points for each patient, as mild, moderate, or severe. Of 54 patients on HD, 29 (53.7%) had pruritus, and of 43 patients on CAPD, pruritus was present in 21 (48.8%). In HD patients, pruritus was mild in 14 (48.3%), moderate in 12 (41.4%), and severe in 3 (10.3%) patients; the distribution in CAPD patients was 9 (42.9%), 10 (47.6%), and 2 (9.5%), respectively. There was no correlation between the presence and severity of pruritus and age, sex, primary renal disease, duration of dialysis, dialysis solutions used, and hematological and biochemical parameters except for serum histamine and serotonin levels and their product. Plasma histamine levels in CAPD patients were 13.1 +/- 1.1 ng/ml in pruritic and 11.0 +/- 3.9 ng/ml in nonpruritic patients (p = 0.06), serum serotonin levels were 115.6 +/- 43.3 ng/ml and 64 +/- 42.3 ng/ml (p < 0.05), respectively, and the histamine x serotonin product was 1,461 +/- 576 and 646 +/- 545 (p < 0.01), respectively. Eleven CAPD patients (6 males, 5 females) with a mean age of 66 (range 33-83) years and an average time on CAPD of 18 (range 3-31) months with moderate to severe pruritus were treated with ondansetron (4 mg twice daily p.o.) for a mean period of 3 (range 1-5) months. All patients responded to the treatment. There was a significant reduction of the severity of pruritus from the start of treatment, and on the 3rd day the pruritic score (mean value) was 10 (range 5-19) points, while at time 0 (before treatment) it was 26 (range 19-37) points (p < 0.0001). Pruritus disappeared in 7 patients at the end of the 1st week and in all patients at the end of the 2nd week of treatment. This effect was maintained during the study. Plasma histamine levels decreased significantly during the treatment from 12.9 +/- 1.2 to 6.7 +/- 5.9 ng/ml (p < 0.05). Also, serum serotonin levels were reduced from 125.1 +/- 47.8 to 59.3 +/- 27.5 ng/ml (p < 0.05) at the end of the 1st month of treatment, and the histamine x serotonin product showed a more significant reduction: from 1,544 +/- 656 to 454 +/- 436 (p < 0.01). Three patients reported an improvement in their nausea and vomiting during the treatment. Weekly clinical and laboratory examinations showed no side effects, adverse reactions, or other complications. Our data indicate that ondansetron is an effective, safe, and well-tolerated drug for the treatment of uremic pruritus in CAPD patients and that histamine and serotonin may have a crucial role in the appearance or perception of the uremic pruritus.
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PMID:Histamine and serotonin in uremic pruritus: effect of ondansetron in CAPD-pruritic patients. 957 65

Serotonin (5-HT) is pruritogenic in humans and suggested to be involved in some pruritic diseases. Our experiments were carried out to determine whether an intradermal injection of 5-HT would elicit itch-associated response in mice and to elucidate the 5-HT receptor subtypes involved in this 5-HT action. 5-HT (14.1-235 nmol site(-1)) injected intradermally into the rostral back elicited scratching of the injected site, with bell-shaped dose-response relationship. The scratching induced by 5-HT (100 nmol site(-1), peak effective dose) was suppressed by capsaicin (repeated administration) and the opioid antagonist naloxone, features being similar to human itching. Scratching was also elicited by the 5-HT2 receptor agonist alpha-methylserotonin, but not by the 5-HT1A receptor agonist R(+)-8-hydroxy-N,N-dipropyl-2-aminotetralin nor the 5-HT3 receptor agonists 2-methylserotonin and 1-phenylbiganide. Scratching induced by 5-HT and alpha-methylserotonin was inhibited by peroral pretreatment with 5-HT1/2 receptor antagonists methysergide and cyproheptadine. 5-HT-induced scratching was also inhibited by intradermal injection of methysergide. Peroral pretreatment with 5-HT3 receptor antagonists ondansetron and 3-tropanyl-3, 5-dichrobenzoate did not significantly suppress 5-HT-induced scratching. The results suggest that scratching induced by intradermal injection of 5-HT is itch-associated response. The 5-HT action may be mediated at least partly by cutaneous 5-HT2 receptors.
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PMID:Itch-associated response induced by intradermal serotonin through 5-HT2 receptors in mice. 1061 11

Capsaicin (CAP) has been demonstrated to be an effective topical inhibitor of cutaneous vasodilatation, pain and pruritus induced by a variety of chemical and physical stimuli. In a previous study, we showed a significantly inhibitory effect of topical CAP treatment on histamine-induced itch and cutaneous vascular reactions in healthy subjects compared to atopic eczema patients. As serotonin is proposed to play a pathophysiological role in some types of pruritus (e.g. uremic and hepatic pruritus) and CAP has been described to be successful in hemodialysis-related pruritus, we investigated the antipruritic effect of topical CAP on serotonin-induced reactions in 10 healthy volunteers in comparison to untreated skin (UPS) and placebo substance (vehicle)-treated skin (VS). On the first day, serotonin iontophoresis was performed in untreated skin. One week later, the treatments started, using either CAP 0.05% liniment or a placebo liniment (vehicle) 3 times daily over a 5-day period. On day 6, serotonin was applied by iontophoresis within the pretreated skin. After another 1-week break, the treatments were performed vice versa on the corresponding infrascapular region. Weal and flare areas were planimetrically evaluated. Itch sensations were documentated by the volunteer on a scale over a 24-min follow-up period. The examination also comprised alloknesis, which stands for induction of perifocal sensations by usually non-itching stimuli. In CAP-treated skin, serotonin-induced wheals were significantly larger post-application compared to non-pretreated skin. Wheals were significantly larger in VS than in UPS. Comparison of serotonin-induced flares in the different study arms did not reveal any significant differences. Itch sensations were not significantly reduced by topical CAP application. The areas of alloknesis were smaller in capsaicin-treated skin compared to VS and UPS, but did not reach significant value. In conclusion, topical CAP application is not effective in serotonin-induced itching in healthy volunteers. Serotonin is most unlikely to play a role in the mechanism of action of CAP.
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PMID:Lack of efficacy of topical capsaicin in serotonin-induced itch. 1065 61

Pruritus is a distressing symptom affecting up to 90% of dialysis patients. Conventional treatment with antihistamines is often ineffective and may have unacceptable side effects. Serotonin (5-hydroxytryptamine type 3 [5-HT(3)]) is known to enhance pain perception and pruritic symptoms through receptors on sensory nerve endings. Antagonism of 5-HT(3) receptors may be of use in treating uremic pruritus. We randomly assigned 16 hemodialysis patients with persistent pruritus to treatment with the 5-HT(3)-receptor antagonist, ondansetron (8 mg), or placebo three times daily for 2 weeks each in a prospective, placebo-controlled, double-blind crossover study. Patients scored their intensity of pruritus daily on a 0-to-10 visual analogue scale (0 = no pruritus, 10 = maximal pruritus), and daily use of antihistamines as escape medication was recorded. The median daily pruritus score did not change significantly during active or placebo treatment (preondansetron, 5. 3; interquartile range [IQR], 3.4 to 6.3; during ondansetron, 3.9; IQR, 2.7 to 5.0; P = not significant; preplacebo, 3.7; IQR, 3.0 to 4. 6; during placebo, 3.6; IQR, 2.4 to 4.8; P = not significant). The median daily percentage of escape medication use decreased from 21% (IQR, 9 to 61) to 9% (IQR, 0 to 33) with ondansetron (P = not significant) and from 53% (IQR, 0 to 88) to 5% (IQR, 0 to 31) with placebo (P = not significant). There was no difference in predialysis biochemistry test results or dialysis efficacy during treatment phases. Ondansetron does not improve pruritus in hemodialysis patients. Use of antihistamines decreased with both ondansetron and placebo.
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PMID:Ondansetron therapy for uremic pruritus in hemodialysis patients. 1079 15

To clarify the behavioral and pathological features of spontaneous scratching of NC mice with mite-induced chronic dermatitis, we investigated the spontaneous and pruritogen-evoked scratching of NC mice. Although the frequency of scratching of NC mouse did not increase under specific pathogen-free environment, it gradually and markedly increased from 3 to 6 weeks after transfer to conventional environment. The onset of increase in spontaneous scratching was similar to that of dermatitis development and the elevation of plasma concentration of immunoglobulin E. At chronic stage (16 weeks after environment change), the frequency of spontaneous scratching was roughly parallel to the degree of dermatitis, but not to the plasma concentration of immunoglobulin E. The spontaneous scratching of NC mice with dermatitis was inhibited by distraction and the opioid antagonist naltrexone, suggesting that the scratching is itch-associated response. An intradermal injection of serotonin, but not histamine and substance P, elicited scratching of the injected site. Methysergide and cyproheptadine inhibited the serotonin-induced scratching but not spontaneous scratching. The results suggest that marked elevation of plasma immunoglobulin E is not always the cause of spontaneous itch-associated response of NC mice with dermatitis. Serotonin, histamine and substance P may not play an important role in spontaneous itch-scratch response at a chronic stage.
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PMID:Characterization of itch-associated responses of NC mice with mite-induced chronic dermatitis. 1115 60


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