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PubMed2006

Nalfurafine, a kappa opioid receptor agonist, inhibits scratching behavior secondary to cholestasis induced by chronic ethynylestradiol injections in rats.

Scratching is the behavioral manifestation of pruritus. The pruritus of cholestasis can be severe, intractable and affect the quality of life. We investigated if ethynylestradiol (EE)-induced cholestasis is associated with scratching in rats and if nalfurafine, a kappa opioid receptor agonist with antipruritic effects in human uremic pruritus, would antagonize such scratching. Chronic injection of EE (2 mg/kg, s.c., for 14 days) induced cholestasis as documented by increased serum concentrations of bile acids and caused a higher incidence of body scratching compared to vehicle, thus providing an animal model to study scratching behavior secondary to cholestasis. Pretreating the rats with nalfurafine (0.005-0.04 mg/kg, s.c.) inhibited EE-induced scratching dose-dependently with an A(50) value of 0.013 (0.009-0.021) mg/kg. Serum levels of dynorphin A and nitric oxide were decreased in rats with cholestasis compared to control animals. Our data suggest that (a) nalfurafine has the potential to relieve cholestatic pruritus and (b) both kappa opioid and nitric oxide systems are involved, at least in part, in mediating the pruritus of cholestasis.

Animals↗

PubMed2006

Role of COX-1 and COX-2 on skin PGs biosynthesis by mechanical scratching in mice.

We examined the involvement of cyclooxygenase (COX)-1 and COX-2 on mechanical scratching-induced prostaglandins (PGs) production in the skin of mice. The dorsal regions of mice were scratched using a stainless brush. COXs expressions in the skin were analyzed using real-time PCR and Western blotting. The effect of acetylsalicylic acid (ASA) on the ability of PGs production were determined based on skin PGs level induced by arachidonic acid (AA) application. Mechanical scratching increased PGD2, PGE2, PGI2 and PGF(2 alpha). COX-1 was constitutively expressed and COX-2 expression was enhanced by scratching. Intravenous administration of ASA inhibited PGs biosynthesis in the normal skin. PGs levels of the skin 6h after ASA administration (ASA 6 h) were almost equal to those of the skin 10 min after ASA administration (ASA 10 min). In the scratched skin, AA-induced PGE2 and PGI2 of ASA 6 h were significantly higher than those of ASA 10 min. The skin PGD2 and PGF(2 alpha) of ASA 10 min were almost same to those of ASA 6 h. In the normal skin of COX-1-deficient mice, skin PGD2 level was lower than that of wild-type mice, although PGE2, PGI2 and PGF(2 alpha) levels were almost equal to those of wild type. In the scratched skin of COX-1-deficient mice, PGD2, PGE2, PGI2 and PGF(2 alpha) levels were lower than those of wild-type mice. These results suggested that cutaneous PGD2 could be mainly produced by COX-1, and PGE2 and PGI2 could be produced by COX-1 and COX-2, respectively, in mice.

Animals↗

PubMed2001

Roles of mast cells and sensory nerves in cutaneous vascular hyperpermeability and scratching behavior induced by poly-L-arginine in rats.

We investigated whether the polycation poly-L-arginine elicited cutaneous vascular hyperpermeability and scratching behavior and, if so, whether these responses involved mast cells and sensory nerves in rats. Intradermal injections of poly-L-arginine induced vascular hyperpermeability and scratching behavior. Combined treatment with chlorpheniramine and methysergide almost completely suppressed the poly-L-arginine (50 microg/site)-induced plasma leakage. Capsaicin desensitization and the tachykinin NK(1) receptor antagonist LY303870, (R)-1-[N-(2-methoxybenzyl)acetylamino]-3-(1H-indol-3-yl)-2-[N-(2-(4-(piperidin-1-yl)piperidin-1-yl)acetyl)amino]propane, partially inhibited the leakage. In mast cell-deficient rats, poly-L-arginine only minimally induced plasma leakage. On the other hand, capsaicin desensitization and LY303870, but not chlorpheniramine or methysergide, suppressed the poly-L-arginine (200 microg/site)-induced scratching. Moreover, poly-L-arginine elicited the scratching even in mast cell-deficient rats. These results suggest that substance P is at least partly involved in both the cutaneous plasma leakage and the scratching behavior induced by poly-L-arginine. Moreover, mast cell-derived amines are suggested to be involved in the plasma extravasation but scarcely, if any, in the scratching behavior.

Animals↗

PubMed2003

Evaluation of the effects of anti-pruritic drugs on scratch responses using histamine H1 receptor-deficient mice.

The effects of anti-pruritic drugs on scratching behavior associated with passive cutaneous anaphylaxis in histamine H(1) receptor-deficient and wild-type mice were studied. Passive sensitization with mouse monoclonal anti-dinitrophenyl-immunoglobulin E (IgE) resulted in an increase in the incidence of scratching behavior induced by intravenous injection of dinitrophenyl-ovalbumin in both wild-type and histamine H(1) receptor-deficient mice. The histamine H(1) receptor antagonist diphenhydramine inhibited scratching behavior induced by antigen in passively sensitized wild-type mice, whereas no effect was observed in histamine H(1) receptor-deficient mice. On the other hand, oxatomide inhibited scratching behavior in both mice, although the effect in wild-type mice was more potent than that in histamine H(1) receptor-deficient mice. Tranilast inhibited scratching behavior with the same potency in both mice. We concluded that the scratching behavior associated with passive cutaneous anaphylaxis involves not only histamine H(1) receptors but also other chemical mediators. Furthermore, the results of the present study indicated that oxatomide has an antagonistic effect on histamine H(1) receptors as well as anti-pruritic effect in vivo.

Animals↗

PubMed2003

Scratch hardness and chipping of dental ceramics under different environments.

OBJECTIVE: The goal of this program was to identify promising environments that could efficiently minimize machining-induced damage of dental materials. METHODS: Single point abrasion (SPA) scratch testing was used on five materials to determine the scratch hardness and amount of edge chipping as functions of chemical environment, including air, water, saline and glycerol solutions. Limited testing was also done under additional environments expected to promote chemomachining effects via crack growth promotion or debris removal. A conical diamond indenter and a conventional tungsten carbide machining tool were used in the scratch tests. One-way ANOVA analysis was used to determine statistical differences among the variables. RESULTS: There was a consistent trend across materials that the water and saline yielded the lowest values of scratch hardness, air the next lowest, and the tests performed in glycerol yielded the highest hardness values. The measured hardness values using the conical diamond tool in the glycerol environments were about twice the hardness values measured under water and saline solutions. Environmental effects on chipping were minimal, but a linear relationship between load and per cent chipping was determined for the WC tool within the 10-50 N test range. The choice of scratch tool strongly affected scratch hardness and chipping tendency. SIGNIFICANCE: The chemical environment had an effect on machining characteristics, but the effects were more dependent on tool interactions rather than material specific properties. As a result, it may not be possible to utilize a particular single environment to substantially improve the damage response of dental materials to machining operations. Improvements in damage resistance can be environmentally obtained, but only for shallow cuts (finishing operations).

Air↗

PubMed1998

The epidemiology of bite and scratch injuries by vertebrate animals in Switzerland.

Pet and wildlife populations are a potential source of various public health problems, and injuries and complications due to animal bites and scratches are the most obvious. As no population based data on the frequency of animal bites were available at a national level in Switzerland, a study was conducted by the Swiss Sentinel Surveillance Network. The objectives of this study were to estimate the incidence of medical consultations due to bite and scratch injuries in humans caused by vertebrate animals, to identify possible risk factors, and to assess bite management habits in primary health care. An annual bite and scratch incidence rate of 325 per 100,000 population was estimated. Consultations peaked during the summer months and geographical differences in the reported incidence were observed. Dogs accounted for more than 60% and cats for about 25% of all cases reported. Animal bites and scratches were frequent in persons under 20 years of age. In most ages, the incidence was higher among women than among men, but not in children under the age of ten years. The incidence of cat bites was especially high in adult women. Bites to the head and neck were most frequent in infants and young children and accounted for approximately one third of the reported cases in this age group. Patients sought medical care principally for primary wound care (52.0%) and for vaccination advice (29.6%). Rabies postexposure prophylaxis was initiated in 1.1% of patients. Wound infection was reported in 10.9% of cases, with cat bites/scratches being more often infected than injuries due to dogs. Hospitalization was reported in 0.3 % of patients. Data from the emergency department of two district hospitals showed that head and neck injuries were more frequent in out-patients and a higher proportion of persons presented with wound infections (14.1%). The hospitalization rate for emergency department visits was 4.7%. Animal bites and scratches are common events in Switzerland. They represent a public health issue of growing importance due to the steadily increasing pet population. A practice based sentinel surveillance system may be an appropriate tool to monitor national trends in animal bites and scratches.

Adolescent↗

PubMed2000

An experimental itch model in monkeys: characterization of intrathecal morphine-induced scratching and antinociception.

BACKGROUND: The most common side effect of spinal opioid administration is pruritus, which has been treated with a variety of agents with variable success. Currently, there are few animal models developed to study this side effect. The aim of this study was to establish a nonhuman primate model to pharmacologically characterize the effects of intrathecal administration of morphine. METHODS: Eight adult rhesus monkeys were used. Scratching responses were videotaped and counted by observers who were blinded to experimental conditions. Antinociception was measured by a warm-water (50 degrees C) tail-withdrawal assay. The dose-response of intrathecal morphine (1-320 microg) for both scratching and antinociception in all subjects was established. An opioid antagonist, nalmefene, was administered either intravenously or subcutaneously to assess its efficacy against intrathecal morphine. RESULTS: Intrathecal morphine (1-32 microg) increased scratching in a dose-dependent manner. Higher doses of intrathecal morphine (10-100 microg) produced thermal antinociception in a dose-dependent manner. On the other hand, nalmefene (10-32 microg/kg intravenously) attenuated maximum scratching responses among subjects. Pretreatment with nalmefene (32 microg/kg subcutaneously) produced approximately 10-fold rightward shifts of intrathecal morphine dose-response curves for both behavioral effects. CONCLUSIONS: These data indicate that intrathecal morphine-induced scratching and antinociception are mediated by opioid receptors. The magnitude of nalmefene antagonism of intrathecal morphine is consistent with microL opioid receptor mediation. This experimental itch model is useful for evaluating different agents that may suppress scratching without interfering with antinociception. It may also facilitate the clarification of mechanisms underlying these phenomena.

Analgesics, Opioid↗

PubMed1997

The scratch test is unreliable for detecting the liver edge.

To determine the validity and reliability of the scratch test method for estimating the liver span below the right costal margin, we performed a prospective double-blind study using multiple examiners at different levels of training. Twenty-two patients were examined by 11 observers using only the scratch test. Measures of liver edge length below the right costal margin using the scratch test were compared with those by ultrasound. The validity of the scratch test was determined by simple linear regression and the concordance correlation coefficient. There was very poor correlation between the scratch test estimates and ultrasound measurements for all examiners. Measurement reliability, estimated using generalizability theory, for seven observers who examined the same nine patients was 0.68. The reliability of a single examiner was 0.24. The scratch test method for measuring the liver edge span below the right costal margin was neither a valid nor reliable method of physical examination.

Adult↗

PubMed2004

Vital role of the itch-scratch response in development of spontaneous dermatitis in NC/Nga mice.

BACKGROUND: The itch sensation and the resultant response, scratching, are important symptoms of atopic dermatitis (AD) and have a significant impact on the quality of life of affected patients. However, the influence of the itch-scratch response on the pathology of AD has not been precisely elucidated. OBJECTIVES: To investigate the role of scratching behaviour in the development of spontaneous dermatitis using conventionally raised NC/Nga mice (Conv-NC mice), which are known to be an animal model for human AD. METHODS: Capsaicin-sensitive sensory nerves of the mice were ablated by neonatal capsaicin treatment (Cap-NC mice), and the development of spontaneous dermatitis in the Cap-NC mice was compared chronologically with that in Conv-NC mice. RESULTS: Scratching behaviour was almost completely prevented in Cap-NC mice raised for 84 days under conventional conditions, and the development of dermatitis and elevation of the serum IgE level were significantly suppressed. Histological analysis revealed that the numbers of infiltrating eosinophils and mast cells in the lesional skin of Cap-NC mice were lower than those in Conv-NC mice. Immunological studies showed that the capability of spleen T cells to produce both T-helper (Th) 1 (interferon-gamma) and Th2 [interleukin (IL)-5 and IL-13] cytokines was diminished in Cap-NC mice. Furthermore, serum levels of IL-18 were approximately twice higher in Conv-NC mice than in Cap-NC mice. CONCLUSIONS: These observations suggest that scratching behaviour contributes to the development of dermatitis by enhancing various immunological responses in the murine AD model, implying that prevention of the itch sensation and/or itch-associated scratching behaviour is an effective treatment for AD.

Animals↗

PubMed2006

COX-1 inhibition enhances scratching behaviour in NC/Nga mice with atopic dermatitis.

NC/Nga (NC) mice, spontaneously develop an eczematous atopic dermatitis (AD)-like skin lesion when kept under conventional condition (Conv), but not under specific pathogen-free (SPF) conditions, have been thought to be an animal model of AD. We have previously shown that PGD(2) and arachidonic acid inhibited the scratching behaviour of NC mice, while indomethacin enhanced it. This study was designed to assess the role of cyclooxygenase (COX)-1 and COX-2 in the itch-related scratching behaviour of NC mice. We examined the expression of COX in the skin using real-time PCR and Western blotting and the effects of SC-560 (a COX-1 selective inhibitor) or NS-398 (a COX-2 selective inhibitor) on scratching behaviour in relation to skin prostaglandin (PG) levels in NC mice. COX-1 mRNA expression was unchanged and protein expression decreased in Conv NC mice compared with that of SPF mice. By contrast, COX-2 mRNA and protein expression increased in Conv NC mice. SC-560 increased scratching behaviour and significantly reduced skin PGD(2), PGE(2) and PGF(2alpha) levels, but NS-398 did not have effects on scratching and skin PG level. Moreover, the topical application of PGD(2), which might be the endogenous inhibitor of itching, suppressed the SC-560-induced enhancement of scratching behaviour by NC mice. These results suggest COX-1-coupled skin PGD(2) biosynthesis plays a physiological role in inhibiting regulation of pruritus in NC mice with AD.

Animals↗

PubMed2006

Time course changes of scratching counts, dermatitis symptoms, and levels of cutaneous prostaglandins in NC/Nga mice.

NC/Nga (NC) mice are known to develop dermatitis resembling atopic dermatitis (AD) in conventional (Conv) conditions, but not in specific pathogen-free (SPF) conditions. We reported that the ability of skin prostaglandin D(2) (PGD(2)) production, which might be the endogenous inhibitor of itching, was attenuated in skin-lesioned Conv-NC mice. We examined the age-related change in scratching, dermatitis symptoms, and skin PGs of SPF- and Conv-NC mice. In Conv-NC, PGD(2) increased at 7 weeks, at which scratching counts increased, but dermatitis did not develop. PGE(2), PGI(2) and PGF(2alpha) increased at 10 and 13 weeks, at which dermatitis developed. The ability to produce skin PGs was examined by measuring PGs after application of arachidonic acid or after mechanical scratching using a wire brush. In Conv-NC, PGD(2) production at 13 weeks was lower than at 7 weeks. In Conv-NC, hematopoietic PGD synthase (hPGDS) expression in the skin at 13 weeks was lower than at 7 weeks by Western blotting and immunohistochemical analysis. The increase of skin PGD(2) level in the early phase of the development of dermatitis is due to the stress of extensive scratching, but did not increase in spite of the stress of extensive scratching in the late phase, due to decreasing capacity of PGD(2) production attributable to decreasing hPGDS expression in Conv-NC mice. These results suggest that a decreased ability to produce skin PGD(2) production could enhance scratching and aggravate dermatitis in Conv-NC mice.

Animals↗

PubMed2000

Fictive locomotion and scratching inhibit dorsal horn neurons receiving thin fiber afferent input.

In decerebrate paralyzed cats, we examined the effects of two central motor commands (fictive locomotion and scratching) on the discharge of dorsal horn neurons receiving input from group III and IV tibial nerve afferents. We recorded the impulse activity of 74 dorsal horn neurons, each of which received group III input from the tibial nerve. Electrical stimulation of the mesencephalic locomotor region (MLR), which evoked fictive static contraction or fictive locomotion, inhibited the discharge of 44 of the 64 dorsal horn neurons tested. The mean depth from the dorsal surface of the spinal cord of the 44 neurons whose discharge was inhibited by MLR stimulation was 1.77 +/- 0.04 mm. Fictive scratching, evoked by topical application of bicuculline to the cervical spinal cord and irritation of the ear, inhibited the discharge of 22 of the 29 dorsal horn neurons tested. Fourteen of the twenty-two neurons whose discharge was inhibited by fictive scratching were found to be inhibited by MLR stimulation as well. The mean depth from the dorsal surface of the cord of the 22 neurons whose discharge was inhibited by fictive scratching was 1.77 +/- 0.06 mm. Stimulation of the MLR or the elicitation of fictive scratching had no effect on the activity of 22 dorsal horn neurons receiving input from group III and IV tibial nerve afferents. The mean depth from the dorsal surface of the cord was 1.17 +/- 0.07 mm, a value that was significantly (P < 0.05) less than that for the neurons whose discharge was inhibited by either MLR stimulation or fictive scratching. We conclude that centrally evoked motor commands can inhibit the discharge of dorsal horn neurons receiving thin fiber input from the periphery.

Afferent Pathways↗

PubMedDate not supplied

Scratching behavior in various strains of mice.

Scratching behavior was induced in 12 strains of mice and the frequency was compared. An injection of histamine at a dose of 50 nmol induced frequent scratching behavior only in ICR mice, although the same dose of serotonin induced frequent scratching behavior in all strains of mice except for A/J. Histamine (10 nmol), serotonin (1 nmol), substance P (50 nmol) and passive cutaneous anaphylaxis induced significant vascular permeability increase in BALB/c, ICR, ddY and NC/Nga mice. These four stimuli also induced frequent scratching behavior in ICR mice. However, they failed to induce substantial increase in the incidence of scratching in the other three strains, except for ddY, which exhibited a slight but significant increase against substance P injection. These results suggest that the ICR mouse is a good responder for scratching behavior against various stimuli, especially against histamine. Thus ICR mice may be suitable for studying mediators and/or mechanisms for itching.

Animals↗

PubMed2006

Scratch lottery tickets are a poor incentive to respond to mailed questionnaires.

BACKGROUND: It has been demonstrated that the enclosure of money with a mailed questionnaire increases the response rate significantly. We evaluated scratch lottery tickets as an alternative to cash. METHODS: 1500 randomly selected Norwegians between the ages of 40 and 65 years were sent a short questionnaire. 250 received one lottery scratch ticket worth 20 Norwegian kroner (approximately 3 USD) together with the questionnaire, 250 received two scratch tickets, and 250 were promised two scratch tickets if they replied within one week. A fourth group of 250 persons received a 50 kroner banknote with the questionnaire. The remaining 500 letters served as controls. RESULTS: The overall response rate after 6 weeks was 77%. Logistic regression analysis showed that only the 50 kroner group had a response rate that was statistically significantly higher than the controls (p < 0.0001). It was also significantly higher than that in any of the other incentive groups (p < 0.0001, p < 0.004 and p < 0.0001 respectively). Female sex (p < 0.001) and age (p < 0.002) increased the response rate significantly. CONCLUSION: It is possible that the recipients scratched their cards before completing the questionnaire, and that it was a disincentive for the majority that they did not win anything. Lottery scratch tickets are no substitute for cash as an incentive to respond to a questionnaire.

Adult↗

PubMed2005

Antipruritic effect of ginsenoside rb1 and compound k in scratching behavior mouse models.

The antipruritic and vascular permeability-inhibitory effects of ginsenoside Rb1, a main component of ginseng frequently used as a traditional medicine in Asian countries, and its metabolite compound K by intestinal microflora were investigated in scratching behavior animal models induced by compound 48/80, substance P, and histamine. Ginsenoside Rb1 and compound K orally administered 1 and 6 h before the treatment of compound 48/80 showed antipruritic effect. These ginsenosides administered at a dose of 50 mg/kg 6 h before the treatment of compound 48/80 inhibited scratching behaviors by 51% and 64%, respectively, compared with that of the control. These ginsenosides also inhibited the vascular permeability of skin. Compound K intraperitoneally administered 1 h before the treatment of compound 48/80 potently inhibited the scratching behaviors induced by compound 48/80. However, intraperitoneally administered ginsenoside Rb1 did not inhibit scratching behaviors. Compound K inhibited compound 48/80-, substance P-, and histamine-induced scratching behaviors, with 50% inhibitory doses of 4.2, 5.9, and 3.8 mg/kg, respectively, and vascular permeability, with 50% inhibitory doses of 5.8, 6.8, and 4.1 mg/kg, respectively. These results suggest that ginsenoside Rb1 and its metabolite compound K by intestinal microflora can improve scratching behaviors.

Animals↗

PubMed2003

Three-dimensional image construction by curved surface scratches.

Scratches on the surface of transparent or nontransparent media reflect, refract, or diffract incident light. Under parallel illumination each length element of a scratch produces a fan beam (in the absence of diffuse scattering). Looking at a curved scratch, the right and left eyes are hit by different fan beams. Thus each eye sees a separate light spot on the scratch, which is the origin of the fan beam. In certain circumstances these spots can be stereoscopically combined by both eyes and only one light spot in space is seen. Three-dimensional images can be created by a large number of such spots originating from circular or semicircular scratches. These scratches can easily be produced on the surface of Plexiglas or other materials by using a compass. Some experiments and the theory of the so-called scratchograms are given. A comparison with holographic images is made.

Journal Article↗

PubMed2003

In vivo sensitivity of human root dentin to air blast and scratching.

BACKGROUND: The present study evaluated the prevalence of radicular sensitivity to scratching as well as the effects of a common oxalate desensitizing agent on sensitivity to air blast and scratching. METHODS: Eighty-seven patients self-reporting dentin hypersensitivity, with at least two hypersensitive teeth, were included. Prior to any treatment, their sensitivity to air blast was recorded and rated as absent or present, and the force necessary to trigger pain when scratching was measured with a scratchometer in cN. For each patient one sensitive tooth was treated with an oxalate desensitizing agent and the other one with a placebo solution. The same measurements were carried out after treatment. RESULTS: Following treatment with a placebo solution, 70% of the teeth remained sensitive to air blast while only 38% of the desensitizing agent-treated teeth remained sensitive to air blast (P < 0.01). The mean force required to elicit pain prior to any treatment was 44 +/- 17 cN. This force statistically increased significantly after application of the placebo (53 +/- 17 cN) (P < 0.05). After using the desensitizing agent, the force was even higher (95 +/- 24 cN) (P < 0.01). Only 8% of the teeth treated with the desensitizing agent did not respond to treatment compared to 37% of the teeth treated with the placebo solution. CONCLUSIONS: The placebo solution had a significant effect on sensitivity to air blast and to scratching (P < 0.05). The oxalate desensitizing agent was more effective than the placebo solution at decreasing the sensitivity both to air blast and to scratching (P < 0.01). The sensitivity to air blast seems to be overestimated because, after using the desensitizing agent, 38% of the teeth remained sensitive to air blast but only 8% remained sensitive to scratching. Pulpal inflammation may be involved in those teeth that did not respond to treatment.

Adolescent↗

PubMed1981

[Activity of interneurons of the lumbosacral division of the spinal cord during fictive scratching].

Impulse activity of lumbosacral interneurons was recorded extracellularly during fictitious scratching in decerebrated immobilized cats. Most neurons whose activity was modulated during fictitious scratching were revealed in the lateral intermediate zone and in the lateral ventral horn. These neurons were divided into some groups differing in the type of activity modulation during fictitious scratching. Neurons whose activity did not change during fictitious scratching were mainly located dorsally in the gray matter. Cells showing wide convergence of excitatory influences from high threshold cutaneous and muscle afferents referred mainly to "aiming" neurons. In contrast to "aiming" neurons, most cells with inputs from only low threshold cutaneous or high threshold muscle afferents belonged to "scratching" neurons. The neuronal activity in different groups is shown to depend on the limb position. The neuronal organization of the spinal scratching generator is discussed on the basis of the obtained data.

Animals↗