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PubMed1992

Peripheral 5-carboxamidotryptamine induces hindlimb scratching by stimulating 5-HT1A receptors in rats.

Treatment of rats with 5-carboxamidotryptamine (5-CT) or 5-methoxy-tryptamine (5-MeOT) induces a hindlimb scratch response. These compounds have high affinity for 5-HT1A and 5-HT1D receptors. The selective 5-HT1A receptor agonist N,N-dipropyl-5-CT (DP-5-CT) also induced hindlimb scratching while the selective 5-HT1D receptor agonist, sumatriptan, did not. 5-CT-induced hindlimb scratching was inhibited dose-dependently by several 5-HT1A antagonists (BMY 7378, NAN-190, MDL 73005EF and pindobind-5-HT1A) as well as the non-selective 5-HT antagonist, methiothepin. Pretreatment of rats with the serotonin (5-HT) synthesis inhibitor, p-chlorophenylalanine (PCPA) or the 5-HT depleting agent, reserpine, markedly attenuated 5-CT-induced hindlimb scratching. These data suggest that hindlimb scratching induced by 5-HT agonists may not be centrally mediated but rather may be mediated by a neuronal 5-HT1A receptor localized outside the blood-brain barrier.

5-Methoxytryptamine↗

PubMed1993

Possible involvement of the spinal substance P system in pilocarpine-induced scratching in mice.

IT administration of pilocarpine in the spinal subarachnoid space of mice produced a dose-related hindlimb scratching. When coadministered with substance P IT, the pilocarpine-induced scratches were enhanced by high doses of substance P but not by subthreshold doses. This characteristic behavioral response was inhibited dose dependently by IT coadministration of spantide [D-Arg1, D-Trp7,9,Leu11] substance P. Significant antagonistic effects of [D-Phe7,D-His9] substance P (6-11), a selective antagonist for substance P receptors, and substance P (1-7), a substance P N-terminal fragment, were observed against the pilocarpine-induced scratching. Pretreatment with substance P antiserum resulted in the reduction of the response to pilocarpine. When coadministered IT with pilocarpine, atropine potently inhibited pilocarpine-induced scratching. These results demonstrate that not only muscarinic receptors but also substance P-containing neurons in the mouse spinal cord may be involved in elicitation of the scratching behavior following IT injection of pilocarpine.

Afferent Pathways↗

PubMedDate not supplied

Characterization of intrathecal vasopressin-induced antinociception, scratching behavior, and motor suppression.

Intrathecal (IT) administration of vasopressin produces antinociception, scratching behavior, and motor suppression. The present experiments characterized these effects with regards to the following: 1) VP receptor specificity, 2) possible involvement of endogenous opiates, 3) possible involvement of seizure activity, and 4) whether the antinociception is due to direct actions of VP at the spinal cord. These studies showed that IT administration of a V1-specific vasopressin antagonist completely blocked the antinociception, scratching behavior, and motor suppression produced by 25 ng IT vasopressin. Furthermore, IT administration of the vasopressin metabolite, [pGlu4,Cyt6]AVP(4-9), produced none of the effects produced by vasopressin. Systemic administration of the opiate antagonists naloxone (1 mg/kg IP) and naltrexone (10 mg/kg IP) had no significant effect on the antinociception produced by IT vasopressin, whereas naltrexone potentiated the scratching behavior. Neither the IT vasopressin-induced antinociception nor scratching behavior was affected by pretreatment with the anticonvulsant sodium valproate. In addition, IT vasopressin inhibited the tail flick reflex in rats with transected spinal cords, demonstrating direct spinal effects of vasopressin. In conclusion, IT administration of vasopressin produces antinociception, scratching behavior, and motor suppression via activation of VP-specific receptors in the spinal cord.

Animals↗

PubMed1987

Scratching behaviour in arthritic rats: a sign of chronic pain or itch?

In a previous study, it was shown that adjuvant-induced arthritic rats present an abnormal behaviour pattern up to 60 days after inoculation with Mycobacterium butyricum. The purpose of the present study was to investigate how long the abnormal behaviour pattern continues, and whether the observed increased scratching behaviour is a parameter of chronic pain or rather a reaction to itch. Adjuvant-induced arthritic rats were observed for up to 180 days after the inoculation and their behaviour was quantitatively analysed. The following behavioural changes persisted for more than 60 days: rearing, running and climbing were decreased while grooming, scratching, biting and freezing were increased. No behavioural changes were observed 120 days after the inoculation. The increased scratching was not influenced by an antihistamine drug (astemizole). Not only morphine but also acetylsalicylate selectively depressed the increased scratching behaviour without influencing the other behaviours. These results reinforce the notion that in arthritic rats the increased scratching is a sign of chronic pain.

Animals↗

PubMed2005

The effects of olopatadine hydrochloride on the number of scratching induced by repeated application of oxazolone in mice.

It is suggested that atopic dermatitis is a skin disease associated with itching as subjective symptoms, and histamine H(1) receptor antagonists are used in order to prevent the itching, and the deterioration for scratch by itching. Histamine H(1) receptor selective anti-histamine olopatadine hydrochloride (olopatadine; Allelock shows consistent efficacy and safety in the treatment of allergic disorders. We investigated the possible efficacy of olopatadine on the number of scratching induced by repeated application of oxazolone in BALB/c mice. The repeated treatment of olopatadine significantly inhibited the ear swelling and the increased number of scratching. It significantly inhibited the increased production of interleukin (IL)-4, IL-1beta and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the lesioned ear. Moreover, it significantly inhibited the increased production of nerve growth factor (NGF) and substance P. On the other hand, loratadine, bepotastine and chlorpheniramine did not inhibit the ear swelling and the increased number of scratching. These results indicate that olopatadine inhibited not only the increased production of cytokines but also NGF and substance P unlike other histamine H(1) receptor antagonists. It was suggested that olopatadine suppressed the increased number of scratching by the anti-inflammatory effects. Therefore, olopatadine appears to exert additional biological effects besides its blockade of a histamine H(1) receptor.

Animals↗

PubMed2006

Inhibition of scratching behavior associated with allergic dermatitis in mice by tacrolimus, but not by dexamethasone.

Itching is the most important problem in many allergic and inflammatory skin diseases especially in atopic dermatitis. However, animal models for allergic dermatitis useful for the study of itching have rarely been established. We established a mouse allergic dermatitis model involving frequent scratching behavior by repeated painting with 2,4-dinitrofluorobenzene (DNFB) acetone solution onto the mouse skin, and comparatively examined the effects of tacrolimus and dexamethasone on the dermatitis and associated scratching behavior. Repeated DNFB painting caused typical dermatitis accompanied by elevated serum immunoglobulin E (IgE) and frequent scratching behavior. An apparent thickening of the epidermis and dermis, and the significant accumulation of inflammatory cells were observed. Increased interferon (IFN)-gamma mRNA expression and the induction of interleukin (IL)-4 and IL-5 mRNA expression were also observed in the skin lesion. The scratching behavior was inhibited by dibucaine and naloxone. Although tacrolimus reduced the increased expression of IFN-gamma and IL-4 mRNA, dexamethasone potently depressed that of IFN-gamma, IL-4 and IL-5 mRNA. Dexamethasone inhibited the accumulation of lymphocytes and eosinophils, although tacrolimus did not. Both drugs failed to inhibit the elevation of serum IgE levels. Tacrolimus significantly inhibited the scratching behavior that was associated with the inhibition of nerve fiber extension into the epidermis, whereas dexamethasone failed to have any effect. The mouse dermatitis model seems to be beneficial for the study of itching associated with allergic dermatitis, such as atopic dermatitis, and tacrolimus seems to exhibit an anti-itch effect through the inhibition of nerve fiber extension at least in part.

Allergens↗

PubMed2003

Dentin deformation after scratching with clinically-relevant forces.

OBJECTIVE: In order to understand the mechanism of dentin sensitivity to tactile stimuli, the purpose of this study was to evaluate possible permanent deformation of dentin produced by scratching dentin surfaces with clinically-relevant forces. METHODS: Midcoronal dentin was prepared from twenty human teeth and polished to 4000-grit and ultrasonicated. The dentin surface of each specimen was scratched under forces ranging from 30 to 100 centi-Newtons (cN). The depth of the grooves were measured with a profilometer and the overall hardness of dentin in the vicinity of the grooves was measured. Additional dentin specimens were prepared for SEM evaluation. RESULTS: Dentin hardness was constant and no statistical difference was found among the specimens. Statistically significant differences in groove width and depth were found when increasing force was applied to the dental explorer tip. The depth of the groove ranged from 0.21+/-0.09 microm for the 30 cN group to 1.27+/-0.39 microm for the 100 cN group. The width of the groove ranged from 19.3+/-4.0 microm for the 30 cN group to 43.0 microm for the 10 0 cN group. CONCLUSIONS: (1). The threshold force necessary to create scratches in dentin with a dental explorer was 30 cN or a compressive stress of 1003 MPa. As this exceeds the crushing strength of dentin, this force produces plastic deformation of dentin; (2). Theoretical calculations indicated that even the highest scratching forces (100 cN) could not induce sufficient fluid flow to activate pulpal mechanoreceptors, although it could induce sufficient elastic deformation to theoretically shift dentinal fluid at a rate sufficient to activate mechanoreceptors; (3). The results of this work may lend support the hydrodynamic theory in that scratching of dentin surfaces causes both elastic and plastic deformation of dentin that may displace dentinal fluid toward the pulp where it could activate mechanoreceptors.

Dentin↗

PubMed2002

Possible role of mast cells in cineole-induced scratching behavior in mice.

We examined the scratch (itch) inducing effect of 1,8-cineole (cineole), a monoterpene oxide present in many plant essential oils and the possible role of mast cells in the response. Subcutaneous injection of cineole (10, 20 and 40 microl/site) or the mast cell degranulating agent, compound 48/80 (25, 50 and 100 microg/site) into the rostral back of mice induced a scratching behavior. This response of cineole as well as that of 48/80 was markedly suppressed in mice subjected to mast cell desensitization by repeated injections of 48/80. The cineole-induced scratching was also significantly diminished in animals pretreated with diphenhydramine, the histamine H1-receptor antagonist or cyproheptadine, the dual histamine/serotonin-receptor antagonist. Furthermore, the scratch-inducing effect of cineole was greatly reduced in mice that received the opioid antagonist naloxone or the selective adenosine A1-receptor agonist, N6-cyclopentyladenosine (CPA), but not the more selective adenosine A2-receptor agonist, 5'-N-ethylcarboxamidoadenosine (NECA). The data suggest a likely role for mast cells in cineole-induced scratching behavior of mice, possibly involving adenosinergic and opioidergic mechanisms.

Adenosine↗

PubMed2003

Deletion of the preprotachykinin A gene in mice does not reduce scratching behavior elicited by intradermal serotonin.

Itch is thought to be signaled by a sub-population of pruritogen-selective C-fiber primary afferents. To assess a possible role of the neuropeptide, substance P (SP), in the central neurotransmission of itch, we investigated itch-related scratching behavior elicited by intradermal injection of serotonin (5-HT; 0.03-0.3%) in normal mice (wildtype, WT) and knockout mice (KO) with deletion of the preprotachykinin A gene. Both KO and WT groups showed dose-related increases in the number of 5-HT-evoked scratching bouts over the 44 min observation period. There were no significant differences in the numbers or durations of scratching bouts between WT and KO groups, although KO mice exhibited numerically more spontaneous and 5-HT-evoked scratching. It is concluded that either SP is not involved in the central neurotransmission of itch-related scratching behavior in this strain of mouse, or that compensatory developmental changes in the KO mice allow itch-related signaling.

Animals↗

PubMedDate not supplied

An automated method for registering and quantifying scratching activity in mice: use for drug evaluation.

A method, which allows the automated registration of the scratching activity of the hind legs of a mouse for periods longer than 24 h, has been developed and validated. Aluminium rings are placed around the hind limbs of mice just above the ankle. Mice are housed individually in cages placed on the scratch detection unit (SDU), which contains ferrite rods fitted with copper coils. The movement of the metal rings in the field generated by the coils elicits a signal that can be transformed into peaks of different frequencies. Scratching was defined as a regular waveform with a frequency of > 15 Hz and with an amplitude of < 200 mV. Quantification of spontaneous scratching by chronic proliferative dermatitis mice or histamine and Compound 48/80-treated C57BL/Ka mice was performed visually (using a video recording showing both the mice and the computer-generated signal) and using the pruritus detection system (PDS = SDU plus computer program). The correlation between visual and automatic quantification of spontaneous cpdm mouse scratching was 81.7+/-2.5% (mean +/- S.E.M.). For histamine, the correlation was 85.6+/-3.6% (mean +/- S.E.M.) and for Compound 48/80, 85.8+/-3.1% (mean +/- S.E.M.). The PDS routinely detected less than 5% false-positive signals.

Animals↗

PubMed2006

Lateralized scratching in chimpanzees (Pan troglodytes): Evidence of a functional asymmetry during arousal.

This study evaluated laterality in scratching by chimpanzees (n = 89) during socially arousing circumstances. Hand use and the side of the body scratched was recorded during a baseline and experimental condition. In the experimental condition, chimpanzees were shown a video of other conspecifics sharing, fighting over, and consuming a watermelon. Self-touches were categorized as either rubs or scratches. The chimpanzees showed a significant right hand bias for rubbing and also significantly directed the rubs to the right side of the body. For scratching, the chimpanzees showed no hand preference but a significant bias for scratching on the left side of the body. These results support the view that the right hemisphere regulates the autonomic nervous system during arousal.

Animals↗

PubMedDate not supplied

Scratch induction in the rat by intradermal serotonin: a model for pruritus.

Eight substances (histamine, compound 48/80, kallikrein, trypsin, papain, substance P, serotonin and platelet activating factor) were injected intradermally (volume 50 microl) into the rostral back (neck) of rats in order to establish an animal model for peripherally elicited pruritus. While serotonin induced excessive scratching at the site of injection, the other substances were weak or inactive. The dose-response relationship of serotonin was sigmoid, EC50=2.1 mg/ml (95% confidence interval: 1.0 to 4.3 mg/ml). Injections of serotonin 1 mg/ml into the caudal back elicited no scratching at all, i.e. neither at the site of injection nor elsewhere, so the experiment indicated no systemic effect of serotonin 1 mg/ml intradermally. Scratching was probably elicited histamine-independently, since histamine itself did not elicit scratching. The intra- and inter-observer variations were 3-4%. We conclude that serotonin is a reproducible local pruritogen eliciting scratching in the rat. The model may be useful in research and development of topical antipruritics of the nonhistaminic type as well as for various other purposes in pruritus research.

Animals↗

PubMed2006

Sleep disturbance in patients with lichen simplex chronicus and its relationship to nocturnal scratching: A case control study.

BACKGROUND: Lichen simplex chronicus (LSC) is a common pruritic disorder resulting from repeated rubbing and scratching. Nighttime pruritus is a common feature in LSC and may disrupt the sleep pattern. The aim of this study is to determine whether there are sleep abnormalities in patients with LSC. PATIENTS AND METHODS: Fifteen patients with LSC and 15 age-, sex- and body mass index-matched control subjects were enrolled in the study. No participant had any other medical or psychiatric illness. All subjects were evaluated by overnight polysomnography, scratch electrodes, Epworth sleepiness scale and a general questionnaire for demographic data and sleep problems. RESULTS: There were no significant differences in the groups for total sleep time, sleep efficiency, sleep latency, rapid eye movement (REM) latency, percentage of stage 1 non-REM sleep and REM sleep. The percentage of stage 2 non-REM sleep was higher (P < 0.05) and the percentage of slow wave sleep (stages 3 and 4) was lower in the study group (P < 0.05) than in the controls. The patient group had a mean of 15.9 +/- 7.5 arousal index and 22.8 +/- 14.1 awakenings compared with 9.5 +/- 3.1 and 10.4 +/- 3.9, respectively, in the controls (P < 0.05, P < 0.01, respectively). Arousals of patients were mainly observed in non-REM sleep. The number of scratching bouts ranged from 6 to 20 per night. Scratching episodes were observed frequently during stage 2 non-REM sleep. CONCLUSION: Polysomnographic findings of patients with LSC demonstrated that sleep structure is disturbed by arousals and awakenings related to scratching bouts during sleep.

Adult↗

PubMed2004

A generalized model for scratch detection.

This paper presents a generalization of Kokaram's model for scratch lines detection on digital film materials. It is based on the assumption that scratch is not purely additive on a given image but shows also a destroying effect. This result allows us to design a more efficacious scratch detector which performs on a hierarchical representation of a degraded image, i.e., on its cross section local extrema. Thanks to Weber's law, the proposed detector even works well on slight scratches resulting completely automatic, except for the scratch color (black or white). The experimental results show that the proposed detector works better in terms of good detection and false alarms rejection with a lower computing time.

Algorithms↗

PubMed2005

Inhibition of scratching behaviour caused by contact dermatitis in histidine decarboxylase gene knockout mice.

A neuronal system dedicated to itch consists of primary afferent and spinothalamic projection neurons. Histamine is thought to be one of the main mediators for the transmission of itch sensation. However, there are little available information on the role of histamine in scratching behaviour and sensory transmission of atopic dermatitis and chronic eczema. In the present study, the role of histamine in scratching behaviour and neural conduction of sensation in the chronic eczema model was investigated by using l-histidine decarboxylase (HDC) gene knockout mice lacking histamine. The chronic contact dermatitis was induced with daily application of diphenylcyclopropenone (DCP) on a hind paw of HDC (+/+) and HDC (-/-) mice for 2 months. The observation of scratching behaviour and the hot-plate test were performed in both mice. Histological studies were performed in the skin and spinal cord tissues. Histological examination revealed that both HDC (+/+) and HDC (-/-) mice displayed the similar extent of inflammatory cell infiltration, hyperplastic epidermis and newly spreading of neuronal processes in the skin tissue. Scratching behaviour was exclusively induced in HDC (+/+) mice, whereas it was barely observed in HDC (-/-) mice. The expression of c-Fos was specifically upregulated in HDC (+/+) mice in lamina I of the spinal dorsal horn following repeated DCP application. Scratching behaviour in chronic contact dermatitis in mice was thought mainly mediated with histamine. The afferent pathway of sensation in chronic contact dermatitis model may connect with the central nervous system through lamina I of the spinal dorsal horn.

Animals↗

PubMed2004

Effects of tacrolimus ointment on facial eruption, itch, and scratching in patients with atopic dermatitis.

The action of tacrolimus ointment on pruritus in atopic dermatitis is still unclear. In this open study we investigated both the relationship between the severity of eruptions and the degree of itch and scratching in patients with atopic dermatitis and the effects of topical tacrolimus on these symptoms. Seventy adults with moderate to severe atopic dermatitis with facial eruptions that were recalcitrant to topical steroids applied a 0.1% tacrolimus ointment twice per day after discontinuation of topical steroid. The eruption scores and an assessment of the itch and scratching were recorded for 12 weeks. Oral antihistamine was prescribed at least one month before the study and continued unchanged during the study in each patient. The percentage reduction in the score of itch and scratching after two weeks (n=59) was significantly higher than in the score of eruption. Although there was no significant relationship between the severity of the eruptions and the degree of itch and scratching during steroid application, a relationship became significant after four weeks (n=59) of tacrolimus use by a one-factor ANOVA analysis. This suggests that tacrolimus ointment is effective for the itch and scratching in cases where degrees might be discrepant from the severity of eruptions in patients with recalcitrant facial eruptions of AD.

Administration, Topical↗

PubMed1991

Nocturnal scratching and its relationship to the disturbed sleep of itchy subjects.

This study of the relationship between nocturnal scratching and sleep is based on an analysis of 17 overnight polygraphic records of the scratch bouts and EEG of severely itchy patients. Our patients spent little time in deep orthodox sleep (stages 3 and 4), which was absent from 7 of the 17 records. Bouts of scratching were found to occur in all stages of sleep but were most numerous in stage 1 (light orthodox sleep). Sleep tended to remain stable, i.e. in a single sleep stage, for the 40 s immediately before a bout of scratching but had often changed to a more superficial stage by the time the bout had ceased, implying perhaps that scratching itself was the event linked most closely with arousal.

Adolescent↗

PubMed2005

Increased scratching counts depend on a decrease in ability of cutaneous prostaglandin D2 biosynthesis in NC/Nga mice with atopic dermatitis.

Spontaneous and 2,4,6-trinitrochlorobenzene (TNCB)-induced dermatitis models using NC/Nga mice have been recognized as animal models of atopic dermatitis. We reported that scratching behavior leads to dermatitis in a spontaneous dermatitis but not in a TNCB-induced dermatitis. Prostaglandin D2 (PGD2) suppressed the scratching behavior of NC/Nga mice, suggesting that PGD2 plays a physiological role on inhibiting pruritus. We studied whether there was a difference in skin PG contents between spontaneous and TNCB-induced dermatitis. Spontaneous dermatitis was induced by cohabitation with NC/Nga mice having severe skin lesions. TNCB-induced dermatitis was caused by applications of TNCB. PGD2, PGE2, 6keto-PGF1alpha, and PGF2alpha contents in the skin were examined using enzyme-immunoassay kits. For studying ability to produce skin PGs, PG contents were evaluated after topical treatment of arachidonic acid (AA) or mechanical scratching. In spontaneous dermatitis, PGE2, 6keto-PGF1alpha, and PGF2alpha contents increased with dermatitis, but only PGD2 did not do so. In TNCB-induced dermatitis, PGD2, PGE2, 6keto-PGF1alpha, and PGF2alpha increased. Determination of skin PG contents after AA treatment or mechanical scratching revealed that skin PGD2 production of conventional group of spontaneous dermatitis was lower than the specific pathogen-free group. It seemed that ability of skin PGD2 production was attenuated in spontaneous dermatitis. These results suggest that enhancement of scratching behavior in spontaneous dermatitis was caused by the defect of ability to produce PGD2, which plays a physiological role in inhibiting pruritus, resulting in development of dermatitis.

Administration, Topical↗