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Some observations on the direction of scratch marks.

This study consists of two parts. In the first we recorded 1696 scratch marks seen on 69 pruritic patients. The scratch marks followed a consistent pattern on the skin, which was independent of the cause of the itching. The most striking feature was a longitudinal alignment on the limbs. Next we tried to relate our findings to experimental work that suggests that itching is extinguished most effectively by counterstimuli applied within the same dermatomal segment. If this is the case, sufferers from itchy skin diseases might be expected to scratch itchy points on their skin using strokes directed along dermatomal lines, thereby gaining maximal relief. We used the data obtained during the first part of our study to test this possibility. Fifty-one percent of the scratch marks analyzed ran at an angle of less than 20 degrees to the nearest interdermatomal line (significantly higher than the 22.5% expected by chance). However the tendency for scratch marks to run along dermatomal lines was confined to the limbs. In addition, the preferred scratch directions of a group of nonitchy subjects, not driven by the need to alleviate actual itching, coincided closely with the pattern of scratch marks seen on the itchy patients. The direction of scratch marks may therefore be determined as much by mechanical factors affecting the ease of scratching as by the distribution of dermatomes.

Adolescent↗

Effects of nitrazepam on nocturnal scratching in adults with atopic dermatitis: a double-blind placebo-controlled crossover study.

We investigated the effect of nitrazepam on nocturnal scratching in 10 adult out-patients with atopic dermatitis (AD) using a double-blind placebo-controlled crossover method. Patients were given either nitrazepam (Benzalin tablets containing 5 mg nitrazepam) or a placebo on 3 successive nights, with a washout interval of 4 days. We used an infrared video camera to identify bouts of scratching lasting more than 5 s. These were counted and the duration of all the bouts of scratching (total scratching time, TST) was calculated. The percentage of TST to total recording time (TST%) was used as an index of nocturnal scratching. The frequency with which bouts of scratching (bouts/h) occurred was reduced by 10 mg nitrazepam (7.7 +/- 3.6 with nitrazepam vs. 9.6 +/- 3.6 with placebo, P < 0.05). However, the mean duration (s/bout) of the bouts of scratching was longer with 10 mg nitrazepam (32.3 +/- 23.4 with nitrazepam vs. 19.1 +/- 10.0 with placebo, P < 0.05). As a result, there was no significant difference between TST% (6.5 +/- 4.2 with nitrazepam vs. 5.4 +/- 3.8 with placebo, not significant). All the above values are mean +/- SD. The degree of itching and the condition of the AD did not change during the 2 weeks of the study. We conclude that taking 10 mg nitrazepam is not an effective way of reducing the total duration of nocturnal scratching in AD patients, although it decreases the frequency with which bouts of nocturnal scratching occur.

Adolescent↗

Involvement of histamine H3 receptors in scratching behaviour in mast cell-deficient mice.

BACKGROUND: Although the roles of histamine H3 receptors have been studied in several tissues such as the brain, lung, spleen, colon and peripheral sensory nerve endings, the involvement of H3 receptors in skin responses particularly in relation to scratching behaviour are not well documented. OBJECTIVES: This work was performed to study the effects of histamine H3 antagonists on scratching behaviour in mast cell-deficient mice. METHODS: Histamine H3 antagonists iodophenpropit and clobenpropit, histamine and substance P were injected intradermally into the rostral part of the back of mast cell-deficient (WBB6F1 W/Wv) and wild-type (WBB6F1+/+) mice and scratching behaviour was measured for 60 min. The effects of H1 antagonists on scratching behaviour induced by H3 antagonists were also investigated. RESULTS: Intradermal injection of iodophenpropit and clobenpropit at doses of 10 and 100 nmol per site caused significant increases in scratching behaviour in both mast cell-deficient and wild-type mice. Histamine also caused a dose-related increase in the incidence of scratching behaviour, and a significant effect was observed at a dose of 100 nmol per site in both mast cell-deficient and wild-type mice. Substance P was also effective in causing scratching behaviour in both mast cell-deficient and wild-type mice. However, histamine H1 antagonists diphenhydramine and chlorphenamine failed to inhibit H3 antagonist-induced scratching behaviour in both types of mice. CONCLUSIONS: Our results indicated that intradermal injection of H3 antagonists induces scratching behaviour and that chemical mediators other than histamine seem to be involved in the response.

Animals↗

Responses of superficial dorsal horn neurons to intradermal serotonin and other irritants: comparison with scratching behavior.

Scratching behavior is used to assess itch sensation in animals, but few studies have addressed the relative scratch-inducing capacity of different algesic and pruritic chemicals. Furthermore, central neural mechanisms underlying itch are not well understood. We used electrophysiological and behavioral methods to investigate the ability of several irritant chemicals to excite neurons in the superficial dorsal horn, as well as to elicit scratching, in rats. In anesthetized rats, single neurons in the superficial lumbar dorsal horn, identified by their responsiveness to intracutaneous (ic) histamine, were classified as wide dynamic range (WDR) or nociceptive-specific (NS). Serotonin (5-HT) given ic to the paw excited most (88%) WDR and NS neurons over a prolonged time course (often up to 40 min). 5-HT-evoked responses exhibited significant tachyphylaxis. Most neurons also gave shorter-duration responses to ic capsaicin (92%) and mustard oil (71%). In separate behavioral experiments, significant dose-related hind limb scratching directed at the ic injection site in the back of the neck was elicited by 5-HT over a time course similar to that of evoked neuronal firing. A second 5-HT injection made 40 min later at the same site elicited significantly less scratching. Formalin also elicited scratching that was not dose-related and less than that evoked by 5-HT. 5-HT and Formalin also evoked head or whole-body shakes that were significantly correlated with scratching. Neither histamine, capsaicin, nor vehicle controls elicited significant scratching or shaking. In rats, 5-HT appears to be more pruritogenic than histamine as assessed by scratching and shaking behavior, and excites superficial dorsal horn neurons over a behaviorally relevant time course. However, because most neurons additionally responded to pain-producing stimuli, they are not itch-specific. They might nonetheless contribute to neural pathways that distinguish between pain and itch based on some neural mechanism such as frequency coding.

Animals↗

Evaluation and characterization of mouse scratching behavior by a new apparatus, MicroAct.

We evaluated and characterized the mouse scratching behavior using a new apparatus, MicroAct. Scratching behavior was evoked in ICR and BALB/c mice by compound 48/80, passive cutaneous anaphylaxis or repeated hapten application. Under the present experimental condition, MicroAct detected consecutive scratching behavior (events) consisting of 3 or more beats. Although the detecting standard of MicroAct was not identical to that of an observer, the number of events detected by MicroAct and by an observer were almost comparable with each other. Frequency of events, total scratching time and total number of beats detected by MicroAct increased depending on the intensity of the causing stimuli for scratching. In contrast, the duration of each event and the number of beats in each event increased only slightly, but the scratching speed was almost constant. The present results demonstrate that MicroAct is a useful tool for evaluating mouse scratching behavior. Mouse scratching behavior seems to have a relatively fixed pattern and the causing stimulus increases mainly in the frequency of event without affecting the scratching speed.

Animals↗

Interruptions of fictive scratch motor rhythms by activation of cutaneous flexion reflex afferents in the turtle.

A low-spinal immobilized turtle displays a fictive scratch reflex in hindlimb muscle nerves in response to mechanical stimulation of specific regions of the shell (Robertson et al., 1985). There are 3 forms of the scratch reflex: the rostral, the pocket, and the caudal; each exhibits rhythmic activation of hindlimb motor neurons. Cutaneous stimulation of the distal hindlimb elicits a fictive flexion reflex that exhibits tonic excitation of hip protractor (flexor) motor neurons and tonic inhibition of knee extensor motor neurons (Stein et al., 1982). In the present study, we describe the motor pattern blends that resulted from transient activation of either the ipsilateral or the contralateral flexion reflex pathway during ongoing scratch motor patterns. Two types of blends were observed: (1) insertions of a flexion reflex synergy into an interrupted scratch cycle and (2) deletions of parts of a scratch cycle. Associated with each type of motor pattern blend was a permanent reset of the ongoing scratch rhythm. The sign of the reset (phase-advance or phase-delay) could be predicted for all forms of the scratch based on the location of the foot stimulus (ipsi- or contralateral) and its timing relative to the hip protractor/retractor cycle. The timing of knee extensor activity within the hip cycle is different for each form of the scratch (Robertson et al., 1985); thus, the sign of the reset cannot be predicted from the timing of the stimulus relative to the knee extensor cycle. These results indicate the importance of the hip rhythm in determining the overall timing of the scratch reflex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Blends of rostral and caudal scratch reflex motor patterns elicited by simultaneous stimulation of two sites in the spinal turtle.

Simultaneous tactile stimulation of 2 sites on the body surface of a spinal turtle elicits complex blends of the scratch forms and motor patterns associated with each site. Our previous work has utilized 1-site stimulation to elicit distinct forms of the scratch reflex in the spinal turtle (Mortin et al., 1985; Robertson et al., 1985). Using this paradigm, stimulation of a site on the shell bridge anterior to the hindlimb elicits a rostral scratch reflex in which the dorsum of the foot rubs against the stimulated site; stimulation of a site near the tail elicits a caudal scratch reflex in which the heel or side of the foot rubs against the stimulated site (Mortin et al., 1985). During each scratch cycle, the monoarticular knee extensor muscle is active when the limb rubs against the stimulated site, and there is rhythmic alternation between hip protractor and hip retractor muscle activity (Robertson et al., 1985). In a rostral scratch, the monoarticular knee extensor muscle is active during the latter portion of hip protractor muscle activity; in a caudal scratch, the monoarticular knee extensor muscle is active near the end of hip retractor muscle activity. Pure-form motor patterns that are similar to those recorded from these muscles during movement can be recorded from the corresponding nerves in a spinal turtle immobilized with a neuromuscular blocking agent (Robertson et al., 1985). In this paper, we describe blend responses to simultaneous stimulation of 2 sites, one in the rostral scratch and the other in the caudal scratch receptive field. During these blends, the responding hindlimb rubs against both stimulated sites in one continuous movement sequence.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Pharmacological analysis of the scratching produced by dopamine D2 agonists in squirrel monkeys.

Several dopamine agonists, administered i.m., produced persistent, excessive and non-localized scratching in squirrel monkeys (Saimiri sciureus). Studies were conducted with a series of drugs to determine the pharmacological mechanisms responsible for this effect. All of the dopamine D2 agonists studied produced dose-related increases in scratching, whereas several dopamine D1 receptor agonists, indirect dopamine agonists and drugs acting on other receptors failed to produce dose-related increases in scratching. The scratching produced by D2 agonists was stereospecific; (-)-NPA produced scratching whereas its (+)-enantiomer was inactive up to doses 300-fold higher. Scratching induced by quinpirole was attenuated by both D2 and D1 antagonists, and this antagonism was stereospecific, with the D2 antagonist (-)-eticlopride, but not its enantiomer, active. Sensitivity developed to the effects of D2 agonists with the quinpirole dose-effect curve shifting to the left by a factor of approximately 64. Two partial D2 receptor agonists (SDZ 208-911 and SDZ 208-912) had limited efficacy in producing scratching, however, one partial D2 receptor agonist (terguride) was fully efficacious, suggesting that there are spare receptors for this effect. The peripherally active dopamine antagonist domperidone and the histamine antagonist diphenhydramine also reduced the scratching induced by D2 agonists, but not to the same extent as centrally acting D2 antagonists. Scratching in squirrel monkeys is an effect that appears to be due to agonist actions at D2 receptors, and may be mediated by a release of histamine. This behavioral activity may be useful as an in vivo indication of D2 receptor activity in primates.

Animals↗

Glycinergic inhibition contributes to the generation of rostral scratch motor patterns in the turtle spinal cord.

Cutaneous stimulation within the rostral scratch receptive field in a low spinal-immobilized turtle elicits a fictive rostral scratch reflex characterized by robust rhythmic motor output from ipsilateral hindlimb muscle nerves and weaker, alternating motor discharge in contralateral nerves. Simultaneous bilateral stimulation elicits bilateral rostral scratch motor patterns in which activity on the right and left sides alternates. We investigated the role of glycinergic inhibition in the generation and coordination of fictive rostral scratch motor patterns. Glycine (2 or 5 mM) and strychnine (5-50 microM), a glycine antagonist, were superfused over the anterior spinal hindlimb enlargement while fictive rostral scratch motor output was recorded bilaterally from hindlimb muscle nerves in the form of electroneurograms (ENGs). Although glycine reduced rostral scratch burst frequencies, strychnine tended to increase burst frequency. Strychnine also changed the shape of hip flexor ENG bursts, resulting in more abrupt burst onsets, indicating an earlier recruitment of motor neurons with large ENG spikes. During bilateral stimulation, strychnine increased the variability of interlimb phase values (left vs right hip flexor bursts) but did not abolish right-left alternation. These results indicate that glycinergic neurons in or near the anterior hindlimb enlargement contribute to the overall timing of the rostral scratch rhythm and to the recruitment timing of individual hip flexor motor neurons within each scratch burst. Our data also indicate that glycinergic mechanisms contribute to, but are not critically important for, maintaining an alternating interlimb coordination during bilateral scratch motor patterns.

Animals↗

Three cases of cat scratch disease diagnosed by indirect immunofluorescence antibody assay and/or polymerase chain reaction of 16S rRNA gene of Bartonella henselae.

Three suspected cases of cat scratch disease were diagnosed by indirect immunofluorescence antibody assay and/or polymerase chain reaction. Patient 1 was a 10-year-old female who presented swelling of the right axillary [corrected] lymph nodes with pain and fever. She kept a kitten, and many scratches were observed on her both legs and dorsum manus. Antibody titers against Bartonella (B.) henselae were 1:32 for IgM 3 weeks after the onset of the symptoms and 1:64 for IgG 8 weeks after the onset. The DNA for 16S rRNA type I of B. henselae was detected from the blood sample obtained 3 weeks after the onset of symptoms by polymerase chain reaction for the first time in Japan. Patient 2 was a 22-year-old female veterinary student with a cat scratch at the bottom of her neck by a male kitten. She developed a papule at the scratch, slight fever, and neck pain. Although both Bartonella-specific IgG and IgM antibodies were negative before the scratch, the IgG antibody titer rose to 1:512 14 weeks after the onset. B. henselae was isolated from the kitten and its DNA found to be for 16S rRNA type I by PCR. Patient 3 was a 23-year-old female veterinary student with a cat scratch on her left forearm. A small reddish papule developed on the scratch, and she experienced swelling of the left axillary [corrected] lymph node and pain. Both the IgG and IgM antibodies against B. henselae were negative before the cat scratch, and the IgG titer rose significantly to 1:128 and 1:1,024 in 2 and 5 weeks, respectively, after the onset of the symptoms.

Adult↗

Coordination between head and hindlimb motions during the cat scratch response.

Coordination between motions of the head and the hindlimb paw ipsilateral to the stimulated pinna were assessed during the scratch cycle in freely moving cats. Motor patterns were determined by electromyographic (EMG) recordings made from epimysial-patch electrodes surgically implanted on the biventer cervicis (BC), complexus (CM), obliquus capitis inferior (OC), and splenius (SP) muscles and by fine-wire EMG electrodes implanted in two ankle muscles, medial gastrocnemius (MG), and tibialis anterior (TA). To assess head motions during the three phases of the scratch cycle (precontact, contact, postcontact), several responses were filmed, and in some cats an in vivo force transducer was implanted on an ankle extensor muscle (MG or plantaris, PL) to determine the tension profile during the scratch cycle. During the scratch cycle, the head's trajectory was usually characterized by a small oscillation in which the head was pushed away during paw contact (as hindlimb joints extended) and then repositioned during the noncontact phases (as hindlimb joints flexed). Neck muscle activity did not occur during all responses or during all cycles of a single multicycle scratch response, and when it occurred, neck muscle EMG was characterized as phasic (a single burst during the cycle) or tonic (low-level activity during the entire cycle). Neck muscles ipsilateral (i) to the scratching limb exhibited phasic bursts more than contralateral (c) muscles, and phasic activity was most frequently observed in the iBC, iSP, iOC, and cOC muscles. The cOC was reciprocally active with the ipsilateral muscles, and its burst coincided with the postcontact phase and the ankle flexor (TA) burst. The ipsilateral muscles (iOC, iSP, iBC) were active during paw contact, and the termination of all three bursts occurred synchronously just after peak tension of the ankle extensor was reached. The iBC was active before the onset of paw contact and may have been responsible for repositioning the head, along with the cOC, during the precontact phase. The iOC became active after the onset of paw contact (22 ms) and was recruited more often when the peak extensor tendon force was high (10-16 N). The iSP, in contrast, was active during the contact phase of most scratch cycles examined and its recruitment appeared to be unrelated to tendon forces. Our data suggest that phasic neck muscle activity is not obligatory during the cat scratch response, but is related to certain conditions such as a higher than average tendon force of an ankle extensor during contact and the need to reposition the head during the noncontact phases of the cycle.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Messages conveyed by descending tracts during scratching in the cat. I. Activity of vestibulospinal neurons.

(1) The activity of vestibulospinal (VS) neurons giving axons to the lumbosacral spinal cord was recorded during scratching in thalamic and decerebrate cats. The most part of the experiments was carried out on curarized cats, in which fictitious scratching13, i.e. rhythmical activity of motoneurons typical of actual scratching, was evoked. (2) During both actual and fictitious scratching, the discharge frequency of many VS neurons was rhythmically modulated in relation to the scratch cycle. Most modulated neurons were maximally active in the extensor phase of the cycle. (3) The firing pattern of VS neurons during fictitious scratching was similar to that during actual scratching. Therefore, rhythmical modulation of VS neurons is determined mainly by central mechanisms and not be a rhythmical sensory input. (4) In decerebellate cats, rhythmical modulation was not found during either actual or fictitious scratching. (5) Transection of the ventral spinocerebellar tract (VSCT) resulted in considerable reduction of rhythmical modulation of VS neurons during fictitious scratching, while transection of the spino-reticulocerebellar pathway (SRCP) resulted in just a small decrease of modulation. Therefore, of the two pathways (VSCT and SRCP) transmitting messages about intraspinal processes to the cerebellum during scratching6,7, the VSCT is of major importance for modulating VS neurons.

Animals↗

Evaluation of anti-scratch properties of oxatomide and epinastine in mice.

Anti-scratch effects of oxatomide and epinastine were examined in mice. Scratching behavior and cutaneous reactions were induced in BALB/c, ICR and ddY mice by dinitrofluorobenzene painting, passive cutaneous anaphylaxis and substance P injection, respectively. Although oxatomide and epinastine failed to inhibit scratching behavior in BALB/c mice, they inhibited the cutaneous reaction significantly. The drugs potently inhibited both scratching behavior and cutaneous reaction in ICR mice. They also inhibited scratching behavior and cutaneous reaction in ddY mice, although cetirizine and terfenadine failed to affect them. Histamine did not induce frequent scratching behavior in BALB/c and ddY mice. These results indicate that oxatomide and epinastine inhibit the scratching behavior in ICR mice associated with passive cutaneous anaphylaxis mainly through an antagonistic action on histamine H(1) receptors. The results also indicate that these drugs inhibit substance P-induced scratching behavior in ddY mice through an action independent of the antagonistic action on histamine H(1) receptors.

Animals↗

The development of an objective method for measuring scratch in children with atopic dermatitis suitable for clinical use.

Itch is a major symptom of skin disease and remains poorly studied. We have used limb-worn digital accelerometers, and infrared video of patients as a gold standard, on children with atopic dermatitis and control subjects in their own homes at night. Video analysis shows that nocturnal scratching and restlessness are more complex than we first thought, with many movements that potentially damage the skin not conforming to stereotypical scratch movements. Children with atopic dermatitis spent a mean of 46 minutes less time motionless or sleeping at night than control subjects (468 +/- 3 [SEM] vs 422 +/- 37 [SEM], P<.001). Children with atopic dermatitis showed 2 to 3 times as much scratching or restlessness activity as control subjects, with little overlap between groups (P<.01). Scratching and restlessness were highly correlated with each other (0.94, P<.01). Accelerometer scores were highly correlated with video results (rho>0.02, P<.01, for scratching, restlessness, and sleeping time). Individual limb scores were highly correlated with each other (rho approximately 0.87-0.98), suggesting that little information would be lost if only 1 limb was measured. There was little relation between parental assessment of scratch and objective measured scratch. Accelerometers provide a useful and practical way of assessing scratching at night in the patient's own home and could be used as an objective measure of disease activity both in clinical trials and in everyday clinical practice.

Behavior↗

Involvement of histamine H4 and H1 receptors in scratching induced by histamine receptor agonists in Balb C mice.

The role of histamine H(1), H(2), H(3) and H(4) receptors in acute itch induced by histamine was investigated in female BalbC mice. Scratching was induced by intradermal injections of pruritogen into the back of the neck and "itch" assessed by quantifying the scratching evoked. Histamine (0.03-80 micromol), histamine-trifluoromethyl-toluidine (HTMT, H(1) agonist, 0.002-2 micromol), clobenpropit (H(4) agonist, H(3) antagonist, 0.002-0.6 micromol) and to a lesser extent imetit (H(3)/H(4) agonist, 0.03-3 micromol) all induced dose-dependent scratching. Dimaprit (H(2) agonist, 0.04-40 micromol) did not cause scratching. Mepyramine (H(1) antagonist, 20 mg kg(-1), i.p.) reduced scratching evoked by histamine and HTMT, but not that caused by H(3) or H(4) agonists. Thioperamide (H(3)/H(4) antagonist, 20 mg kg(-1), i.p.) reduced scratching induced by histamine, H(3) and H(4) agonists, but not that caused by HTMT. The non-sedating H(1) antagonist, terfenadine, also significantly reduced the scratching induced by the H(1) agonist, HTMT. Cimetidine (H(2) antagonist, 20 mg kg(-1), i.p.) did not affect histamine-induced scratching. These results indicate that activation of histamine H(4) receptors causes itch in mice, in addition to the previously recognised role for H(1) receptors in evoking itch. Histamine H(4) receptor antagonists therefore merit investigation as antipruritic agents.

Animals↗

A new analytical system for quantification scratching behaviour in mice.

BACKGROUND: Scratching behaviour is an important component of human atopic dermatitis. The duration of scratching determines the extent of skin damage and thus the rash, but quantification of this is difficult. Establishment of a method for measuring the duration of scratching is important in order to make objective assessments of the factors that may cause the itch and also the efficacy of new antipruritic drugs. OBJECTIVES: A novel method for assessing the duration of scratching in mice was evaluated, based on the time course changes in the distance between the animal's hind limbs and the back of the neck during scratching behaviour. METHODS: Compound 48/80 was administered intradermally to the back of ICR mice and their scratching behaviour was recorded on digital videotape. The distance between the back and the hind limb was measured continuously using an image analysis system. RESULTS: Measurement of the frequency and duration when the mouse's hind limb came into contact with the back of the neck provided an accurate method of quantitating scratching behaviour. CONCLUSIONS: This system provides a new method of quantifying scratching behaviour in a mouse.

Animals↗

Involvement of IL-31 on scratching behavior in NC/Nga mice with atopic-like dermatitis.

Pruritus is an important symptom in atopic dermatitis (AD), but the major pruritogen has not been identified. NC/Nga mice, spontaneously develop an eczematous AD-like skin lesion when kept under conventional conditions, but not under specific pathogen-free (SPF) conditions, have been thought to be an animal model for AD. In this study, to determine whether newly identified cytokine, IL-31, may be involved in pruritus of AD, we examined the IL-31 expression in spontaneous dermatitis model which showed itch-associated long-lasting (over 1.5 s duration) scratching behavior and compared with that of hapten-induced contact dermatitis model without itch-associated long-lasting scratching behavior, using NC/Nga mice. In NC/Nga mice cohabited with NC/Nga mice which developed severe dermatitis for 2 weeks (conventional NC/Nga mice), the numbers of long-lasting scratching counts were significantly increased. Yet in 2,4,6-trinitrochlorobenzene (TNCB)-sensitized and challenged mice (TNCB-applied NC/Nga mice), no significant increase in long-lasting scratching counts was observed. In conventional NC/Nga mice with long-lasting scratching behavior, expression of IL-31 mRNA was increased, while in TNCB-applied NC/Nga mice without long-lasting scratching behavior, the expression of IL-31 mRNA were unchanged. There was a good correlation between the scratching counts and expression of IL-31 mRNA in conventional NC/Nga mice, but not so in TNCB-applied NC/Nga mice. These results suggest that IL-31 causes the itch-associated scratching behavior in conventional NC/Nga mice, an experimental animal model for AD.

Animals↗

Effects of indomethacin and dexamethasone on mechanical scratching-induced cutaneous barrier disruption in mice.

Effects of indomethacin and dexamethasone on recovery of cutaneous barrier disruption induced by mechanical scratching were examined. Cutaneous barrier was disrupted by scratching using a stainless-steel wire brush (mechanical scratching) and compared to cutaneous application of acetone/ether (1:1) mixture (AE) and tape-stripping. Increase of transepidermal water loss (TEWL), as an indicator of a broken skin barrier, and recovery period for mechanical scratching were higher and longer than those for AE treatment and tape-stripping and we also confirmed the severity of skin damage in a histological study. Topical application of moisturizers showed a temporal effect, rapidly decreased TEWL on mechanical scratching- or AE treatment-induced cutaneous barrier disruption, and gradually increased base levels from 4 to 12 h after treatment. Topical application of indomethacin or dexamethasone prolonged the recovery period for the cutaneous barrier, and concomitant use further worsened the status of the barrier. Additionally, we examined the effects of prostaglandins (PGs) and inflammatory cytokine on mechanical scratching-induced cutaneous barrier disruption pretreated with indomethacin and dexamethasone. As a results, PGD2 and interleukin (IL)-1beta significantly accelerated the recovery of cutaneous barrier disruption by mechanical scratching but such was not the case with PGE2, IL-1alpha, and tumor necrosis factor-alpha treatment. These results suggest that indomethacin and dexamethasone prolonged the recovery period caused by inhibition of PGD2 and IL-1beta. Mechanical scratching-induced cutaneous barrier disruption may be a useful method for evaluating means of recovery from skin damage.

Acetone↗