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c-fos expression in superficial dorsal horn of cervical spinal cord associated with spontaneous scratching in rats with dry skin.

Using a dry skin model in rats, we assessed spontaneous itch-related scratching behavior and associated c-fos expression in the superficial dorsal horn of the spinal cord. The number of spontaneous bouts of hind limb scratching directed toward the nape of the neck was significantly higher after 5 days of topical application of acetone-diethylether-water (AEW) compared to pre-treatment levels or to control animals treated with water only. In AEW-treated animals, neurons expressing Fos-like immunoreactivity (FLI) were observed in superficial laminae of the dorsal horn at C3-C5 levels. There was a significant, positive correlation between the number of neurons in lamina I expressing FLI and the number and cumulative duration of spontaneous scratching bouts. These results suggest that this model may be useful to assess mechanisms of dry skin pruritus, and that lamina I neurons are activated as a consequence of itching and/or scratching in this model.

Animals↗

Mono- and multilayer formation by diazonium reduction on carbon surfaces monitored with atomic force microscopy "scratching".

Contact mode atomic force microscopy (AFM) was used to intentionally scratch a monolayer deposited on a pyrolyzed photoresist film (PPF). The force was set to completely remove the monolayer but not to damage the underlying PPF surface. A line profile determined across the scratch with tapping mode AFM permitted determination of the monolayer thickness from the depth of the scratch. A statistical process was devised to avoid user bias in determining the monolayer thickness and was used to determine the thickness as a function of derivatization parameters. PPF surfaces modified by reduction of diazonium ions of stilbene, biphenyl, nitrobiphenyl, terphenyl, and nitroazobenzene (NAB) were scratched and their modification layer thicknesses determined. For single-scan derivatizations of 1 mM diazonium ions to -0.6 V versus Ag+/Ag, the biphenyl and stilbene monolayers exhibited thicknesses close to those expected for true monolayers. However, more extensive derivatization resulted in multilayers up to 6.3 nm thick for the case of NAB. Such multilayers imply that electrons are transmitted through the growing film during diazonium reduction, despite the fact that electron tunneling would not be expected to be operative over such long distances. The results are consistent with a conductance increase in the growing film, which yields a partially conductive layer that can support further diazonium ion reduction and additional layer growth.

Journal Article↗

The effect of topically applied salicylic compounds on serotonin-induced scratching behaviour in hairless rats.

There is a strong need for antipruritic substances for treating itch in clinical dermatology. In one recent human study, topically applied acetylsalicylic acid has been described to rapidly decrease histamine-induced itch. We have established a model for periferally elicited pruritus by injecting serotonin into the rostral back area (neck) in rats. Using this model, we aimed to investigate the antipruritic potential of four different salicylic compounds, which all possess different skin penetration characteristics. Eighteen rats were studied for 6 weeks. Prior to serotonin injections (2 mg/ml, 50 micro l), 10 micro l of test substances was applied to a circular area 18 mm in diameter. The four substances were salicylic acid, butyl salicylate, diethylamine salicylate and salicylamide, all solubilized in dimethyl isosorbide to a concentration of 5% w/w. Diethylamine salicylate and salicylamide were previously shown to be slowly absorbed through rat skin in contrast to salicylic acid and butyl salicylate. After serotonin injections, scratching was monitored by video recording for 1.5 h. Compared with the vehicle, a lower number of scratch sequences were seen when diethylamine salicylate (P < 0.001) and salicylamide (P = 0.005) had been applied. The numbers of scratch sequences were lower with diethylamine salicylate and salicylamide than with the vehicle throughout the 1.5-h study period. We conclude that topical application of diethylamine salicylate and salicylamide could suppress serotonin-induced scratching in rats. The antipruritic effect seems to be related to the slow drug release of the two substances. The results may be clinically relevant as serotonin induces itch in humans.

Administration, Topical↗

Topical application of luteolin inhibits scratching behavior associated with allergic cutaneous reaction in mice.

The present study is aimed at evaluating the effects of luteolin on the scratching behavior associated with an allergic cutaneous reaction in mice. Elicitation of passive cutaneous anaphylaxis, and intradermal injections of compound 48/80, histamine or serotonin induced scratching behavior in ICR mice. Models of irritant contact dermatitis and allergic contact dermatitis were prepared by the topical application of 2,4-dinitrochlorobenzene (DNCB) on the ears of mice. Topical application of luteolin at concentrations of 20 and 100 mug/site significantly inhibited the number of scratching incidents associated with passive cutaneous anaphylaxis, and a similar tendency was also observed in histamine-, serotonin- and compound 48/80-evoked cutaneous reactions. The vascular permeability increase induced by passive cutaneous anaphylaxis or histamine injection was also significantly reduced by luteolin. Luteolin showed a potent inhibition on the ear thickness increase in models of irritant contact dermatitis and allergic contact dermatitis. In conclusion, luteolin significantly inhibited the scratching behavior associated with allergic cutaneous anaphylaxis. Its effects against pruritus are mainly attributed to its inhibition of mediator release from activated mast cells and direct antagonist effects on the released mediators which may act as local pruritogens.

Administration, Cutaneous↗

Ground scratching and preferred leg use in domestic chicks: changes in motor control in the first two weeks post-hatching.

Lateralisation of a variety of visual functions: food discrimination, fear response, copulation, and performance of topographical and other tasks, such as olfactory and auditory functions, have been described in the domestic chick, Gallus gallus domesticus. A bias to left hemisphere control on day 8 and to the right on day 11 has also been demonstrated in the domestic chick. In this study we show that motor control as to foot preference in initiating a scratching bout and a tape-removing task is lateralised in both adults and chicks. There was a preference for the right leg to initiate a bout of ground scratching in both male and female adult birds. Second, foot preference is also affected by the changes in shifts of bias on day 8 and day 11. The right leg preference in initiating a ground scratching bout observed on day 5 is reversed to a left leg preference on day 8. This then reverts to the right leg preference after day 11. Hence it is postulated that the hemisphere that is not activated due to the bias of age controls the first leg to be used in initiating routine movements such as ground scratching. For the tape-removing task the right leg was used to remove a tape adhered to the beak of the chick for the trained group on day 8; but there was no preference in the naive group. Similarly, on day 11 a left foot bias was observed for the trained group and right foot bias for the naive group. To remove a tape the activated hemisphere on days of bias is used; whereas in a novel situation the foot use is reversed. Thus, footedness is affected by age, type of task, and changing hemispheric dominance.

Journal Article↗

Noxious heat and scratching decrease histamine-induced itch and skin blood flow.

The aim of this study was to assess the effect of thermal stimuli or distal scratching on skin blood flow and histamine-induced itch in healthy volunteers. Twenty-one healthy volunteers participated in the study. Baseline measurements of skin blood flow were obtained on the flexor aspect of the forearm. These measurements were compared with skin blood flow after various stimuli: heating the skin, cooling the skin, noxious cold 2 degrees C, noxious heat 49 degrees C, and scratching via a brush with controlled pressure. Afterwards histamine iontophoresis was performed and skin blood flow and itch intensity were measured immediately after the above-mentioned stimuli. Scratching reduced mean histamine-induced skin blood flow and itch intensity. Noxious heat pain increased basal skin blood flow but reduced histamine-induced maximal skin blood flow and itch intensity. Cold pain and cooling reduced itch intensity, but neither affected histamine-induced skin blood flow. Sub-noxious warming the skin did not affect the skin blood flow or itch intensity. These findings suggest that heat pain and scratching may inhibit itch through a neurogenic mechanism that also affects skin blood flow.

Cold Temperature↗

Topical glucocorticoid augments scratching behaviour in dinitrofluorobenzene-sensitized mice by the induction of substance P.

Topical glucocorticoid (GC) is commonly applied in atopic dermatitis treatment. However, the chronic use of GC may be associated with significant side effects. In this study, we investigated whether long-term epicutaneous application of GC modulates scratching behaviour in dinitrofluorobenzene (DNFB) contact-sensitized mice. After challenge with DNFB, scratching behaviour was increased in DNFB-sensitized mice treated with GC in contrast to control mice. In addition, reverse transcriptase-polymerase chain reaction analysis demonstrated that the expression of preprotachykinin-A (PPT-A) mRNA, a precursor of substance P (SP), and inducible nitric oxide synthase (iNOS) mRNA in mice, to which GC was applied, was only observed. In order to evaluate the factors responsible for the augmented scratching behaviour, we injected various cytokines (interleukin-1alpha (IL-1alpha), IL-2, IL-3 and tumour necrosis factor-alpha (TNF-alpha)) subcutaneously into the ear of DNFB contact-sensitized mice before DNFB challenge. Among the cytokines, only IL-3 and TNF-alpha significantly increased scratching behaviour in DNFB contact dermatitis mice. Furthermore, PPT-A mRNA was only expressed in mice pre-injected with IL-3 before challenge, but not in those pre-injected with other cytokines. Taken together, our results suggest that topical GC may augment the itching sensation in DNFB-sensitized mice through modulation of iNOS and SP induced by IL-3.

Administration, Topical↗

Dermal mast cells play a central role in the incidence of scratching behavior in mice induced by multiple application of the hapten, 2,4,6-trinitrochlorobenzene.

Repeated application of 1% 2,4,6-trinitrochlorobenzene (TNCB) in acetone solution causes chronic skin inflammation in BALB/c mice. Associated scratching behavior gradually appeared, and chronic scratching behavior was established over 40 days after the initial application of TNCB. In order to explore the possible involvement of T cells and mast cells in the appearance of pruritus, we examined the response of athymic nude mice and genetically mast-cell-deficient mice. We could not detect either severe skin inflammation or immunoglobulin (Ig)E production in T-cell-deficient BALB/c nu/nu mice even after 80 days of TNCB treatment, whereas typical severe skin inflammation and IgE production were observed in mast-cell-deficient WBB6F1-W/Wv and WBB6F1-Sl/Sld mice. Furthermore, we observed persistent scratching behavior in WBB6F1-W/Wv mice, but not in BALB/c nu/nu and WBB6F1-Sl/Sld mice. Histological examination of TNCB-treated animals revealed the development of dermal mast cells in W/Wv mice but not in Sl/Sld mice. Degranulation of dermal mast cells was observed in the WBB6F1-W/Wv genotype, but most mast cells remained intact in TNCB-treated BALB/c nu/nu mice. These results suggest that mast cells play a pivotal role in the incidence of scratching behavior in this chronic pruritus model.

Acetone↗

Synaptic control of hindlimb motoneurones during three forms of the fictive scratch reflex in the turtle.

1. The turtle spinal cord produces three forms of the fictive scratch reflex in response to tactile stimulation of sites on the body surface. Common to all three forms is the rhythmic alternation of activity between hip protractor and hip retractor motoneurones. Hip protractor motoneurone activity is monitored via nerves innervating the hip protractor muscle puboischiofemoralis internus pars anteroventralis (VP-HP). Hip retractor activity is monitored via nerves innervating several monoarticular hip retractor muscles, one hip adductor muscle, and several biarticular hip retractor-knee flexor muscles (HR-KF). Each form is characterized by the timing of activity of motoneurones innervating femorotibialis (FT-KE), a monoarticular knee extensor muscle, within this alternating cycle (Robertson, Mortin, Keifer & Stein, 1985). In the present study, intracellular recordings revealed a corresponding regulation of synaptic drive to knee extensor motoneurones with respect to the synaptic drive to the motoneurones innervating antagonist muscles of the hip. These patterns of synaptic activation give rise to the distinct motor pattern underlying each form of the scratch reflex. 2. VP-HP, HR-KF and FT-KE motoneurones all exhibited phasic depolarizing and hyperpolarizing changes in membrane voltage during the production of the rhythmic motor patterns underlying each stratch form. Membrane depolarization is caused by synaptic excitation (EPSPs) and gives rise to motoneurone discharge. Hyperpolarization is primarily the result of postsynaptic inhibition (IPSPs) mediated by an increased conductance of chloride ions (Cl-) and ensures motor pool quiescence during antagonist activation. 3. VP-HP motoneurones depolarized during activation of the VP-HP motor pool and hyperpolarized during activation of the HR-KF motor pool. HR-KF motoneurones depolarized during activation of the HR-KF motor pool and hyperpolarized during activation of the VP-HP motor pool. In many cases, the amplitude of hyperpolarization was directly related to the intensity of the antagonist motor pool burst. During the rostral scratch, HR-KF motor pool activity was sometimes deleted, along with the depolarizing wave in HR-KF motoneurones and the hyperpolarizing wave in VP-HP motoneurones. The interneurones providing the synaptic drive to these antagonist motoneurones appear, therefore, to have reciprocal activation patterns. 4. FT-KE motoneurones depolarized during FT-KE motor pool activation and hyperpolarized during FT-KE motor pool quiescence. This alternation of opposing synaptic drive underlies the rhythmic activation of the FT-KE motor pool during all scratch forms.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

The utility of testing tactile perception of direction of scratch as a sensitive clinical sign of posterior column dysfunction in spinal cord disorders.

Classical beliefs about the functions of the dorsal columns of the spinal cord have been attacked following recent evidence that position and vibration sensations may be carried in the dorsal spinocerebellar tracts. There is evidence that the one specific function of the dorsal columns is for the transmission of information concerning the direction of tactile cutaneous movement. Thirty normal controls, 43 patients with spinal cord disorders and 10 patients with functional disorders were examined prospectively using an easily administered "direction of scratch" protocol. Interpretation of the direction of a 2 cm vertical tactile cutaneous movement over the lower limbs was found to be accurate in normal controls and grossly inaccurate in patients with functional disorders, exceeding the error rate of guessing. Detection of direction of 2 cm scratch was moderately impaired in 11 of 13 patients with spastic paraparesis and preserved sensation to all other modalities and 23 of 24 patients with spastic paraparesis and impaired proprioception and/or vibration sensations. Direction of 2 cm scratch, proprioception and vibration sensations were preserved in the three cases with anterior spinal cord syndromes. It is proposed that tactile perception of direction of 2 cm scratch over the lower limbs is a sensitive sign of posterior column function which can be usefully incorporated into the clinical sensory examination in the evaluation of spinal cord disorders.

Adolescent↗

Itch and motivation to scratch: an investigation of the central and peripheral correlates of allergen- and histamine-induced itch in humans.

Intense itch and urge to scratch are the major symptoms of many chronic skin ailments, which are increasingly common. Vicious itch-scratch cycles are readily established and may diminish quality of life for those afflicted. We investigated peripheral and central processing of two types of itch sensation elicited by skin-prick tests of histamine and allergen solutions. Itch-related skin blood flow changes were measured by laser Doppler in 14 subjects responsive to type I allergens and 14 nonatopic subjects. In addition, this study examined central processing of both types of itch using functional magnetic resonance imaging (fMRI). Itch perception and blood flow changes were significantly greater when itch was induced by allergens compared with histamine. Both types of itch correlated significantly with activity in the genual anterior cingulate, striatum, and thalamus. Moreover, itch elicited by allergens activated orbitofrontal, supplementary motor, and posterior parietal areas. Histamine-induced itch also significantly correlated with activation in the insula bilaterally. The identification of limbic and ventral prefrontal activation in two types of itch processing likely reflects the subjects' desire to relieve the itch sensation by scratching, and these regions have been repeatedly associated with motivation processing. A dysfunction of the striato-thalamo-orbitofrontal circuit is believed to underlie the failure to regulate motivational drive in disorders associated with strong urges, e.g., addiction and obsessive compulsive disorder. The patterns of itch-induced activation reported here may help explain why chronic itch sufferers frequently self-harm through uncontrollable itch-scratch cycles.

Adult↗

Deletions of rhythmic motoneuron activity during fictive locomotion and scratch provide clues to the organization of the mammalian central pattern generator.

We examined the features of spontaneous deletions of bursts of motoneuron activity that can occur within otherwise rhythmic alternating flexor and extensor activity during fictive locomotion and scratch in adult decerebrate cats. Deletions of activity were observed both in hindlimb flexor and extensor motoneuron pools during brain stem-stimulation-evoked fictive locomotion but only in extensors during fictive scratch. Paired intracellular motoneuron recordings showed that deletions reduced the depolarization of homonymous motoneurons in qualitatively similar ways. Differences occurred in the extent to which activity in synergist motoneuron pools operating at other joints within the limb was reduced during deletions. The timing of the rhythmic activity that followed a deletion was often at an integer multiple of the preexisting locomotor or scratch cycle period. This maintenance of cycle period was also seen during deletions in which there was a complete failure of motoneuron depolarization. The activity of antagonist motoneurons was usually sustained during deletions with some rhythmic modulation at intervals of the preexisting cycle period. We discuss an organization of the central pattern generator for locomotion and scratch that functions as a single rhythm generator with separate and multiple pattern formation modules for controlling the hyper- and depolarization of subsets of motoneurons within the limb.

Animals↗

Contralateral coordination and retargeting of limb movements during scratching in the locust

Locusts, Schistocerca gregaria, in common with many limbed vertebrates, can make directed scratching movements in response to tactile stimulation. For instance, stimulation of different sites on a wing elicits different movements that are accurately targeted so that the hindleg tarsus passes across the stimulus site. I have analysed these limb movements to define the ability of a locust to target stimulus sites correctly under a range of experimental conditions. In particular, I describe aspects of the behaviour that reveal possible neuronal pathways underlying the responses. These neuronal pathways will be the subject of further physiological analyses. Limb targeting during scratching is continuously graded in form; different patterns of movement are not separated by sharp transitions. The computation of limb trajectory takes into account the starting posture of the hindleg, so that different trajectories can be used to reach a common stimulus site from different starting postures. Moreover, the trajectories of the two hindlegs moving simultaneously from different starting postures in response to a single stimulus can be different, so that their tarsi converge onto the common stimulus site. Different trajectories can be used to reach a common stimulus site from the same start posture. Targeting information from a forewing is passed not only down the nerve cord to the ipsilateral hindleg but also across the nerve cord, so that the contralateral hindleg can also make directed movements. This contralateral transmission does not rely on peripheral sensory feedback. When the stimulus site moves during a rhythmical scratch, the targeting of subsequent cycles reflects this change. Both ipsilateral and contralateral hindlegs can retarget their movements. The trajectory of a single cycle of scratching directed towards a particular stimulus site can be modified after it has begun, so that the tarsus is redirected towards a new stimulus site.

Journal Article↗

The influence of scratches to metallic counterfaces on the wear of ultra-high molecular weight polyethylene.

A number of studies of explanted metallic femoral heads have shown scratches or damage caused by bone cement, bone or metallic particles. This damage has been cited as a cause of increased wear of ultra-high molecular weight polyethylene (UHMWPE) acetabular cups. In this laboratory study, small scratches 2 mu m deep were made on smooth stainless steel surfaces at a spacing of 10 mm. These individual scratches were found to increase the wear rate of UHMWPE by a factor of 30 in unidirectional sliding and a factor of 70 in reciprocating motion. It is of particular concern that a single small scratch, which is not detected by the average surface roughness measurement Ra can cause such a dramatic increase in the wear of ultra-high molecular weight polyethylene.

Biocompatible Materials↗

Effect of Lo Han Kuo (Siraitia grosvenori Swingle) on nasal rubbing and scratching behavior in ICR mice.

We studied the effect of Lo Han Kuo (Siraitia grosvenori Swingle) on histamine-induced nasal rubbing and compound 48/80-induced skin scratching behavior in ICR mice. An extract and glycoside (a complex of sweet components) of Lo Han Kuo were used in the study. Both the extract and glycoside caused no significant effect on nasal rubbing or scratching behavior, even at a dose of 1000 mg/kg when administered in a single dose. However, the effect of Lo Han Kuo became clear after repeated administration, and 300 and 1000 mg/kg of both extract and glycoside significantly inhibited nasal rubbing and skin scratching behavior after consecutive treatment for 4 weeks. Both the extract and glycoside inhibited the histamine release induced by compound 48/80 at concentrations of 300 and 1000 microg/ml. From these results, it is assumed that the inhibition of nasal rubbing and skin scratching behavior induced by Lo Han Kuo occurs through a mast cell-dependent mechanism.

Animals↗

Prostaglandin D2 inhibits IgE-mediated scratching by suppressing histamine release from mast cells.

Effects of prostaglandin (PG) D(2), PGE(2), and PGI(2) on itch-associated scratching responses of mice and histamine release from the rat basophilic leukemia cell line RBL-2H3 were examined. PGD(2) and ketotifen but not PGE(2) and PGI(2) suppressed the scratching caused by ovalbumin injected into ovalbumin-sensitized mice. Ketotifen also suppressed compound 48/80-induced scratching but not PGD(2), PGE(2), and PGI(2). In vitro, PGD(2) suppressed the antigen-induced histamine release from RBL-2H3 cells, but PGE(2) and PGI(2) did not. These findings suggest that PGD(2) specifically suppressed IgE-mediated scratching by inhibiting IgE-mediated histamine release from mast cells.

Animals↗

Periodic high-conductance states in spinal neurons during scratch-like network activity in adult turtles.

Intense synaptic activity may alter the response properties of neurons in highly interconnected networks. Here we investigate whether the excitability and the intrinsic response properties of neurons in the spinal cord are affected by the increased synaptic conductance during functional network activity. Scratch episodes were induced by mechanical stimulation in the isolated carapace-spinal cord preparation from the adult turtle. Intracellular recordings revealed a dramatic increase in synaptic activity in interneurons and motoneurons during scratch activity. Superimposed slow depolarizing waves were phase-related to the rhythmic bouts of spike activity in the hip flexor nerve. The increase in synaptic conductance in interneurons and motoneurons varied with the scratch rhythm. During individual episodes, the conductance shifted smoothly with the scratch rhythm from near-resting levels to levels two to four times higher. In slice experiments, we found that even moderate increases in the conductance of motoneurons suppressed the slow afterhyperpolarization and the plateau potentials. We conclude that the excitability and the intrinsic response properties of spinal neurons are periodically quenched by high synaptic conductance during functional network activity.

Action Potentials↗

Effects of disinfecting alginate impressions on the scratch hardness of stone models.

This study investigated the effects of disinfecting alginate impressions on the scratch depth of resultant stone models. Eleven brands of alginate impression material and two disinfectants, 1% sodium hypochlorite and 2% glutaraldehyde, were used. Impressions were immersed in disinfectant solutions or stored in sealed bags after spraying with disinfectants, and then poured with a type V dental stone. The scratch depth of the stone model obtained from disinfected impression was measured. The storage of alginate impressions after spraying with disinfectants did not increase the scratch depth of resultant stone models. However, the effect of immersion in disinfectants on scratch depth varied with the brand of the alginate impression material.

Alginates↗