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PubMed1991

Successful treatment of cat-scratch disease with ciprofloxacin.

Cat-scratch disease is usually a benign, self-limited disease. Infection may be asymptomatic but is commonly associated with painful regional lymphadenitis. Occasionally, disease may result in systemic symptoms and dissemination. Five adult patients, aged 24 to 57 years, were diagnosed as having cat-scratch disease, based on a positive history of cat scratches followed by typical symptoms including painful regional lymphadenitis, malaise, and positive cat-scratch skin tests. Diagnostic evaluations revealed no other cause for the lymphadenitis. Three patients had not received prior treatment with antibiotics, and two patients had failed to improve on other antibiotics. All five were treated with oral ciprofloxacin, 500 mg by mouth, twice daily. All patients had dramatic improvement in symptoms within a few days and none has relapsed during follow-up. This is the first report of successful treatment of cat-scratch disease with ciprofloxacin, which appears to be an effective therapy for cat-scratch disease in adults.

Adult↗

PubMedDate not supplied

Use of Bartonella antigens for serologic diagnosis of cat-scratch disease at a national referral center.

BACKGROUND: Bartonella henselae (formerly the genus Rochalimaea) has recently been isolated from patients with cat-scratch disease and their cats, and since September 1992 the Centers for Disease Control and Prevention has offered an indirect fluorescent antibody assay for Bartonella-specific antibody. METHODS: Physicians submitted serum samples from patients suspected of having cat-scratch disease or other Bartonella-associated illness and completed a questionnaire that recorded clinical information. Indirect fluorescent antibody assay was performed with the use of antigen derived from three Bartonella species: B henselae, Bartonella quintana, and Bartonella elizabethae. RESULTS: During 16 months, 3088 serum samples were received. The largest numbers of specimens and the highest percentages positive (titer, > or = 64) were observed in the fall and winter. Clinical histories of the first 600 patients for whom serum samples and completed information forms were received were examined in detail; seropositivity was significantly associated with cat contact, cat age of less than 1 year, cat scratch, presence of an inoculation papule, and regional adenopathy. Of 91 patients whose illness met a strict clinical definition of cat-scratch disease, 86 (95%) had titers of 64 or greater to either B henselae or B quintana. A fourfold rise or fall in titer was observed in 87 of 132 patients with paired serum samples. CONCLUSIONS: The indirect fluorescent antibody assay for Bartonella-specific antibody is sensitive for the diagnosis of cat-scratch disease. Redefinition of cat-scratch disease on the basis of cause and use of this assay as a diagnostic criterion is recommended.

Adolescent↗

PubMed1997

Electrochemical response of CoCrMo to high-speed fracture of its metal oxide using an electrochemical scratch test method.

A new test method was used to rapidly produce a controlled, repeatable scratch on the surface of CoCrMo (ASTM F75) samples, resulting in fracture of the surface oxide. Current transients resulting from ionic dissolution and repassivation of the exposed reactive alloy were measured with the samples potentiostatically held in phosphate-buffered saline. The effects of potential, contact load, pH, aeration, and proteins on the magnitude of the current transients and time constants for repassivation were determined. Using the scratch test apparatus, topographic images of scratched surfaces were constructed and used to measure scratch depth. Aeration had no significant effect on peak currents and time constants owing to the availability of oxygen from the hydrolysis of water. Peak current behavior reflected the transition regions observed in polarization curves. A decrease in peak currents in the presence of albumin may have been due to barrier effects of the adsorbed protein preventing water from reaching the sample surface, or lubrication resulting in less material removed from the surface during scratching. Peak currents and scratch depth increased with load. A model used to predict repassivation behavior was in agreement with experimental results.

Electrochemistry↗

PubMed1990

Cutaneous dermatomes for initiation of three forms of the scratch reflex in the spinal turtle.

The turtle spinal cord produces three forms of the hindlimb scratch reflex. Each scratch form is initiated in response to gentle mechanical stimulation of a distinct set of sites in the periphery, termed the receptive field for that scratch form. The turtle spinal cord consists of 8 cervical segments (C1-C8), 10 dorsal segments (D1-D10), 2 sacral segments (S1, S2), and about 16 caudal segments (Ca1-Ca16). First, we recorded cutaneous afferents in peripheral nerves to reveal the tactile dermatomes of segments D3-D8. These segments innervate regions of the body between the forelimb and hindlimb, directly lateral to their spinal cord segments. Adjacent segments innervate adjacent and partially overlapping regions of the periphery. Second, we used successive spinal cord transections combined with either a) behavioral analysis in turtles with limb movements or b) electroneurographic recordings in immobilized turtles, and mapped the zone of remaining sensibility after each transection to measure the borders of dermatomes D2-Ca2. This technique revealed that adjacent dermatomes are innervated by non-adjacent spinal segments in regions near the hip. Segments D8 and Ca1 innervate adjacent and partially overlapping regions ventral to the hip. There is a similar discontinuity in the innervation of the shell and skin dorsal to the hip. These discontinuities correlate with the innervation of the hindlimb skin by segments D8-Ca1. The rostral scratch receptive field is innervated by sensory afferents entering spinal segments D3-D6; the pocket scratch receptive field is innervated by D6-D8; the caudal scratch receptive field is innervated by S2, Ca1, and more caudal segments. The rostral-pocket transition zone is innervated mainly by one segment, D6; the ventral part of the caudal-pocket transition zone is innervated by two non-adjacent segments, D8 and Ca1. Thus the motor pattern blends elicited by stimulation of sites within the rostral-pocket transition zone must be produced in response to a very different distribution of sensory inputs than the blends elicited by stimulation of sites within the caudal-pocket transition zone.

Action Potentials↗

PubMed1998

Improved device for measuring scratching activity in patients with pruritus.

Pruritus is an inherently subjective perception that cannot be quantified. However, in trials of new therapies for pruritus, it is necessary to base assessments of therapeutic efficacy on objective quantitative criteria. This can be achieved by measuring the behavioural consequence of pruritus, scratching activity, and using an index of scratching activity as an efficacy endpoint. A portable device to monitor scratching activity in patients with pruritus is described. The key feature of this device is a piezo-element attached to a fingernail. Vibrations of the fingernail in the act of scratching induce electrical impulses in the piezo-element. Electrical signals from the device are filtered and measured. The measurements, which are not absolute, have nevertheless been shown to provide an objective index of scratching activity that is independent of arm and hand movements. An advantage of the device is that recordings can be made while the patient is in a normal, non-hospital environment, thereby obviating effects of change of environment (e.g. hospitalisation) on the intensity of pruritus. Application of the device enables data on scratching activity during periods of treatment with a test drug and with a placebo to be compared in individual patients.

Electronic Data Processing↗

PubMed2002

Both shared and specialized spinal circuitry for scratching and swimming in turtles.

In principle, nervous systems could generate a behavior either via neurons that are relatively specialized for producing one behavior or via multifunctional neurons that are shared among multiple, diverse behaviors. I recorded extracellularly from individual turtle spinal cord neurons while evoking hindlimb scratching, swimming, and withdrawal motor patterns. The majority of spinal neurons recorded were activated during both scratching and swimming motor patterns, consistent with the existence of shared circuitry for these types of limb movements. These neurons tended to have a similar degree of rhythmic modulation of their firing rate and a similar phase preference within the hip flexor activity cycle during scratching and swimming motor patterns. In addition, a substantial minority of neurons were activated during scratching motor patterns but silenced during swimming motor patterns. This raises the possibility that inhibitory interactions between some scratching and swimming neural circuitry play a role in motor pattern selection. These scratch-specialized neurons were also less likely than the putative shared neurons to be activated during withdrawal motor patterns. Thus, these neurons may represent two separate classes, one of which is used generally for hindlimb motor control and the other of which is relatively specialized for a subset of hindlimb movement types.

Action Potentials↗

PubMed1992

Effects of central administration of opioids on facial scratching in monkeys.

Epidural and intrathecal administration of opioids to humans can produce facial pruritus and scratching that is naloxone reversible. It has been proposed that opioids may act at the level of the medulla to produce facial pruritus and associated scratching behavior. We investigated the effects of mu, delta and kappa opioid-receptor agonists microinjected unilaterally into the medullary dorsal horn (MDH) on facial scratching in cynomolgus monkeys. The selective mu opioid-receptor agonist, DAMGO (3.1-25.0 ng) produced large dose-dependent, naloxone-reversible increases in facial scratches. The selective delta opioid-receptor agonist, DPDPE (1.0-5.0 micrograms) and the selective kappa opioid-receptor agonist, U-50,488H (0.1-5.0 micrograms) did not produce significant increases in facial scratching behavior. We conclude that the MDH is a site where DAMGO, a mu opioid-receptor agonist, can act to produce facial scratching in monkeys, and that the MDH is likely the site where centrally administered opioids act to produce facial pruritus in humans.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1993

Scratching behavior induced by bombesin-related peptides. Comparison of bombesin, gastrin-releasing peptide and phyllolitorins.

Bombesin and 10 bombesin-related peptides were administered intracerebroventricularly to conscious and freely moving rats. All peptides tested were found to elicit excessive grooming, especially scratching behavior. Bombesin itself had the most potent and long-lasting activity in eliciting scratching behavior. Naturally occurring peptides such as neuromedin B and gastrin-releasing peptide (GRP)-(18-27) were short-acting compared with exogenous peptides such as bombesin and synthesized analogs. Two phyllolitorins, a new bombesin subfamily, were also examined in this study. [Leu8]phyllolitorin induced more scratching than [Phe8]phyllolitorin and proved to be virtually equipotent to bombesin. Corticotropin-releasing factor (CRF) and substance P induced considerable excessive grooming, but both peptides were strikingly weak in inducing scratching behavior. It is suggested that (1) scratching represents a specific behavior commonly induced by bombesin-related peptides and (2) the relative potency to induce scratching behavior reflects the metabolic stability of the peptide, e.g. endogenous versus exogenous, shorter versus longer sequences, or chemical protection of N-terminus.

Amino Acid Sequence↗

PubMed1991

Measuring anxiety in nonhuman primates: effect of lorazepam on macaque scratching.

Lorazepam (0.2 mg/kg IM) was given to group-living female macaques to assess the effect of anxiolytic treatment on scratching, a behavior pattern referred to as a displacement activity in the primate literature. Lorazepam selectively diminished scratching behavior. The drug effect was status-dependent: especially low-ranking animals showed a marked reduction in scratching. Lorazepam exerted a direct effect on scratching, that is the effect was not due to sedation or mediated by the influence of the drug on other behaviors. These results provide pharmacological validation to the ethological finding that scratching may be a manifestation of anxiety in monkeys. In addition, they suggest to use scratching as a behavioral measure in studies investigating nonhuman primate models of anxiety.

Animals↗

PubMed1988

Neuromuscular patterns of stereotypic hindlimb behaviors in the first two postnatal months. III. Scratching and the paw-shake response in kittens.

Neuromuscular patterns of scratching and the paw-shake response were studied in normal kittens from birth to postnatal day 60. Onset of both behaviors coincided with the development of secure weight-bearing posture and occurred on postnatal day 21 for scratching and postnatal day 26 for paw shaking. At onset, cycle periods for scratching (5-6 Hz) and paw shaking (8-10 Hz) were similar to that for adult cats, and EMG patterns were adult-like. The scratch cycle consisted of reciprocal flexor and extensor bursts of equal duration, while the shake cycle consisted of coactive knee extensor and ankle flexor bursts alternately active with ankle extensor bursts. The lack of scratching and paw shaking during the first 3 postnatal weeks and the adult-like EMG patterns at onset are consistent with the hypothesis that pattern-generating circuits within lumbosacral segments are available early in development but inhibited by the rostral neuraxis until postural control is sufficient to accommodate the response. To eliminate rostral inputs, including descending input critical for postural control, kittens were spinalized at the T12 level, and onset of paw shaking was accelerated. In kittens spinalized at birth, paw-shake onset occurred on postnatal day 14, while in kittens spinalized on postnatal day 14, onset occurred 48 h after spinalization. In all spinal kittens, however, knee extensor activity was disrupted and not normal by postnatal day 60. Mature neuromuscular patterns for scratching and paw shaking are available at onset of the behavior during normal development. Spinalization hastens the onset of paw shaking but the normal neuromuscular synergy is disrupted as well as the temporal structure of the multi-cycle response. Disruptions following spinalization may be due to altered development of spinal pattern generators or aberrant feedback from atypical hindlimb motions due to a retardation of hindlimb growth and an alteration of muscle contractile properties in spinal kittens.

Age Factors↗

PubMed1994

Neonatal capsaicin treatment in rats results in scratching behavior with skin damage: potential model of non-painful dysesthesia.

We administered capsaicin or vehicle in 2-day-old rat pups, and for over 6 months examined the rats for damaged skin and for the behaviors of scratching, gnawing and biting their skin. By 35 days of age, all rats in the capsaicin group (n = 10) had damaged skin (i.e., lesions, hair loss and red skin) on the rostral half of their bodies. Skin damage remained prevalent over 6 months, whereas vehicle-treated rats (n = 8) had virtually no skin damage. Gnawing and biting behaviors were rarely observed, however, rats in the capsaicin group frequently scratched themselves. There was a significant positive correlation between the frequency at which rats scratched themselves and the total area of skin damage. Morphine (3.0 mg/kg, i.p.) greatly increased scratching behavior in only the capsaicin-treated rats and naloxone (0.5 mg/kg, i.p.) significantly reduced scratching in these rats. Thus, neonatal capsaicin, in its destruction of the majority of primary afferent C-fibers, is capable of inducing opioid-sensitive scratching behavior.

Animals↗

PubMed2004

Evaluation of antipruritic effects of several agents on scratching behavior by NC/Nga mice.

We investigated the effects of several agents on the established itching model in NC/Nga mice, model of atopic dermatitis-like disease, to elucidate related characteristics. The number of spontaneous scratching behaviors (the duration time is over 1.5 s) by NC/Nga mice with severe skin lesions was measured before and after administration of agents for 24 h. The scratching behavior by NC/Nga mice was significantly suppressed by administration of dexamethasone or tacrolimus, but not by chlorpheniramine maleate or cyproheptadine hydrochloride. These results suggest that this method shows a good correlation with the effectiveness of drugs prescribed for itching in humans with atopic dermatitis, and histamine and serotonin do not play an important role in causing the scratching behavior seen by NC/Nga mice. The scratching behavior was also significantly suppressed by naloxone hydrochloride, dibucaine or capsaicin. These results suggest that the scratching behavior seen in this model is caused by itching signal transmission through neural system. Furthermore, we found that theophylline, pinacidil or limaprost had scratching suppression effects in this model.

Alprostadil↗

PubMed2005

Prostaglandin D2 and prostaglandin E2 accelerate the recovery of cutaneous barrier disruption induced by mechanical scratching in mice.

The role of prostaglandins in mechanical scratching-induced cutaneous barrier disruption in mice was investigated. Skin prostaglandins contents were measured after cutaneous barrier function was disrupted by scratching using a stainless-steal wire brush (mechanical scratching), then effects of prostanoids on recovery of cutaneous barrier functions were examined. This mechanical scratching increased transepidermal water loss and skin prostaglandins (prostaglandin D2, prostaglandin E2, 6-keto-prostaglandin F1alpha and prostaglandin F2alpha) contents, count-dependently. Topical application of indomethacin immediately after cutaneous barrier disruption delayed the recovery period of cutaneous barrier disruption. We examined effects of several prostanoids (prostaglandin D2, prostaglandin E2, prostaglandin F2alpha, prostaglandin I2 and U46619) on delay of the recovery process of mechanical scratching-induced cutaneous barrier disruption with treatment of indomethacin. Topically applied prostaglandin D2 and prostaglandin E2 accelerated the recovery of cutaneous barrier disruption and topical application of prostaglandin J2, limaprost, sulprostone and ONO-4819, but not 13,14-dihydro-15-keto-prostaglandin D2, 15-deoxy-Delta(12,14)-prostaglandin J2, 17-phenyl-trinor-prostaglandin E2 or butaprost had effects on recovery of the cutaneous barrier. These results suggest that prostaglandin D2 and prostaglandin E2 accelerate the recovery process of cutaneous barrier disruption caused by mechanical scratching, via specific prostanoid DP1, EP3 and EP4 receptors.

6-Ketoprostaglandin F1 alpha↗

PubMed2005

Spontaneous scratching behavior in MRL/lpr mice, a possible model for pruritus in autoimmune diseases, and antipruritic activity of a novel kappa-opioid receptor agonist nalfurafine hydrochloride.

Pruritus is a common, distressing and difficult to manage complication of many autoimmune diseases. A suitable animal model of autoimmune disease associated pruritus would contribute to a better understanding of the pathophysiology of this symptom and lead to the development of safe and effective antipruritic agents. We noticed spontaneous scratching behavior in aged MRL/lpr mice, a model of autoimmune disease. This scratching behavior was observed in a specific pathogen-free environment and was more frequent in female mice. In contrast to animal models of dermatitis; NC/Nga mice, the serum IgE and IgG1 levels in MRL/lpr mice were not elevated. These features indicate that this scratching behavior is similar to human autoimmune disease associated pruritus. The antipruritic effects of an antihistamine (chlorpheniramine), an opioid receptor antagonist (naltrexone), and a novel kappa-opioid receptor agonist (nalfurafine hydrochloride [TRK-820]) were evaluated. The frequency of scratching was not reduced by oral administration of chlorpheniramine, suggesting that the behavior is antihistamine-resistant. The oral administration of nalfurafine and subcutaneously administered naltrexone inhibited the scratching behavior without causing gross behavioral changes. In conclusion, MRL/lpr mice scratching behavior is a suitable model of pruritus that occurs in autoimmune diseases, and nalfurafine was shown to be efficacious against this behavior suggesting that it may be beneficial in patients with autoimmune disease associated pruritus.

Age Factors↗

PubMed2005

Involvement of skin barrier dysfunction in itch-related scratching in special diet-fed hairless mice.

HR-1 hairless mice fed with a special diet develop atopic-like dry skin, characterized by increased transepidermal water loss, and prolonged bouts of spontaneous scratching. In this study, the role of the skin barrier dysfunction in the prolongation of scratching was evaluated. Although the prolonged scratching was dose-dependently inhibited by opioid receptor antagonist naloxone, neither H(1) receptor antagonist, mepyramine, nor 5-HT(1/2) receptor antagonist, methysergide, affected it. Thus, the prolonged scratching could be itch-related response independent of histamine and serotonin. The application of petrolatum ointment on the skin temporarily alleviated the increase of transepidermal water loss for 60 min after treatment. Due to this alleviation in barrier dysfunction, the prolongation of scratching was significantly suppressed. However, when the barrier dysfunction relapsed, the scratching worsened. Taken together, a skin barrier dysfunction is associated with the itch-related response.

Animals↗

PubMed2004

Effect of Brazilian propolis on scratching behavior induced by compound 48/80 and histamine in mice.

We studied the effect of Brazilian propolis on scratching behavior induced by compound 48/80 and histamine in ICR mice. Propolis granular A.P.C dose-related inhibited scratching behavior induced by compound 48/80 and significant inhibition were observed at 1000 mg/kg. However, histamine-induced scratching behavior was not inhibited by propolis granular A.P.C even at 1000 mg/kg. Propolis ethanol extract at 10 microg/ml or more inhibited histamine release from rat mast cells induced by compound 48/80. In addition, it blocked increased vascular permeability induced by compound 48/80. The inhibitory effect of propolis on scratching behavior induced by compound 48/80 was gradually enhanced by repeated administration, and 500 mg/kg propolis granular A.P.C, which caused no effect through single administration, significantly inhibited scratching behavior after repeated administration for 4 weeks. From these findings, it is assumed that the inhibition of scratching behavior induced by propolis occurs through a mast cell-dependent mechanism.

Animals↗

PubMed2005

A repetitive movement detector used for automatic monitoring and quantification of scratching in mice.

We have designed an economical non-invasive movement detector for small animal studies and used it for monitoring and quantifying itch in mice. The system is based on a sensitive force transducer positioned below a recording platform holding a lightweight polystyrene recording box in which an animal is placed. A programmed micro-controller is used to discriminate between non-specific movement, grooming behaviour, and scratching movements made by the animal's hind limb. Following sub-dermal injection of histamine receptor agonists into the neck of a mouse, dose-related scratching occurred which was detected and quantified. There was 91% correlation between bouts of scratching as counted manually from playback of the video recording and recorded by the detector. The detector was also able rapidly to count the individual scratch movements of the hind limb that comprise a bout, with 95% accuracy in comparison with manual counting during slow motion playback of video tape, something that is impossible for an unaided observer to achieve because individual scratch movements are too fast to discriminate by eye. Separate detectors were used for the efficient non-invasive study of four animals simultaneously, and this number could easily be increased by adding more platforms. The system could also be modified to record the animal's position within the box, which would be of value in studies involving exploratory behaviour. In summary, the non-invasive multichannel repetitive movement detector will be very useful for accurate measurement of scratching during pruritus studies in small animals, with considerable savings in staff time and effort. It should therefore be a valuable tool for helping to investigate pruritus and in the evaluation of anti-pruritic drugs.

Animals↗

PubMed2006

Influence of genotype, dose and sex on pruritogen-induced scratching behavior in the mouse.

Itch features considerable interindividual variability in humans, and initial studies using animal models have demonstrated a likely role of genetic factors in mediating such variability. In an attempt to systematically study genetic mediation of itch in the mouse such that gene identification by linkage mapping might be achieved, we examined scratching behavior induced by histamine and chloroquine in mice of 11 inbred mouse strains. Multiple chloroquine drug doses were used, revealing the existence of inverted-U dose-response relationships in every strain, allowing us to determine strain-dependent peak scratching behavior over the entire dose range. Peak chloroquine-induced scratching varied by 2.5-fold in this set of strains; scratching behavior shows moderate heritability in the mouse. The present data also reveal, for the first time, significant sex differences in pruritogen-induced scratching behavior, with female mice scratching an average of 23% more than males. Finally, a comparison of the strain means obtained here with previously collected data using nociceptive assays revealed a suggestive negative genetic correlation between chloroquine-induced itch and thermal pain, such that strains sensitive to pain are resistant to itch and vice versa. This finding may have implications both for our understanding of itch pathophysiology and for the identification of itch-related genes.

Analysis of Variance↗