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Itch (pruritus) is a sensation in the skin that provokes the desire to scratch. The sensation of itch is mediated through a subclass of primary afferent sensory neurons, termed pruriceptors, which express molecular receptors that are activated by itch-evoking ligands. Also expressed in pruriceptors are several types of Transient Receptor Potential (TRP) channels. TRP channels are a diverse class of cation channels that are responsive to various somatosensory stimuli like touch, pain, itch, and temperature. In pruriceptors, TRP channels can be activated through intracellular signaling cascades initiated by pruritogen receptors and underly neuronal activation. In this review, we discuss the role of TRP channels TRPA1, TRPV1, TRPV2, TRPV3, TRPV4, TRPM8, and TRPC3/4 in acute and chronic pruritus. Since these channels often mediate itch in association with pruritogen receptors, we also discuss Mas-related G-protein-coupled receptors (Mrgprs) and protease-activated receptors (PARs). Additionally, we cover the exciting therapeutic targets amongst the TRP family, as well as Mrgprs and PARs for the treatment of pruritus.

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Itch is a discrete and irritating sensation tightly coupled to a drive to scratch. Acute scratching developed evolutionarily as an adaptive defense against skin irritants, pathogens, or parasites. In contrast, the itch-scratch cycle in chronic itch is harmful, inducing escalating itch and skin damage. Clinically and preclinically, scratching incidence is currently evaluated as a unidimensional motor parameter and believed to reflect itch severity. We propose that scratching, when appreciated as a complex, multidimensional motor behavior, will yield greater insight into the nature of itch and the organization of neural circuits driving repetitive motor patterns. We outline the limitations of standard measurements of scratching in rodent models and present new approaches to observe and quantify itch-evoked scratching. We argue that accurate quantitative measurements of scratching are critical for dissecting the molecular, cellular, and circuit mechanisms underlying itch and for preclinical development of therapeutic interventions for acute and chronic itch disorders.

Background and Objectives: Allergic contact dermatitis is a common type IV hypersensitivity reaction characterised by redness, itching, oedema and thickening of the skin. It occurs in about 7% of the population and its incidence is increasing. It has been observed that the preconditioning of tissues by exposing them to transient ischemia increases resistance to subsequent permanent ischemia, and this phenomenon is called ischemic preconditioning. It has been shown that conditioning in one organ can also protect other organs. The protective effect of remote ischemic preconditioning is thought to be based on the induction of anti-inflammatory responses. The aim of this project was to investigate the anti-inflammatory and antipruritic effects of remote ischemic postconditioning in a mouse model of experimental allergic contact dermatitis. Methods: Experimental allergic contact dermatitis was induced with 1-fluoro-2,4-dinitrobenzene. Remote ischemic postconditioning was performed at 3 and 25 h after the challenge. Ear thickness and number of scratches 24 and 48 h after challenge, as well as cytokine levels and the infiltration of mast cells, neutrophils, CD4+ and CD8+ T lymphocytes in serum and ear tissue at 48 h were measured to determine the effect of RIPsC. Results: Remote ischemic postconditioning decreased ear thickness, one of the symptoms of allergic contact dermatitis (p < 0.0001). It had no significant effect on the number of scratches. It reduced serum IL-17 levels (p < 0.01). It alleviated local inflammation by suppressing CD8+ T lymphocyte and neutrophil infiltration. Conclusions: It was concluded that remote ischemic postconditioning may alleviate the symptoms of allergic contact dermatitis by suppressing CD8+ T lymphocyte and neutrophil infiltration and reducing IL-17 secretion. [ABSTRACT FROM AUTHOR]

Preference responses of cats for scratching fabrics commonly used on furniture were evaluated during four consecutive days in three Non-Governmental Organizations (NGOs) that rescue companion animals. Cats were grouped and their choices were registered at a group level (no individual identification). Daily choices for chenille, suede, synthetic leather, or waterproof grosgrain fabrics were evaluated for the cats' groups. A preference for chenille and non-preference for synthetic leather and waterproof grosgrain was found, independent of the NGO. In conclusion, although not using chenille does not assure that cats stop scratching furniture – especially if no other option to scratch is available – synthetic leather and waterproof grosgrain seem to be less attractive fabrics for these animals. Further studies are needed to investigate whether these findings apply to cats in a home scenario, when just one or a few individuals are usually present and only one type of fabric covering furniture is commonly available. Although we did not investigate the effect of providing scratching posts for these animals, we recommend such posts are available in the environment as scratching behavior is important to cats. [ABSTRACT FROM AUTHOR]

Objective Self-grooming can be induced by stressful situations. External stimuli such as house dust mites (HDM) allergen can cause acute itch sensations that lead to scratching behavior. This pilot study compared grooming and scratching behavior between mice that exposed to allergen and placebo as well as the correlation between the two behaviors. Methods This experimental pilot study involved six to eight weeks old male BALB/c mice, divided randomly into 2 groups, 8 mice each. The first group underwent the treatment of patch and spray with Dermatophagoides pteronyssinus allergen extract, while the second group was given placebo. The assessment for grooming and scratching was done on day 8. Grooming behavior assessed in this study consisted of total grooming chain with cephalocaudal pattern, grooming with noncephalocaudal pattern, interrupted grooming bouts, body grooming, and total grooming duration. Results The amount of grooming activity (number of bouts and time spent grooming) and number of non-chain (non-cephalocaudal pattern) grooming as well as the scratching bouts were higher in HDM allergen group compared to placebo group. The agreement between two researchers for grooming and scratching evaluation was assessed and showed substantial to almost perfect agreement with ĸ ranged between 0.535-0.911 and p <0.001. The difference between two groups was significant for the scratching bouts (p=0.017), non-chain patterned grooming (p=0.022), body grooming (p=0.014) and grooming duration (p=0.008). The correlation between scratching bouts and total grooming duration, scratching bouts and non-chain patterned grooming, as well as scratching bouts and body grooming had high positive correlation. Conclusion House dust mite allergen increased grooming and scratching behavior in mice compared to placebo. There were positive correlations between scratching behavior and non-chain patterned grooming, body grooming and duration of grooming, which could indicate the anxiety or stressful situation caused by itchiness from HDM allergen. [ABSTRACT FROM AUTHOR]

This letter provides a concise review of the pertinent literature on visual and tactile hallucinations in elderly patients. The discussion addresses differential diagnoses and potential underlying mechanisms, as well as the psychopathology associated with tactile hallucinations, and emphasizes the necessity for investigation into the possibility of coexisting delusional infestation (parasitosis). These symptoms frequently manifest in patients with primary psychotic disorders, organic mental disorders, and substance use disorders. The proposed pathophysiological mechanisms may involve dopaminergic imbalances and dysfunction of the striatal dopamine transporter., Competing Interests: Conflict-of-interest statement: The author reports no relevant conflicts of interest for this article., (©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background and Objectives: Allergic contact dermatitis is a common type IV hypersensitivity reaction characterised by redness, itching, oedema and thickening of the skin. It occurs in about 7% of the population and its incidence is increasing. It has been observed that the preconditioning of tissues by exposing them to transient ischemia increases resistance to subsequent permanent ischemia, and this phenomenon is called ischemic preconditioning. It has been shown that conditioning in one organ can also protect other organs. The protective effect of remote ischemic preconditioning is thought to be based on the induction of anti-inflammatory responses. The aim of this project was to investigate the anti-inflammatory and antipruritic effects of remote ischemic postconditioning in a mouse model of experimental allergic contact dermatitis. Methods: Experimental allergic contact dermatitis was induced with 1-fluoro-2,4-dinitrobenzene. Remote ischemic postconditioning was performed at 3 and 25 h after the challenge. Ear thickness and number of scratches 24 and 48 h after challenge, as well as cytokine levels and the infiltration of mast cells, neutrophils, CD4+ and CD8+ T lymphocytes in serum and ear tissue at 48 h were measured to determine the effect of RIPsC. Results: Remote ischemic postconditioning decreased ear thickness, one of the symptoms of allergic contact dermatitis (p < 0.0001). It had no significant effect on the number of scratches. It reduced serum IL-17 levels (p < 0.01). It alleviated local inflammation by suppressing CD8+ T lymphocyte and neutrophil infiltration. Conclusions: It was concluded that remote ischemic postconditioning may alleviate the symptoms of allergic contact dermatitis by suppressing CD8+ T lymphocyte and neutrophil infiltration and reducing IL-17 secretion.

Previously the effect of the pruritogens, such as histamine and chloroquine, was tested in 11 inbred mouse strains, and this study aimed to identify resistant and sensitive strains, consistent with the observation that underlies the large variability in human populations. In the present study, we used the low responder C3H/HeJ (C3H) and the more sensitive C57BL/6J (C57) strain to find out if resistance and sensitivity to develop pruritus is restricted to only histamine and chloroquine or extends to other known pruritogens as well. We tested five additional commonly known pruritogens. We established dose- response relationships by injecting four concentrations of the pruritogens in the range of 0.3, 1, 3, and ten-fold in the nuchal fold. Then we assessed the scratching behavior for 30min after injection with an automated custom- designed device based on the bilateral implantation of mini-magnets in the hind paws and on single cages placed within a magnetic coil. We found that the resistance to pruritogens is a general phenotype of the C3H strain and extends to all pruritogens tested, including not only histamine and chloroquine, but also endothelin, trypsin, 5-HT (serotonin), the short peptide SLIGRL, and Lysophosphatidic acid (LPA). C57 was more sensitive to all pruritogens and, in contrast to C3H, dose-response relationships were evident for some of the pruritogens. In general, comparable peak scratch responses were observed for the 0.3-fold concentrations of the pruritogens in C57 whereas C3H required at least the ten-fold concentration and still displayed only between 5 and 33% of the scratch responses observed in C57 for the respective pruritogen. The general resistance to pruritogens and the low level of scratching behavior found in the C3H strain is an interesting trait and represents a model for the study of the heritability of itch. It is accompanied in C3H with a higher sensitivity in assays of nociception. [ABSTRACT FROM AUTHOR]

Objective To compare and analyze the effectiveness of different pruritogens on the itch model in rats. Methods A total of 240 healthy male SD rats aged 3 to 4 months were selected and divided into 3 groups: histamine-dependent pruritogens group (histamine phosphate, compound 48/80), non-histamine-dependent pruritogens group (5-HT, chloroquine and endothelin-1) and normal saline control group. The neck and cheek were selected as the itching area to compare the itching effects of different doses (low, medium and high concentrations) of pruritogens within 30 min after intradermal injection. The difference in the frequency of hind limb scratching was recorded by using the hind limb magnetic ring combined with behavior recording box system. The changes of sensory nerve endings evoked potential in the skin and the mast cells in subcutaneous tissue were observed and analyzed by means of multi-channel physiological signal acquisition and processing system and toluidine blue staining. Results In the histamine-dependent pruritogens group, only compound 48/80 at medium and high concentrations induced the increment of times of neck and cheek scratching, which was significantly different from the control group (P < 0.05); increases in frequency and amplitude of sensory nerve endings evoked potential (P < 0.05); and elevated number of mast cells near the blood vessels in the subcutaneous tissue (P < 0.05). And, increased times of scratching in neck and cheek were observed in the phosphohistamine group after injection of the 3 concentrations (P < 0.05). High concentration enhanced the frequency of subcutaneous evoked potential and increased the number of mast cells between the control group and the histamine phosphate group (both P < 0.05). Conclusion The best itch effectiveness is induced by 5-HT in rats, even with low concentration. While, histamine-dependent pruritogens compound 48/80 and non-histamine-dependent pruritogens chloroquine and endothelin-1 are only effective at medium to high concentrations. Histamine fails to induce scratching behaviors, and is difficult to induce the model.

The occurrence of scratches on silicon wafers during chemical mechanical polishing (CMP) is a common phenomenon that significantly affects the structural stability and electrical characteristics of integrated circuits. The complex interplay between abrasives, inorganic and organic substances in an aqueous environment, and the iterative evolution of surface morphology, collectively contribute to the limited understanding of CMP-induced scratches. This paper explores the full-plane scratch shape, directions, and number density on different crystal orientations, the microscopic form of scratches with plastic and brittle features for Si(111), Si(110), and Si(100) by the diamond particle doping method. The CMP scratches observed by profilometry display a plastic-like morphology and show no directional preference, irrespective of crystal orientation. The Si(110) exhibits the fewest scratches, while Si(111) has the most, with the volume modulus being a significant factor in this variation. The nature of CMP scratches, the material removal process due to polishing slurries, and the smoothing effect of hillock abrasion and by-product refilling are substantiated by an atomic force microscope and a high-resolution transmission electron microscope. During CMP, the relaxation effect of water solvent and hydrated oxide layer mitigates the hard touching between abrasives and silicon wafer, reducing the brittleness of silicon and the depth of sub-surface damage. The height of scratch hillocks is reduced through continuous scratching of polishing abrasives, and the bottom of scratches is covered by amorphous silica and a small amount of polycrystal silicon. The Fourier transform of transmission electron microscopic images shows the quasi-plastic nature of CMP scratches, indicating the disparity of filling materials between CMP scratches and scratches generated in dry air. This work highlights the distinct nature of CMP scratches, offering insights for guiding the manufacturing of defect-free ultrasmooth silicon wafers. [ABSTRACT FROM AUTHOR]

Incorporating graphene into the CoCrFeNiMn high entropy alloy (HEA) significantly enhances the overall mechanical properties as have been verified experimentally. However, due to the limited technical analysis, the atomic-scale deformation mechanism of graphene interface has not been fully elucidated. In this work, molecular dynamics (MD) simulation is conducted to reveal the strengthening and plastic mechanism in CoCrFeNiMn HEA/graphene with a laminated structure. The weak interaction at graphene and HEA interface leads to a low shear resistance, which facilitates dislocation absorption. As a result, the competition mechanism between the "weakening effect" from the graphene/HEA interface and the "load-bearing capacity" from the graphene dominates the overall properties in graphene/high entropy alloy laminates. The size-dependent strengthening of the composite is therefore attributed to the crucial role played by the extent of graphene in bearing applied loads. These findings highlight the significance of graphene deformation for strengthening enhancement and providing guidance to design HEA composites. [Display omitted] [ABSTRACT FROM AUTHOR]

The evaluation of scratching behavior is important in experimental animals because there is significant interest in elucidating mechanisms and developing medications for itching. The scratching behavior is classically quantified by human observation, but it is labor-intensive and has low throughput. We previously established an automated scratching detection method using a convolutional recurrent neural network (CRNN). The established CRNN model was trained by white mice (BALB/c), and it could predict their scratching bouts and duration. However, its performance in black mice (C57BL/6) is insufficient. Here, we established a model for black mice to increase prediction accuracy. Scratching behavior in black mice was elicited by serotonin administration, and their behavior was recorded using a video camera. The videos were carefully observed, and each frame was manually labeled as scratching or other behavior. The CRNN model was trained using the labels and predicted the first-look videos. In addition, posterior filters were set to remove unlikely short predictions. The newly trained CRNN could sufficiently detect scratching behavior in black mice (sensitivity, 98.1%; positive predictive rate, 94.0%). Thus, our established CRNN and posterior filter successfully predicted the scratching behavior in black mice, highlighting that our workflow can be useful, regardless of the mouse strain. [ABSTRACT FROM AUTHOR]

The aim of the experiment was to investigate the effects of treadmill exercise on postthoracotomy pain and the expression of spinal pro-inflammatory and anti-inflammatory cytokines. Animals were randomly distributed into four groups: (a) sham surgery, (b) rats following 60 min thoracotomy and rib retraction (thoracotomy), (c) thoracotomy rats received treadmill training (thoracotomy+treadmill), and (d) sham surgery rats received treadmill training (sham surgery+treadmill). Treadmill workouts were started on postoperative day 10 (POD10) and lasted for 6 weeks (5 days per week). Rats were examined for cold allodynia using acetone and mechanical allodynia using von Frey hairs (in grams) at the surgical site. Spinal pro-inflammatory and anti-inflammatory cytokines were analyzed on PODs 28 and 49. Both thoracotomy and thoracotomy+treadmill groups exhibited a decrease in mechanical force thresholds (g) and an increase in scratches per min on POD10. Mechanical hypersensitivity and incremental scratches lasted from POD14 and POD49 in the thoracotomy group. Although force thresholds and scratches remained not return to baseline, incremental force thresholds (p < 0.001) and diminutive scratches (p < 0.001) occurred after 6-week treadmill workouts. The rise in spinal interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) concentrations or the decline in spinal IL-10 concentration in thoracotomy+treadmill rats was less (p < 0.05) than thoracotomy rats without exercise. Mechanical allodynia using von Frey filament testing and cold allodynia by acetone testing were improved in thoracotomy rats after treadmill workouts.. Treadmill exercise restrained excess pro-inflammatory cytokine expression but increased anti-inflammatory cytokine level in a rib retraction model. [ABSTRACT FROM AUTHOR]

While considerable effort has been made to investigate the neural mechanisms of pain, much less effort has been devoted to itch, at least until recently. However, itch is now gaining increasing recognition as a widespread and costly medical and socioeconomic issue. This is accompanied by increasing interest in the underlying neural mechanisms of itch, which has become a vibrant and rapidly-advancing field of research. The goal of the present forefront review is to describe the recent progress that has been made in our understanding of itch mechanisms.

In the present study, we demonstrated that there is a direct relationship between scratching behaviors induced by itch and functional changes in the brain reward system. Using a conditional place preference test, the rewarding effect was clearly evoked by scratching under both acute and chronic itch stimuli. The induction of ΔFosB, a member of the Fos family of transcription factors, was observed in dopamine transporter (DAT)-positive dopamine neurons in the ventral tegmental area (VTA) of mice suffering from a chronic itch sensation. Based on a cellular analysis of scratching-activated neurons, these neurons highly expressed tyrosine hydroxylase (TH) and DAT genes in the VTA. Furthermore, in an in vivo microdialysis study, the levels of extracellular dopamine in the nucleus accumbens (NAcc) were significantly increased by transient scratching behaviors. To specifically suppress the mesolimbic dopaminergic pathway using pharmacogenetics, we used the TH-cre/hM4Di mice. Pharmacogenetic suppression of mesolimbic dopaminergic neurons significantly decreased scratching behaviors. Under the itch condition with scratching behaviors restricted by an Elizabethan collar, the induction of ΔFosB was found mostly in corticotropin-releasing hormone (CRH)-containing neurons of the hypothalamic paraventricular nucleus (PVN). These findings suggest that repetitive abnormal scratching behaviors under acute and chronic itch stimuli may activate mesolimbic dopamine neurons along with pleasant emotions, while the restriction of such scratching behaviors may initially induce the activation of PVN-CRH neurons associated with stress. Image 1 • The rewarding effect can be evoked by scratching under itch stimuli. • Pharmacogenetic suppression of dopaminergic neurons decreases scratching. • Scratching under itch stimuli activates mesolimbic dopamine neurons. • The restriction of scratching activates PVN-CRH neurons. [ABSTRACT FROM AUTHOR]

An itch is defined as an unpleasant sensation that evokes a desire to scratch. Glutamate is a major excitatory neurotransmitter in the mammalian central nervous system and has a crucial role in pruriceptive processing in the spinal dorsal horn. It is well known that glutamate exerts its effects by binding to various glutamate receptors including α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, and that AMPA/kainate receptors play a crucial role in pruriceptive processing; however, the precise role of AMPA receptors remains uncertain. Perampanel, an antiepileptic drug, is an antagonist of AMPA receptors. Pretreatment with perampanel dose-dependently attenuated the induction of scratching, a behavior typically associated with pruritus, by intradermal administration of the pruritogen chloroquine. In addition, the induction of scratching in mice painted with diphenylcyclopropenone and NC/Nga mice treated with Biostir AD, animal models of contact dermatitis and atopic dermatitis, respectively, was dose-dependently alleviated by administration of perampanel. These findings indicate that AMPA receptors play a crucial role in pruriceptive processing in mice with acute or chronic pruritus. • Perampanel is an AMPA receptor antagonist that has antipruritic effects. • Administration of perampanel attenuates scratches induced by chloroquine, but not histamine. • Perampanel ameliorates chronic pruritus induced by diphenylcyclopropenone painting. • Perampanel alleviates chronic pruritus in an atopic dermatitis mouse model. [ABSTRACT FROM AUTHOR]

• The calcium activity of Po was increased during facial histamine-induced scratching. • Pharmacogenetic inhibition of Po suppressed facial histamine-induced scratching. • Dissection of the brain areas innervating Po through retrograde virus tracing. Itch induces a desire to scratch and leads to skin damage in some severe conditions. Much progress has been made in the peripheral and spinal level, and recent findings suggested that we need to focus on the central circuitry mechanism. However, the functional role of the thalamus in itch signal processing remains largely unknown. We showed that the posterior thalamic nucleus (Po) played a vital role in modulating facial histaminergic itch signal processing. We found that the calcium signal of Po neurons was increased during the histaminergic itch-induced scratching behavior in the cheek model, and pharmacogenetic suppression of Po neurons reduced the scratching behaviors. Retrograde mapping results suggested that the Po receives information from the somatosensory cortex, motor cortex, parabrachial nucleus (PBN), the principal sensory trigeminal nucleus (PrV) and the spinal trigeminal nucleus (SpV), which participate in itch signal transmission from head and body. Thus, our study indicates that the Po is critical in modulating facial histaminergic itch signal processing. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to determine kitten preferences towards different scratchers and the effects of catnip and cat odor on kitten scratching behaviors. Methods: Two-choice preference tests were conducted to compare scratchers and preferred scratchers with or without additives (ie, catnip, catnip oil, cat hair) in six studies. Kittens (n = 40, <8 weeks old) had access to two scratchers on the floor of a simulated living room for 20 mins and interactions were video-recorded. The time each kitten spent scratching each scratcher was compared. Results: In study 1, the S-shaped cardboard was preferred over a hemp post with a toy on top, and no difference was observed in the other pairs of scratchers compared. In study 2, the S-shaped cardboard was preferred by kittens compared with a raised scratcher covered with window screen or with carpet, and no differences were observed between the latter two scratchers. In study 3, the scratcher covered with window screen set upright was preferred over the same scratcher laid horizontally on the floor. The S-shaped cardboard was preferred over the scratcher covered with bubble wrap. In study 4, kittens preferred the S-shaped cardboard over the scratchers covered with window screen or short-fiber carpet but not over the scratcher covered with long-fiber carpet. In study 5, the S-shaped cardboard was strongly preferred over the long cardboard and rectangular cardboard but not over the boat-shaped cardboard. In study 6, dried catnip plant, catnip oil spray or the hair from other cats did not alter the scratching behavior exhibited by the kittens vs the control S-shaped cardboard alone. Conclusions and relevance: The S-shaped cardboard scratcher was a preferred scratcher for kittens. Catnip or odor of other cats did not alter this behavior in kittens. S-shaped cardboard may be a preferred scratching device for kittens. [ABSTRACT FROM AUTHOR]

Practical relevance: While scratching is a normal, beneficial behavior for cats, it can create problems when cats scratch objects owners deem as inappropriate. However, if veterinarians make suitable recommendations from the first veterinary visit, owners will be able to implement effective preventive strategies to develop good scratching patterns for life. Educating owners as to why cats scratch, how to guide cats to scratch only on desirable surfaces (ie, a scratching post), which types of scratching posts are preferred by most cats, the benefits of pheromone products, as well as other strategies to avoid destructive scratching, helps to preserve the cat–owner bond and reduces the risk of relinquishment. Clinical challenges: Clients may not directly ask veterinarians for their assistance regarding their cat's destructive scratching, and may not be aware that anything can be done except for declawing their cat. Evidence base: Published studies on scratching are limited. Destructive scratching has been documented as a reason for the relinquishment of cats to shelters and the negative effects of declaw surgeries are being increasingly discovered. Among recent scientific publications are studies assessing kitten and cat preferences for scratching substrates, and the use of pheromones to encourage appropriate scratching behavior. This review draws on these studies, among other resources, as well as the authors' personal experiences. [ABSTRACT FROM AUTHOR]

Objectives: This study was conducted to clarify the effects of agarwood on histamine release from mast cells in rats and on the scratching behaviors in mice. Methods: Histamine release from rat mast cells induced by compound 48/80 or concanavalin A (Con A) and compound 48/80-induced scratching behavior in mice were examined to investigate

Pruritus, including neuropathic and psychogenic pruritus, is an unpleasant feeling that causes a desire to scratch, which negatively impacts physical and psychological aspects of daily life. Nonetheless, little is known about the neural mechanisms involved in pruritus. Glutamate is a predominant excitatory neurotransmitter in the mammalian central nervous system and exerts its effects by binding to various glutamate receptors, including kainate (KA) receptors; however, the precise involvement of each glutamate receptor in pruriceptive processing remains unclear, particularly that of KA receptors. Therefore, the roles of KA receptors in histamine-dependent and -independent itch were investigated using CNQX, an AMPA/KA receptors antagonist, UBP310 and UBP302, antagonists of KA receptors, and small interfering (si)RNAs against KA receptor subunits in mice with acute and chronic pruritus. The effects of KA receptor antagonists on histamine-induced c-Fos expression in the spinal cord were also examined. The intrathecal administration of CNQX reduced the number of scratching events induced by histamine and chloroquine. On the other hand, UBP310 or UBP302 and the siRNAs of KA receptor subunits 1–3 significantly inhibited the induction of scratching events in mice treated with histamine, while no significant change was observed in the induction of spontaneous scratching events in mice with chronic pruritus. In addition, antagonists of KA receptors attenuated c-Fos expression in the superficial layers of the dorsal horn induced by histamine. These results indicate that KA receptors are involved in acute pruriceptive processing in the spinal cord induced by histamine, but not chloroquine or chronic itch. • CNQX attenuates scratching events induced by histamine and chloroquine (CQ). • UBP310 and UBP302 inhibit the induction of scratching by histamine, but not CQ. • UBP310 and UBP302 reduce c-Fos expression by histamine, but not CQ. • Histamine-induced scratches are attenuated by GluK1-3 siRNAs, but not GluK4-5 siRNAs. [ABSTRACT FROM AUTHOR]

Perilla (Perilla frutescens L.) leaves have shown therapeutic efficacy in the treatment of inflammatory disorders, allergies, bronchial asthma, and systemic damage due to free radicals. In the present study we analyzed the active constituents in perilla leaves using high-performance liquid chromatography (HPLC) and isolated luteolin, a polyphenolic flavonoid. We investigated the anti-inflammatory and antipruritic properties of luteolin. Luteolin inhibited the secretion of inflammatory cytokines such as interleukin-1β (IL-1 β) and tumor necrosis factor-α (TNF-α) from human mast cells (HMC-1) stimulated with phorbol myristate acetate plus calcium ionophore A23187 in a dose-dependent manner. Luteolin also significantly reduced the histamine release from rat peritoneal mast cells stimulated by compound 48/80, a potent histamine liberator. Furthermore, the administration of luteolin markedly inhibited the scratching behavior and vascular permeability induced by pruritogens, such as compound 48/80 or serotonin, in ICR mice. These results suggested that luteolin has potential as a therapeutic agent against inflammation and itch-related skin diseases.

Objective:In this study, we aimed to study the effects of ICI204,448, naloxone methiodide and levocetirizine on the scratching behavior induced by intradermal injection of a ?-opioid antagonist, nor-binaltorphimine (nor-BNI), into the rostral back of ICR mice were investigated. Materials and methods:Male ICR mice weighing 30?35 g were used. The number of scratching episodes were counted for 60 min after i.d. injection of nor-BNI. Results:nor-BNI dose dependently increased in the number of scratching episodes in ICR mice. nor-BNI-induced scratching behavior was inhibited by not only nalfurafine but also ICI204,448, a peripherally selective ?-opioid agonist. Naloxone and naloxone methiodide, a peripherally restricted ?-opioid antagonist, also inhibited nor-BNI-induced scratching behavior. Scratching behavior induced by nor-BNI was inhibited by chlorpheniramine as well as levocetirizine, a third-generation H1antagonist that does not cross into the CNS. Conclusion:These results suggest that scratching behavior induced by this ?-opioid antagonist, nor-BNI, is related to not only central but also peripheral opioid and H1receptors. [ABSTRACT FROM PUBLISHER]

Cynanchum atratum Bunge (Apocynaceae) is a folk medicine to treat skin inflammatory diseases. However, the effects of C. atratum on atopic dermatitis have not been elucidated. In this study, we evaluate the effects of aqueous extract of C. atratum (CA) and its molecular mechanism on atopic dermatitis (AD). 1 and 100 mg/mL CA were topically applied to 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions for 11 days. The number of scratching behavior was evaluated for 20 min. AD-like symptoms including elevated serum IgE, skin hyperplasia and mast cell infiltration were investigated. The expressions of pro-inflammatory cytokines and mediators were analyzed in AD-like skin legions. In addition, pro-inflammatory cytokine production was confirmed in human mast cells (HMC)-1 stimulated with PMA plus A23187 (PMACI). Topical application of CA attenuated total serum IgE level and scratching behavior. Skin hyperplasia including epidermis and dermis was ameliorated in CA-treated skin legions. The number of infiltrated mast cells was significantly decreased by CA treatment. In addition, CA reduced pro-inflammatory cytokines, such as IL-6, IL-1β and TNF-α and Th2 cytokine, IL-4, in both of AD-like skin lesions and PMACI-sensitized HMC-1 cells. Furthermore, CA decreased the expressions of NF-κB, phospho-IκBα and MAP kinase. These results suggest the inhibitory effects of CA on the development of AD by regulating pro-inflammatory cytokines and mediators. CA could be an effective substance for the treatment of AD. [ABSTRACT FROM AUTHOR]

Atopic dermatitis, a chronic relapsing and pruritic inflammation of the skin also thought to be involved in, or caused by immune system destruction is an upsetting health problem due to its continuously increasing incidence especially in developed countries. Mast cell infiltration in atopic dermatitis skin lesions and its IgE-mediated activation releases various cytokines and chemokines that have been implicated in the pathogenesis of atopic dermatitis. This study was aimed at investigating synergistic anti-inflammatory, anti-pruritic and anti-atopic dermatitis effects of Diospyros lotus leaf extract (DLE) and Muscat bailey A grapefruit stem extract (GFSE) in atopic dermatitis-like induced skin lesions in mice. Combinations of DLE and GFSE inhibited TNF-α and IL-6 production more than DLE or GFSE in PMA plus calcium ionophore A23187-activated HMC-1 cells. DLE and GFSE synergistically inhibited compound 48/80-induced dermal infiltration of mast cells and reduced scratching behavior than DLE or GFSE. Furthermore, DLE and GFSE synergistically showed a stronger ameliorative effect in skin lesions by reducing clinical scores; dermal infiltration of mast cells; ear and dorsal skin thickness; serum IgE and IL-4 production in atopic dermatitis-like mice. Collectively, these results suggest that DLE and GFSE synergistically exhibit anti-atopic dermatitis effects in atopic dermatitis-like skin lesions in mice. [ABSTRACT FROM AUTHOR]

The involvement of serotonin (5-HT) and/or noradrenaline in acute pruriceptive processing in the central nervous system (CNS) has been reported using antidepressants, such as milnacipran, a serotonin and noradrenaline reuptake inhibitor, and mirtazapine, a noradrenergic and specific serotonergic antidepressant; however, the roles of 5-HT receptor family in acute pruriceptive processing have not been fully elucidated in the CNS. In the present study, scratching behavior induced by chloroquine (CQ) was ameliorated by milnacipran or mirtazapine, and these effects were reversed by SB207266, a 5-HT 4 antagonist, or SB258585, a 5-HT 6 antagonist, but not by SB258585, a 5-HT 5 antagonist. Moreover, CQ-induced scratches were mitigated by intrathecal injection of 5-HT 4 agonists, such as BIMU8 and ML10302, and the 5-HT 6 agonist, WAY208466. Conversely, histamine-induced scratches were not affected by the 5-HT 4 agonists or a 5-HT 6 agonist. Similarly, the amelioration of histamine-induced scratches by these antidepressants was not reversed by the 5-HT 4 , 5-HT 5 , or 5-HT 6 receptor antagonist. Therefore, 5-HT is involved in the amelioration of CQ-induced scratches by milnacipran and mirtazapine, and 5-HT 4 , 5-HT 5 , and 5-HT 6 receptors play differential roles in acute pruriceptive processing after administration of CQ or histamine.

Hemokinin-1 (HK-1) and endokinins are peptides predicted from a new mammalian tachykinin gene, TAC4. The amino acid sequences derived from rat/mouse HK-1 and human HK-1 are not identical; however, the effects induced by intracerebroventricular or intrathecal administration of HK-1 are attenuated by treatment with antagonists of neurokinin 1 (NK1) receptor, substance P (SP) receptor, indicating that HK-1 is an agonist of the NK1 receptor. On the other hand, a growing body of evidence indicates that pharmacological characteristics of HK-1 and SP are always not identical, suggesting that the HK-1-preferred receptor may be involved in the effects of HK-1. Endokinins are derived from human TAC4 and consist of four endokinins, endokinin A (EKA), endokinin B (EKB), endokinin C (EKC) and endokinin D (EKD). Effects induced by intrathecal administration of EKA/B (the common C-terminal decapeptide in EKA and EKB) and SP were very similar, while the effects of SP and EKA/B were inhibited by EKC/D (the common C-terminal duodecapeptide in EKC and EKD). This inhibitory effect of EKC/D was derived from leucine at the carboxyl-terminus. These findings suggest that HK-1 and EKA/B have an agonistic effect, while EKC/D has an antagonistic effect on the NK1 receptor in nociceptive processing.

We report a case of 7-year-old monozygotic twin patients with atopic dermatitis. The HLA haplotypes were HLA A2, A11, B27, B61, DR1, and DR4. Both serum IgE levels and cedar pollen radioallergosorbent test (RAST) scores were high in the twins (elder/younger sister: IgE: 5170/3980 IU/ml and Japansese cedar pollen: >100/64.0) in contrast to low mite and food RAST scores (Dermatophagoides Pterygonium; 0.59/0.4 and egg white 9.24/4.6). The patients showed positive immediate (20 min in both sisters) and delayed (24 hours in elder sister, 24, 48, 72 hours in younger sister) reactions to a scratch test with Japanese cedar pollen. Skin lesions on the face were aggravated and extended to the trunk and extremities during the Japanese cedar pollen season and gradually subsided in summer. Oral provocation with egg white or cow milk showed no exacerbations, and topical corticosteroid did not improve the eczema. In contrast, successful protection from severe scratching behaviors was achieved by use of topical anti-allergic eye drops and wearing nightgowns made by the mother.

Article commented: Kremer AE, Martens JJ, Kulik W, Rueff F, Kui-per EM, van Buuren HR, van Erpecum KJ, Kon-drackiene J, Prieto J, Rust C, Geenes VL, Williamson C, Moolenaar WH, Beuers U, Oude El-ferink RP. Lysophosphatidic acid is a potential mediator of cholestatic pruritus. Gastroenterology 2010; 139:1008-18. Original Abstract: Background & aims. Pruritus is a common and disabling symptom in cholestatic disorders. However, its causes remain unknown. We hypothesized that potential pruritogens accumulate in the circulation of cholestatic patients and activate sensory neurons. Methods. Cytosolic free calcium ([Ca(2+)] (i)) was measured in neuronal cell lines by ratiometric fluorometry upon exposure to serum samples from pruritic patients with intrahepatic cholestasis of pregnancy (ICP), primary biliary cirrhosis (PBC), other cholestatic disorders, and pregnant, healthy, and nonpruritic disease controls. Putative [Ca(2+)] (i)-inducing factors in pruritic serum were explored by analytical techniques, including quantification by high-performance liquid chromatography/mass spectroscopy. In mice, scratch activity after intradermal pruritogen injection was quantified using a magnetic device. Results. Transient increases in neuronal [Ca(2+)] (i) induced by pruritic PBC and ICP sera were higher than corresponding controls. Lysophosphatidic acid (LPA) could be identified as a major [Ca(2+)] (i) agonist in pruritic sera, and LPA concentrations were increased in cholestatic patients with pruritus. LPA injected intradermally into mice induced scratch responses. Autotaxin, the serum enzyme converting lysophosphatidylcholine into LPA, was markedly increased in patients with ICP vs. pregnant controls (P < 0.0001) and cholestatic patients with vs. without pruritus (P < 0.0001). Autotaxin activity correlated with intensity of pruritus (P < 0.0001), which was not the case for serum bile salts, histamine, tryptase, substance P, or mu-opioids. In patients with PBC who underwent temporary nasobiliary drainage, both itch intensity and autotaxin activity markedly decreased during drainage and returned to preexistent levels after drain removal. Conclusions. We suggest that LPA and autotaxin play a critical role in cholesta-tic pruritus and may serve as potential targets for future therapeutic interventions.

In this study, we examined the interaction between histamine H 1 receptor and μ-opioid receptor in scratching behavior in ICR mice. Both histamine and morphine caused scratching and simultaneous injection of histamine and morphine had an additive effect. Chlorpheniramine and naloxone inhibited histamine-induced scratching behavior. These two drugs also inhibited morphine-induced scratching behavior. Simultaneous injection of chlorpheniramine and naloxone caused a significant inhibition of histamine-induced scratching compared with separate injections. The same findings were also noted for morphine-induced scratching. These results strongly indicate a close relationship between histamine H 1 receptor and μ-opioid receptor in scratching behavior in ICR mice. [ABSTRACT FROM AUTHOR]

Skin is recognized as the boundary between an individual and society. Skin is also known to impact social and psychiatric conditions. The social aspect of skin characteristics has been gaining attention especially when it comes to hair-pulling or skin-picking disorders. These disorders, which target skin, hair or nails, have been investigated and described in the revised version of DSM-5 as “body-focused repetitive behaviors” (BFRB). Most patients with BFRB have psychiatric problems. However, most will visit a dermatologist, and not a psychiatrist, although the psychiatric symptoms and recurrent BFRBs are difficult to manage for dermatologists who do not typically have psychiatric knowledge. The untreated psychiatric symptoms, including targeting of the skin, will eventually result in skin damage such as lesions, infection, and scars. DSM-5-revised describes a new categorization of obsessive-compulsive and related disorders (OCRDs). Hair-pulling disorder known as trichotillomania is now categorized as an OCRD, whereas it was previously recognized as an impulse-control disorder under DSM-IV. Additionally, excoriation (skin-picking) disorder and body-focused repetitive be- havior disorder, recognized as a new unit in diagnosis, have also been categorized as OC-RDs. These revisions in diagnostic criteria reflect significance of the close relationships between BFRB and OCRDs, as well as the importance of psychosomatic dermatology and psychodermatology, which examine the clinical relationships between dermatology and psychiatry. This study reviews literature that is relevant to hair-pulling and skin-picking disorders, as well as scratching behavior, especially that which occurs in patients with atopic dermatitis (AD). The paper also investigates the clinical characteristics and treatment of a patient with hair-pulling disorder and AD treated in a child psychiatry clinic, demonstrating the benefits of placing greater focus on psychodermatology, and the importance of collaboration between child psychiatrists and dermatologists. [ABSTRACT FROM AUTHOR]

Since anticonvulsants have been used for treating neuralgias, an interest has arisen to experimentally test vigabatrin for its gabaergic mechanism of action. For this, 41 Wistar rats were used, and in 25 of them a constrictive sciatic neuropathy was induced (Bennet & Xie model). For testing pain symptoms, spontaneous (scratching) and evoked behaviors to noxious (46o C) and non-noxious (40o C) thermal stimuli were quantified. Moreover, a comparative pharmacological study of vigabatrin with other analgesic anticonvulsant drugs was also performed. The results showed a possible dose-dependent analgesic effect of vigabatrin (gamma-vinyl-GABA) on experimental neuropathic pain, as shown by the significant (p

Scratching behavior observed after epicutaneous challenge with the antigen 2,4-dinitrofluorobenzene (DNFB) in the ear of BALB/c mice passively sensitized with anti-dinitrophenol (DNP). Immunoglobulin (Ig) E was characterized pharmacologically and compared with that caused by compound 48/80. Although DNFB application itself caused scratching behavior in non-sensitized mice, the number of scratchings apparently increased in sensitized mice from 60 min after antigen application in comparison with non-sensitized control mice. Prednisolone, cyproheptadine, dibucaine and naloxone significantly inhibited the DNFB-induced scratching behavior, whereas the histamine H1-receptor antagonists HSR-609, cetirizine and terfenadine only showed a tendency to inhibit scratching. Injection of 48/80 into the rostral part of the back also caused scratching. The first scratching was observed within 10 min after injection and lasted intermittently for 30 min. The 48/80-induced scratching was markedly inhibited by cyproheptadine, dibucaine and naloxone, but not by prednisolone and the histamine H1-receptor antagonists. Ear edema caused by DNFB application in sensitized mice was markedly inhibited by prednisolone, HSR-609, cetirizine, terfenadine and cyproheptadine, whereas dibucaine and naloxone failed to affect ear edema. These results indicate that scratching behavior could be induced in mice in association with an IgE-mediated allergic cutaneous reaction and that the reaction is pharmacologically similar, but not identical, to that caused by 48/80. Although histamine is considered to participate in the formation of ear edema, it may not play an important role in the generation of scratching.

• Vibration-assisted scratching effectively decreases total force compared to conventional scratching. • Increase in amplitude and frequency leads to the reduction in total force, which is beneficial for scratching. • Increasing frequency causes an increase in scratched zone temperature, which has a positive effect on machining. • The scratching with a large vibration amplitude and frequency can remove more material. Although vibration-assisted scratching achieves higher machining efficiency than conventional scratching, its microstructural behavior is still unclear. In the present work, the deformation behavior and microstructural growth of monocrystalline CoCrFeNiCu high-entropy alloy during the vibration-assisted scratching through molecular dynamics simulation are investigated. The expected result shows that the vibration-assisted scratching effectively decreases the total force compared to the conventional scratching. The increase in the vibration amplitude and frequency leads to the reduction in the total force, which is advantageous in scratching. The shear strain concentration region in vibration-assisted scratching is larger than that of conventional scratching due to the expansion of the scratched area. Besides, the increase in vibration amplitude and frequency leads to a corresponding increase in shear strain and residual stress. The vibration-assisted scratching produces a larger high-temperature zone than the conventional scratching, and the increase of vibration frequency also results in an increase in the scratched zone temperature, which has a positive effect on easier machining. The microstructure evolution shows that Shockley partial dislocations account for the majority of the total dislocations. Moreover, the scratching with a large vibration amplitude and frequency removes more material. Therefore, insights into scratching behavior at the atomic level can aid in the optimization of the vibration-assisted machining process. The figure shows the simulation model (a), average force (b), surface morphologies (c). [Display omitted] [ABSTRACT FROM AUTHOR]

The present study investigated the effects of pharmacological spinal inhibition of voltage-gated calcium channels (VGCC) in mouse pruritus. The epidural administration of P/Q-type MVIIC or PhTx3.3, L-type verapamil, T-type NNC 55-0396 or R-type SNX-482 VGCC blockers failed to alter the scratching behavior caused by the proteinase-activated receptor 2 (PAR-2) activator trypsin, injected into the mouse nape skin. Otherwise, trypsin-elicited pruritus was markedly reduced by the spinal administration of preferential N-type VGCC inhibitors MVIIA and Phα1β. Time-course experiments revealed that Conus magus -derived toxin MVIIA displayed significant effects when dosed from 1 h to 4 h before trypsin, while the anti-pruritic effects of Phα1β from Phoneutria nigriventer remained significant for up to 12 h. In addition to reducing trypsin-evoked itching, MVIIA or Phα1β also prevented the itching elicited by intradermal (i.d.) injection of SLIGRL-NH2, compound 48/80 or chloroquine, although they did not affect H 2 O 2 -induced scratching behavior. Furthermore, the co-administration of MVIIA or Phα1β markedly inhibited the pruritus caused by the spinal injection of gastrin-releasing peptide (GRP), but not morphine. Notably, the epidural administration of MVIIA or Phα1β greatly prevented the chronic pruritus allied to dry skin model. However, either tested toxin failed to alter the edema formation or neutrophil influx caused by trypsin, whereas they significantly reduced the c-Fos activation in laminas I, II and III of the spinal cord. Our data bring novel evidence on itching transmission mechanisms, pointing out the therapeutic relevance of N-type VGCC inhibitors to control refractory pruritus. [ABSTRACT FROM AUTHOR]

The article discusses the result of nodakenin, a significant natural resource and anti-allergic and anti-inflammatory medicinal material on atopic dermatitis-like skin lesions. It states the investigation of inhibitory effect of nodakenin on 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD)-like skin lesions in imprinting control region (ICR) mice. An overview on the study involving the animal care conducted in the Yonsei University at Wonju, South Korea is also presented.

Contact dermatitis (CD) is a pattern of inflammatory responses in the skin that occurs through contact with external factors. The clinical picture is a polymorphic pattern of skin inflammation characterized by a wide range of clinical features, including itching, redness, scaling, and erythema. Coriandrum sativum L. (CS), commonly known as coriander, is a member of the Apiaceae family and is cultivated throughout the world for its nutritional and culinary values. Linoleic acid and linolenic acid in CS have various pharmacological activities. However, no study of the inhibitory effects of CS on CD has been reported. In this study, we demonstrated the protective effect of CS against 2,4-dinitrochlorobenzene-induced CD-like skin lesions. CS, at doses of 0.5-1%, applied to the dorsal skin inhibited the development of CD-like skin lesions. Moreover, the Th2-mediated inflammatory cytokines, immunoglobulin E, tumor necrosis factor-α, interferon-γ, interleukin (IL)-1, IL-4, and IL-13, were significantly reduced. In addition, CS increased the levels of total glutathione and heme oxygenase-1 protein. Thus, CS can inhibit the development of CD-like skin lesions in mice by regulating immune mediators and may be an effective alternative therapy for contact diseases. [ABSTRACT FROM AUTHOR]

Abstract: Allergic dermatitis among common skin diseases is a chronic and recurrent inflammatory skin disorder caused by genetic, environmental, allergens as well as microbial factors. Allergic dermatitis patients clinically present skin erythematous plaques, eruption, elevated serum immunoglobulin E (IgE) and T helper cell type 2 (Th2) cytokine levels. The leaf of walnut tree Juglans mandshurica Maxim (JM) is consumed food and traditional phytomedicine in Asia, China, Siberia and Korea. JM has been reported to have various pharmacological activities, such as anti-tumor, anti-oxidative, and anti-bacterial effects. However, no study of the inhibitory effects of JM on allergic dermatitis has been reported. Here, we demonstrated the effect of JM against 2,4-dinitrochlorobenzene-induced allergic dermatitis-like skin lesions. 0.5% JM or 1% dexamethasone (positive control) applied to the dorsal skin inhibited development of allergic dermatitis-like skin lesions and scratching behavior. Moreover, the Th2-mediated inflammatory cytokines IgE, tumor necrosis factor-α, interleukin (IL)-1, and IL-13, were significantly reduced by JM treatment. Thus JM can inhibit development of allergic dermatitis-like skin lesions in mice by regulating immune mediators, and may be an effective alternative therapy for allergic dermatitis. [Copyright &y& Elsevier]

Abstract: Aims: Pruritus is a common symptom of skin diseases, and is associated with impaired sleep quality and a considerable reduction in the patient's quality of life. Recently, it was reported that there are sex-specific differences in scratching behavior in chronic pruritus patients. Namely, female chronic pruritus patients scratch more and have significantly more scratch lesions than male patients. However, few animal studies have examined sex-related differences in scratching behavior. Thus, the present work investigated sex-related differences in animal pruritus using pruritogens, which are often used to create experimental animal models of itching. Main methods: Acute pruritus was induced in ICR mice by a single intradermal injection of histamine, 4-methylhistamine, serotonin, compound 48/80, substance P (SP), or the proteinase-activated receptor-2 (PAR-2)-activating peptide SLIGRL-NH2. Chronic pruritus was induced by 5weeks of the repeated application of 2,4,6-trinitro-1-chlorobenzene (TNCB) to BALB/c mice. Key findings: Female mice showed significantly higher scratching counts in SLIGRL-NH2-induced pruritus than male mice. Conversely, there was no obvious sex-related difference in scratching behavior for the other pruritogens examined. Significance: These results indicate that sex-related differences may exist in the pruritogen-responsive neurons that transmit the itch signal induced by SLIGRL-NH2, but not by histamine or 5-HT. [Copyright &y& Elsevier]

Summary: Hemokinin-1 (HK-1) and endokinins are peptides predicted from a new mammalian tachykinin gene, TAC4. The amino acid sequences derived from rat/mouse HK-1 and human HK-1 are not identical; however, the effects induced by intracerebroventricular or intrathecal administration of HK-1 are attenuated by treatment with antagonists of neurokinin 1 (NK1) receptor, substance P (SP) receptor, indicating that HK-1 is an agonist of the NK1 receptor. On the other hand, a growing body of evidence indicates that pharmacological characteristics of HK-1 and SP are always not identical, suggesting that the HK-1-preferred receptor may be involved in the effects of HK-1. Endokinins are derived from human TAC4 and consist of four endokinins, endokinin A (EKA), endokinin B (EKB), endokinin C (EKC) and endokinin D (EKD). Effects induced by intrathecal administration of EKA/B (the common C-terminal decapeptide in EKA and EKB) and SP were very similar, while the effects of SP and EKA/B were inhibited by EKC/D (the common C-terminal duodecapeptide in EKC and EKD). This inhibitory effect of EKC/D was derived from leucine at the carboxyl-terminus. These findings suggest that HK-1 and EKA/B have an agonistic effect, while EKC/D has an antagonistic effect on the NK1 receptor in nociceptive processing. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: The root of Panax ginseng CA Meyer (ginseng) has been used for diabetes, cancer, stress and allergic diseases in the traditional Chinese medicine. Aim of the study: To understand the role of intestinal microflora in the pharmacological effect of ginsenoside Re, which is a main constituent of ginseng, we investigated its anti-scratching behavioral effect in the mice treated with or without antibiotics. Materials and methods: Ginsenoside Re was orally administered to the mice treated with antibiotics (cefadroxil, oxytetracycline and erythromycin mixture (COE), streptomycin or/and tetracycline) and then investigated the relationship between ginsenoside Re-metabolizing β-glucosidase and α-rhamnosidase activities of intestinal microflora and its antiscratching behavioral effect. The anti-scratching behavioral effects of ginsenosides were investigated in the increments of 1h and 6h after their oral administrations. The scratching behavioral frequency was measured for 1h after treatment with histamine. Results: Ginsenoside Re inhibited histamine-induced scratching behavior in mice. The anti-scratching behavioral effect of ginsenoside Re was more potent 6h after its oral administration than 1h after. However, its inhibitory effect was significantly attenuated in mice treated with COE, but it nearly was not affected in mice treated with streptomycin and/or tetracycline. Treatment with COE also significantly lowered fecal ginsenoside Re-metabolizing β-glucosidase and α-rhamnosidase activities in mice, as well as fecal metabolic activity of ginsenoside Re to ginsenoside Rh1. The anti-scratching behavioral effect of ginsenoside Rh1, a metabolite of ginsenoside Re by intestinal microflora, was superior to that of ginsenoside Re. Ginsenoside Rh1 potently inhibited the expression of IL-4 and TNF-α, as well as the activation of NF-κB and c-jun activation in histamine-stimulated scratching behavioral mice. Conclusion: Ginsenoside Re may be metabolized to ginsenoside Rh1 by intestinal microflora, which enhances its anti-scratching behavioral effect by inhibiting NF-κB and c-jun activations. [Copyright &y& Elsevier]

Lactobacillus plantarum K-1 (LP) inhibiting AP-1 (c-Jun) and NF-κB activations was isolated from kimchi, and its inhibitory activity against scratching behavior and passive cutaneous anaphylaxis reaction in mice was investigated. Heat-inactivated LP (heated at 60°C for 30 min) potently inhibited the expression of TNF-α and IL-4 as well as the activation of their transcription factors, NF-κB and c-jun, in phorbol 12′-myristate 13′-acetate-stimulated RBL-2H3 cells. LP (1 ×10 CFU per mouse) showed a potent inhibition against passive cutaneous anaphylaxis reaction induced by the IgE-antigen complex in mice, inhibiting it by 87.5%. LP (1 × 10 CFU/mouse) inhibited histamine-induced scratching behavior by 58.9% compared to the control group. LP significantly inhibited vascular permeability induced by histamine. The inhibitory activity of LP against vascular permeability was in proportion to its inhibition against scratching behavior. LP potently inhibited histamine-induced cytokine production: it (1 × 10 CFU per mouse) inhibited IL-4, IL-1β, and TNF-α expression by 88.9%, 88.6%, and 98.9%, respectively. LP also inhibited IgE level increased by histamine by 85.3%. It inhibited histamine-induced the activations of their transcription factors, NF-κB and c-Jun. Based on these findings, LP may improve allergic diseases, such as anaphylaxis, atopic dermatitis, rhinitis, and pruritus by inhibiting the expression of IgE-switching cytokine IL-4 and proinflammatory cytokines IL-1β and TNF-α via NF-κB and AP-1 signaling pathways. [ABSTRACT FROM AUTHOR]

Abstract: The contribution of tachykinin neurokinin 1 (NK1) receptor to nociceptive processing in the dorsal horn has been evaluated by tachykinin NK1 receptor antagonism and knockout or knockdown of tachykinin NK1 receptor; however, these results have not always been consistent. Therefore, to reevaluate the role of tachykinin NK1 receptor in the dorsal horn, a solution of hemagglutinating virus of the Japan envelope (HVJ-E) with small interfering RNA (siRNA) against tachykinin NK1 receptor was administered intrathecally and then the effect of treatment on tachykinin NK1 receptor immunohistochemistry and on the induction of inflammation, thermal hyperalgesia and scratching behavior was evaluated. This treatment resulted in marked reduction of tachykinin NK1 receptor immunoreactivity through the spinal dorsal horn, and the induction of thermal hyperalgesia and scratching behavior by substance P was significantly attenuated in rats with tachykinin NK1 receptor siRNA. In addition, only one intrathecal injection of tachykinin NK1 receptor siRNA reduced carrageenan-induced inflammation and thermal hyperalgesia significantly and markedly attenuated the induction of flinching after formalin injection and c-Fos expression in the dorsal horn following formalin injection. The efficient down-regulation of tachykinin NK1 receptor by intrathecal administration tachykinin NK1 receptor siRNA suggests that this method may be a valuable tool for examining the function of genes expressed in the dorsal horn. [Copyright &y& Elsevier]

Abstract: Although glycyrrhetinic acid (GA) has been used for the prevention of itch in chronic dermatitis, the mechanism underlying the antipruritic effects of GA is still unclear. Recently, several mediators other than histamine, such as substance P and tryptase, were found to participate in chronic itch. Here, we investigated the effect of GA on pruritus induced by various pruritic agents including histamine in mice. We also determined the level of leukotriene (LT)B4 in mouse skin injected with substance P in an effort to uncover part of the antipruritic mechanism of GA. Scratching events were counted for 10min after intradermal injection of histamine, substance P (100nmol per site each), protease-activated receptor-2 (PAR-2) agonistic peptide (50nmol per site), or LTB4 (0.03nmol per site) with or without GA (4nmol per site) into male ICR mice. Levels of LTB4 in the skin after injection of substance P were determined by ELISA. GA did not suppress scratching behavior induced by histamine and LTB4, but markedly and dose-dependently suppressed that induced by substance P and PAR-2 agonistic peptide. LTB4 levels in skin elevated by substance P were lowered by GA. These data support the efficacy of GA in counteracting itch in chronic dermatitis because GA reduced scratching behavior induced by substance P and PAR-2 agonistic peptide. GA may exert antipruritic effects via inhibition of LTB4 production in skin. [Copyright &y& Elsevier]

Abstract: To clarify the mechanisms by which compound 48/80 (C48/80) induces scratching behavior, the involvement of dopamine D1 receptors was investigated. The intracisternal (i.t.) administration of SCH23390 (1.0μg), a selective dopamine D1 receptor antagonist, significantly decreased C48/80-induced scratching behavior in mice. These results suggest that dopamine D1 receptors contribute to scratching behavior or the itch sensation induced by subcutaneous injection of C48/80 in mice. Co-administration of SCH23390 and C48/80 enhanced c-fos immunoreactivities in the peduncular part of the lateral hypothalamus (PLH), whereas the immunoreactivities in the other groups were unchanged. The dopaminergic system may be playing an important role in the suppression of C48/80-induced scratching behavior by SCH23390. [Copyright &y& Elsevier]