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Sarcoptic mange is a parasitic disease causing severe pruritus, self-induced skin lesions and secondary infections. In many cases, an antipruritic treatment is useful to decrease clinical signs of the disease. Oclacitinib is a synthetic janus kinase-1 (JAK1) inhibitor, that selectively inhibits cytokines involved in inflammation and pruritus. The aim of this retrospective study was to evaluate efficacy of oclacitinib in alleviating pruritus and inflammation in dogs affected by scabies. Forty-four clinical records of dogs containing the words sarcoptes and oclacitinib were selected among dermatologic cases recorded within the last 5 years (2014-2019). Thirty-one of 44 cases with confirmed sarcoptic mange infestation were included. All dogs were treated at day (D)0 with systemic antiparasitic drugs (e.g. moxidectin, sarolaner, afoxolaner) in association with oclacitinib at 0.5 mg/kg by mouth every 12 hours for 14 days followed by oclacitinib administration every 24 hours for another 14 days. Visual Analogic Scale (VAS) was recorded at D0 and D30. Selected cases were 16 females and 15 males, median age was 4.5 years, majority were crossbred dogs. Mean VAS recorded at D0 was nine, and after onemonth decreased to three. Telephone follow up information, collected seven days after discharge, reported a significative decrease in pruritus within 24 hours. Our results suggest that the association of oclacitinib inhibition of JAK1 dependent cytokines (allergic and inflammatory associated IL2, IL4, IL6, IL13 and pruritogenic associated IL31) with conventional antiparasitic treatment, may be useful to provide quick relief from pruritus and decrease inflammation in dogs with sarcoptic mange.

Psoriasis is a highly prevalent chronic dermatitis, characterized by widespread skin inflammation and spontaneous itch. Given the adverse reactions and drug dependence of current treatment, new drugs for psoriasis therapy are urgently needed. This study aims to explore the anti-psoriatic effects of thymol in imiquimod (IMQ) induced mice, and elucidate the potential mechanisms for its therapeutic activities. Thymol reduced the scratching behavior in IMQ mice, and activated Ca2+ response in cervical DRG neurons via TRPM8 channel. Also, thymol alleviated psoriasis-like skin lesions, and attenuated the enhanced infiltration of dermal neutrophils, dendritic cells (DCs) and Th17 cells. In addition, it reversed the upregulated expression of pro-inflammatory cytokines in the skin (TNF-α, IL-22, IL-23, IL-17A, IL-17F, IL-17C, IL-6, IL-1β and IFN-γ) and serum (TNF-α, IL-6, IL-1β, IL-17A and IFN-γ). Our results indicated that thymol can effectively ameliorate pruritus and the symptoms of psoriasis-like inflammation induced by IMQ, which makes it a promising drug for the treatment of psoriasis.

Post burn pruritus is a common distressing sequela of burn wounds. Empirical antipruritic treatment often fails to have a satisfactory outcome, as the mechanism of it has not been fully elucidated. The aim of this study was to evaluate the manifestation of transient receptor potential vanilloid 3 (TRPV3), transient receptor potential ankyrin 1 (TRPA1) and other related receptors in post burn pruritus. Sixty-five burn patients with (n = 40) or without (n = 25) pruritus were investigated, including skin biopsies. Keratinocytes and fibroblasts from skin biopsy samples were separated. Real time-PCR showed that mRNA of TRPV3 was significantly increased in keratinocytes from pruritic burn scars than in keratinocytes from non-pruritic burn scars. With TRPV3 activation, intracellular Ca2+ concentrations were more significantly increased in keratinocytes from pruritic burn scars than in those from non-pruritic ones. Additionally, mRNA and protein levels of protease-activated receptor 2 (PAR2) and neurokinin-1 receptor (NK1R) were also significantly increased in pruritic burn scars. In conclusion, we confirmed that TRPV3, PAR2, and NK1R were highly expressed in pruritic burn scars. These results may help determine a novel mechanism for post burn pruritus. This article is protected by copyright. All rights reserved.

Itch is a major indicator of psoriasis, but the underlying mechanisms behind this symptom are largely unknown. To investigate the neuronal mechanisms of psoriatic itch, we tested whether mice subjected to the imiquimod-induced psoriasis model exhibit itch-associated behaviors. Mice received daily topical applications of imiquimod to the rostral back skin for 7 days. Imiquimod-treated mice exhibited a significant increase in spontaneous scratching behavior directed to the treated area as well as touch-evoked scratching (alloknesis). To characterize this model, we measured the mRNA expression levels of pruritogens and itch-relevant receptors/channels using real-time reverse transcription PCR. The mRNA expression of MrgprA3, MrgprC11, and MrgprD decreased gradually over time in the dorsal root ganglion (DRG) cells. There was no significant change in the mRNA expression of TRPV1 or TRPA1 in DRG cells. TRPV4 mRNA expression was transiently increased in the DRG cells, whereas TRPM8 mRNA was significantly decreased. The mRNA expression levels of histidine decarboxylase and tryptophan hydroxylase 1, as well as the intensity of histamine and serotonin immunoreactivity, were transiently increased in the skin on day 2, returning to baseline by day 7. Histamine H1-receptor antagonists, chlorpheniramine and olopatadine, significantly inhibited spontaneous scratching on day 2, but not day 7. Neither chlorpheniramine nor olopatadine affected alloknesis on day 2 or day 7. These results may reflect the limited antipruritic effects of histamine H1-receptor antagonists on human psoriasis. The imiquimod-induced psoriasis model seems to be useful for the investigation of itch and its sensitization in psoriasis.

Psoriasis is a common chronic inflammatory disease with an incidence of about 0.5-3 %. Previously psoriasis was not primarily regarded to be associated with pruritus; however, this perception has changed in recent years. Meanwhile data conclusively show that between 64 and 97 % of patients report about pruritus that can be severe in a number of cases. Apart from suffering from psoriasis, the presence of pruritus causes additional stress and leads to a significant impairment of health-related quality of life. Neurogenic inflammation at least in part contributes to the development of pruritus in psoriasis skin lesions. A number of neuropeptides including substance P and calcitonin gene related peptide can act as pro-inflammatory mediators. There is evidence for a dysbalance between κ‑ and µ‑opioid receptors in lesional skin favoring inflammation and pruritus. After clearing of psoriasis lesions, pruritus is relieved as well. Therefore, specific treatment of pruritus is not necessary in general. In cases where severe pruritus is a prominent symptom, targeted therapy with mirtazapin or doxepin or neuroleptic compounds such as pregabalin or gabapentin or drugs affecting the κ‑ und µ‑opioid receptor balance can be administered. Today the importance of pruritus as a prominent symptom of psoriasis lesions has been widely accepted. In recent and running clinical trials with new drugs, pruritus at baseline and the effect of these drugs on pruritus is always assessed. This awareness also fuels basic research about pruritus in psoriasis.

The increase of endocannabinoid tonus by inhibiting fatty acid amide hydrolase (FAAH) or monoacylglycerol lipase (MAGL) represents a promising therapeutic approach in a variety of disease to overcome serious central side effects of exocannabinoids. Recent studies reported that systemic administration of FAAH and MAGL inhibitors produce antipruritic action. Dual FAAH/MAGL inhibitors have also been described to get enhanced endocannabinoid therapeutic effect. In this study, we examined and compared dose-related antipruritic effects of systemic (intraperitoneal; ip) or intrathecal (it) administration of selective FAAH inhibitor PF-3845 (5, 10, and 20 mg/kg, i.p.; 1, 5, and 10 µg, i.t.), MAGL inhibitor JZL184 (4, 20, and 40 mg/kg, i.p.; 1, 5, and 10 µg, i.t.) and dual FAAH/MAGL inhibitor JZL195 (2, 5, and 20 mg/kg, i.p.; 1, 5, and 10 µg, i.t.) on serotonin (5-HT)-induced scratching model. Serotonin (25 μg) was injected intradermally in a volume of 50 μl into the rostral part of skin on the back of male Balb-C mice. Both systemic or intrathecal administration of PF-3845, JZL184 or JZL195 produced similar dose-dependent antipruritic effects. Our results suggest that endocannabinoid-degrading enzymes FAAH and MAGL are involved in pruritic process at spinal level. FAAH, MAGL or dual FAAH/MAGL inhibitors have promising antipruritic effects, at least, in part through spinal site of action.

BackgroundFor centuries, cannabinoids have been known to be effective in pain states. Itch and pain are two sensations sharing a lot in common.ObjectiveThe goal of this research was to observe whether the cannabinoid agonist WIN 55,212-2 reduces serotonin-induced scratching behaviour and whether neurotoxic destruction of descending serotonergic and noradrenergic pathways mediate the antipruritic effect of WIN 55,212-2.Material and methodsScratching behaviour was induced by intradermal injection of serotonin (50 µg/50 µl/mouse) to Balb/c mice. The neurotoxins 5,7-dihydroxytryptamine (5,7-DHT, 50 μg/mouse) and 6-hydroxydopamine (6-OHDA, 20 μg/mouse) are applied intrathecally to deplete serotonin and noradrenaline in the spinal cord. WIN 55,212-2 (1, 3, 10 mg/kg, i.p.) dose-dependently attenuated serotonin-induced scratches. Neurotoxic destruction of neither the serotonergic nor the noradrenergic systems by 5,7-DHT and 6-OHDA, respectively, had any effect on the antipruritic action of WIN 55,212-2.ConclusionOur findings indicate that cannabinoids dose-dependently reduce serotonin-induced scratching behaviour and neurotoxic destruction of descending inhibitory pathways does not mediate this antipruritic effect.

Summary Flea-induced allergic dermatitis (FIAD) is frequent in cats. Despite widespread availability of flea-control products, little is known about the speed of resolution of FIAD clinical signs after treatment of affected cats with only an effective flea adulticide. To evaluate the resolution of clinical signs and pruritus in cats suffering from FIAD, twelve cats with pre-existing flea-induced allergic dermatitis, which presented to a dermatology referral service, were enrolled in an open-label non-controlled study in which all cats were treated two times with topical indoxacarb at 4 week intervals, with no concomitant treatments and followed for 56 days. Eleven cats completed the study. Mean clinical scores (SCORing of Feline Allergic Dermatitis) were reduced by 52% at week 4 and 75% at week 8. Mean owner assessed pruritus scores were reduced by 57% at week 4 and 79% at week 8. A statistically significant improvement in pruritus was observed 14 days after the initial treatment. Mean flea counts were reduced by 100% at week 4 and week 8. Topical indoxacarb treatment applied every 4 weeks without any concomitant antipruritic therapy eliminated the flea infestation, improved the clinical signs of FIAD and reduced the owner perception of pruritus in all cats.

Pruritus is a common and often times difficult to treat symptom in many dermatologic and systemic diseases. For pruritus with an inflammatory or autoimmune origin, therapies such as topical corticosteroids and antihistamines are often initiated. However, in the case that these and additional systemic therapies are ineffective, thalidomide, an immunomodulator and neuromodulator, may be a useful alternative treatment. Considerable relief of chronic pruritus has been demonstrated with thalidomide in case reports, case series, and controlled trials. Double-blind controlled studies demonstrated thalidomide's efficacy as an antipruritic agent in patients with uremic pruritus, primary biliary cirrhosis, and prurigo nodularis. In case reports, case series, and open-label trials, thalidomide significantly reduced pruritus associated with conditions such as actinic prurigo and paraneoplastic pruritus. Because of variations in study design and evaluation of antipruritic effect, it is difficult to fully understand thalidomide's role based on the evidence described to date in the medical literature. In this review, we provide an overview of the reported findings and evaluate thalidomide's utility in managing refractory pruritus in the context of its adverse risk profile. We propose that thalidomide can be an alternative or combination antipruritic treatment for patients who do not obtain enough relief from conservative therapy.

Pine tar is the end product of pine wood carbonisation following distillation using extreme heat. An extensive literature search was conducted back to the 1950s for this review. Pine tar has been used in medicine for more than 2000 years to treat a range of skin conditions because of its soothing and antiseptic properties. Pine tar should not be confused with coal tar, which has been produced from coal for approximately a hundred years. Pine tar is thought to exert its effect by reducing DNA synthesis and mitotic activity, which promotes a return to normal keratinisation. In addition, pine tar has been shown to be antipruritic, anti‐inflammatory, antibacterial and antifungal. These properties make pine tar suitable for the topical treatment of eczema, psoriasis, seborrhoeic dermatitis and other dry, itchy, flaky or inflamed skin conditions. Topical products available over‐the‐counter in Australia today contain up to 2.3% pine tar, and come in several different formulations that can be used on the entire body, including the face. Modern day pine tar is manufactured with increased purity to eliminate toxic phenol and carcinogenic components, which have been of concern in the past. Primary irritation is uncommon. In conclusion, the long experience with topical pine tar therapy and its worldwide usage, together with the evidence presented in this review, suggests that pine tar is an effective treatment with minimal safety risk.

Angelica sinensis (AS) is one of the most popular medicinal foods used as a hematopoietic herb and also traditionally applied topically for skin disorders. However, the effectiveness of AS on atopic dermatitis (AD) has not been reported yet. This study was conducted to evaluate the antipruritic and anti-inflammatory effects of AS on regulating AD-related mediators in DNCB (2,4-dinitrochlorobenzene)-induced mice. AS was topically applied to the dorsal skin of DNCB-challenged mice for 11 days. Alteration of skin thickness was measured for assessment of histological improvement. In addition, the number of mast cells, the level of serum immunoglobulin E (IgE), the counting of scratching behavior, and the expression of substance P were evaluated. Also, the expressions of cytokines, nuclear factor κB (NF-κB), phospho-IκBα, and mitogen-activated protein kinases (MAPKs) were measured for evaluating the improvement of skin inflammation. The repeated treatment of AS significantly inhibited the skin thickness, the number of mast cells, and the level of serum IgE. Moreover, AS significantly suppressed the increased scratching behavior and the expression of substance P compared to the DNCB group. Topical application of AS also reduced the level of cytokines (IL-4, IL-6, TNF-α, and IFN-γ) as well as the expressions of NF-κB, phospho-IκBα, and phospho-MAPKs in the dorsal skin. The results of our study suggest that topical application of AS might have efficacy for modulating pruritus and inflammation in AD. Further studies are required to further characterize the mechanism of actions of AS.

Approximately 88% of cutaneous T-cell lymphoma (CTCL) patients are affected by pruritus that responds poorly to current antipruritic therapies. Interleukin (IL)-31, a Th2 cytokine, has been found to be increased in the serum of CTCL patients and to correlate with itch severity. This study investigated the role of IL-31 and its receptors (IL-31 receptor-alpha [IL-31RA] and OSMRβ) in the skin of CTCL patients with mild versus moderate/severe pruritus. Expression levels of IL-31, IL-31RA, and OSMRβ in the skin were measured using immunohistochemistry and correlated to pruritus severity and disease stage. In CTCL patients with moderate/severe pruritus, IL-31 was significantly elevated in the epidermis and dermal infiltrate, while IL-31RA and OSMRβ were significantly elevated only in the epidermis. Furthermore, epidermal IL-31 levels correlated to itch severity. These results show that IL-31 may play a role in CTCL pruritus by exerting indirect effects on sensory nerves though epidermal neoplastic T-cells and keratinocytes to transmit itch.

Cyclosporine A is an immunosuppressive agent that suppresses pruritus and is currently used in the treatment of patients with severe atopic dermatitis. The aim of this study was to elucidate the antipruritic mechanism of cyclosporine A using a mouse model of atopic dermatitis. Intraperitoneal injection of cyclosporine A (5 mg/kg) significantly reduced epidermal nerve density, number of scratching bouts, dermatitis scores, and transepidermal water loss, as well as decreasing the numbers of inflammatory cells in the dermis and decreasing epidermal thickness. Intraperitoneal injection of cyclosporine A dose-dependently inhibited increased itch-related receptor gene expression, such as interleukin-31 receptor A and neurokinin-1 receptor, in the dorsal root ganglion of atopic dermatitis model mice. Thus, the antipruritic efficacy of cyclosporine A may involve reduced epidermal nerve density and expression levels of itch-related receptor genes in the dorsal root ganglion, as well as improvement in acanthosis and reduction in cutaneous inflammatory cell number.

This exploratory study was designed to evaluate the safety and efficacy profile of the topical phosphodiesterase 4 inhibitor E6005 in Japanese children with mild-to-moderate atopic dermatitis. The present randomized, multicenter study included 62 patients who were treated with 0.05% E6005, 0.2% E6005 or vehicle ointment twice daily for 2 weeks. Safety and pharmacokinetics were assessed with a focus on the occurrence of adverse events and the whole blood concentrations of E6005 and its metabolite. Exploratory efficacy evaluations included assessments of lesion severity and pruritus score. The 2-week application of topical E6005 was safe and well tolerated with no cutaneous adverse events. The whole blood concentration of E6005 was quantified in only one subject receiving 0.2% E6005 treatment, while its major metabolite was undetectable. The 0.2% E6005 group showed a greater decrease in the severity score than the vehicle group (-45.94% vs -32.26%), although this difference was not statistically significant. Similarly, the treatment success rate according to the investigator's global assessment of the total application sites was higher in the 0.2% E6005 group than in the vehicle group (34.4% vs 20.0%). Moreover, the 0.2% E6005 group showed a greater decrease in the pruritus score than the vehicle group (-37.5% vs -6.7%) in a predefined subpopulation. The efficacy of 0.05% E6005 treatment was comparable to that of vehicle treatment. These results suggest that topical 0.2% E6005 treatment is safe and effective in children with atopic dermatitis, although further large confirmatory clinical trials are warranted.

Slowly depolarizing currents applied for one minute have been shown to activate C-nociceptors and provoke increasing pain in patients with neuropathy. This study examined the effect of transcutaneous slowly depolarizing currents on pruritus in patients with atopic dermatitis. C-nociceptor-specific electrical stimu­lation was applied to areas of eczema-affected and non-affected skin in 26 patients with atopic dermatitis. Single half-sine wave pulses (500 ms, 0.2–1 mA) induced itch in 9 patients in eczema-affected areas of the skin (numerical rating scale 5 ± 1), but pain in control skin (numerical rating scale 6 ± 1).Sinusoidal stimuli (4 Hz, 10 pulses, 0.025–0.4 mA) evoked itch in only 3 patients in eczema-affected areas of the skin but on delivering pulses for one minute (0.05–0.2 mA) 48% of the patients (n= 12) reported itch with numerical rating scale 4 ± 1 in areas of eczema-affected skin. The number of patients reporting itch in eczema-affected areas of the skin increased with longer stimulation (p

Background Allergic contact dermatitis (ACD) is a highly prevalent inflammatory and immune skin disease accompanied with persistent pruritus and pain. Oxymatrine (OMT) exhibits antipruritic and anti-inflammatory effects in squaric acid dibutyl ester (SADBE) induced ACD mice model, but the need for frequent administration stipulated by short half-life and low bioavailability limits clinical application. Objective To evaluate the analgesic and antipruritic effects of OMT gel (OG), OMT sustained release microgel powder (OMP) and OMT sustained release microgel cream (OMC) in SADBE induced ACD mice, with subsequent study of the mechanism and side effects (irritation) of optimal dosage form. Method On day 11, the thickness of the right cheek skin of mice was measured and mice spontaneous behaviors were recorded for 1.5 h. In the OMC experiment, hematoxylin-eosin and toluidine blue staining were performed on the cheek skin, and the irritation of OMC was tested on the back skin of rabbits. Blood analyzer was used to measure the counts of inflammatory cells in peripheral blood. The mRNA expressions of IL-1β, TNF-α, CXCR3, CXCL10, IL-6, IL-10, IL-17A and IL-31 in cheek skin, TRPA1 and TRPV1 channels in trigeminal ganglion (TG), IFN-γ in spleen and IL-17A in thymus were measured by RT-qPCR. Results OMC, OMP and OG significantly decreased wipes and scratching bouts, alleviated skin inflammation. OMC required less frequent administration and is easier to apply, while its antipruritic effect was stronger than the analgesic effect. OMC rescued the deficits in epidermal keratinization and inflammatory cell infiltration, decreased the leukocyte count in peripheral blood, had no irritation to the broken rabbit's skin. Furthermore, OMC significantly down-regulated the mRNA expression of IL-1β, TNF-α, CXCR3, CXCL10, IL-6, IL-10, IL-17A and IL-31 in cheek skin, TRPA1 and TRPV1 channels in TG, IFN-γ in thymus and IL-17A in spleen. Conclusion We have demonstrated that OMC exhibits advanced analgesic, antipruritic and anti-inflammatory effects when compared with OG and OMP in ACD mice by regulating inflammation, chemokines, immune mediators and inhibiting the mRNA expression of TRPA1 and TRPV1. OMC has no irritation to the intact and damaged skin of rabbits.

Stellera chamaejasme, also known as “Langdu”, has been traditionally used for the management of skin-related diseases such as psoriasis and skin ulcers. The aim of this study was to determine whether S. chamaejasme and its major component, luteolin 7-O-glucoside, have a preventive effect on the development of atopic dermatitis in oxazolone-treated BALB/c mice and 2,4-dinitrochlorobenzene-treated hairless mice. The epicutaneous applications of oxazolone and 2,4-dinitrochlorobenzene evoke an experimental murine atopic dermatitis-like reaction in BALB/c mouse ears and SKH-1 hairless mice. Atopic skin symptoms, including erythema (redness), pruritus (itching), exudation (weeping), excoriation (peeling), and lichenification (skin thickening), responded to treatment with S. chamaejasme aerial parts EtOH extract for 2 or 3 weeks. Histopathological examination revealed S. chamaejasme aerial parts EtOH extract significantly reduced inflammatory cell infiltration when applied to atopic dermatitis mice. In addition, luteolin 7-O-glucoside, the major active compound of the S. chamaejasme aerial parts EtOH extract, decreased serum IgE and IL-4 levels and transepidermal water loss and increased skin hydration, therefore exhibiting strong anti-atopic dermatitis activity in 2,4-dinitrochlorobenzene-induced atopic dermatitis mice. In this study, we confirmed antipruritic and antidermatitic effects of S. chamaejasme extract and its main component luteolin 7-O-glucoside in atopic dermatitis murine models. The study shows S. chamaejasme aerial parts EtOH extract and luteolin 7-O-glucoside are most likely to be potential drug candidates for atopic dermatitis treatment.

Chronic itch is one of the disturbing symptoms of inflammatory skin diseases. Kappa opioid receptor agonists are effective in suppressing scratching in mice against different pruritogens. Nalbuphine, a nonscheduled kappa opioid receptor agonist and mu opioid receptor antagonist, has been in clinical use for post-operative pain management since the 1980s and recently has been in clinical trials for chronic itch of prurigo nodularis ( https://www.trevitherapeutics.com/nalbuphine ). We studied whether nalbuphine is effective against chronic scratching induced by rostral neck application of 1-fluoro-2,4-dinitrobenzene (DNFB), an accepted mouse model of contact dermatitis to study pruritoceptive itch. Mice were treated once a week with either saline or nalbuphine 20 min before the third, fifth, seventh, and ninth sensitizations with DNFB and the number of scratching bouts was counted for 30 min. Skin samples from the neck of mice at week 4 were used to measure protein levels and mRNA expressions of chemokines and cytokines. Different sets of mice were used to study sedation and anhedonic-like behavior of nalbuphine. We found that: nalbuphine (a) antagonized scratching in a dose- and time-dependent manner without affecting locomotion, b) decreased IL-31, and increased anti-inflammatory IL-10, and c) induced more elevations in the levels of CCL2, CCL3, CCL12, CXCL1, CXCL2, CXCL9, CXCL10, IL-1β, IL-16, TIMP-1, M-CSF, TREM-1 and M1-type macrophages compared to saline. Increases in chemokines and cytokines and M1 macrophages by nalbuphine suggest an inflammatory phase of healing in damaged skin due to scratching. Our data indicate that nalbuphine is an effective antipruritic in murine model of pruritoceptive itch.

Sophorae Flavescentis Radix (SFR) is a medicinal herb with many functions that are involved in anti-inflammation, antinociception, and anticancer. SFR is also used to treat a variety of itching diseases. Matrine (MT) is one of the main constituents in SFR and also has the effect of relieving itching, but the antipruritic mechanism is still unclear. Here, we investigated the effect of MT on anti-pruritus. In acute and chronic itch models, MT significantly inhibited the scratching behavior not only in acute itching induced by histamine (His), chloroquine (CQ) and compound 48/80 with a dose-depended manner, but also in the chronic pruritus models of atopic dermatitis (AD) and acetone-ether-water (AEW) in mice. Furthermore, MT could be detected in the blood after intraperitoneal injection (i.p.) and subcutaneous injection (s.c.). Finally, electrophysiological and calcium imaging results showed that MT inhibited the excitatory synaptic transmission from dorsal root ganglion (DRG) to the dorsal horn of the spinal cord by suppressing the presynaptic N-type calcium channel. Taken together, we believe that MT is a novel drug candidate in treating pruritus diseases, especially for histamine-independent and chronic pruritus, which might be attributed to inhibition of the presynaptic N-type calcium channel.

BACKGROUND There is a lack of controlled studies evaluating the efficacy of topical nonsteroidal agents for the treatment of canine atopic dermatitis (cAD). HYPOTHESIS/OBJECTIVES To compare the clinical efficacy of a commercial foam product (mousse), previously demonstrated to be effective in cAD (Foam A) with a foam/mousse containing components from plant extracts (Foam B). ANIMALS Eight client-owned dogs with nonseasonal mild/moderate cAD. METHODS AND MATERIALS Dogs were treated twice weekly with either Foam A or Foam B for 14 days and after a wash-out period of 14 days received the other foam in a randomized blinded study. Criteria evaluated included skin lesions [Canine Atopic Dermatitis Lesion Index (CADLI)], pruritus Visual Analog Scale (pVAS)], cosmetic evaluation and overall global product assessment by the owner and the investigator. RESULTS A significant improvement was noted for both treatment groups for both CADLI and pVAS scores (37.5% and 26.09%, respectively, for Foam A; 41.9% and 32.6%, respectively, for Foam B) (P

Background Tinea is an infectious disease by dermatophytes, of which Trichophyton species accounts for the overwhelming majority of case. Tinea often causes itching with inflammation. In terms of pruritus by fungal infection, however, tinea has not been investigated sufficiently to date. Aim To evaluate itch caused by Trichophyton infection and the effect of antifungal agents on the infection, by measuring scratch behaviour and profiles of inflammatory cytokines and chemokines. Methods We used a previously established mouse model of contact hypersensitivity induced by trichophytin, a crude extract from Trichophyton mentagrophytes. Scratching behaviour was recorded using a counting device that measured an electric current induced in a coil by movement of magnets that had been inserted into the hind paws of each animal. We investigated expression of various genes in lesional skin of mice and in normal human epidermal keratinocytes. We also investigated the antipruritic effects of the corticosteroid dexamethasone (DEX) and three antifungal agents: ketoconazole (KCZ), terbinafine (TBF) and liranaftate (LNF). Results Biphasic peaks of scratching were observed at 1 h and at 6-7 h during an observation period of 14 h after trichophytin induction. For lesional skin, RNA was extracted 24 h after trichophytin challenge, and increased expression was seen in the genes for interleukin (IL)-17A, interferon-γ, tumour necrosis factor (TNF)-α, macrophage inflammatory protein (MIP)-2 and Dectin-1, whereas there was no obvious change in the genes for IL-31 and prostaglandin (PG)E2. Furthermore, KCZ inhibited histidine decarboxylase (HDC) expression in vitro and in vivo, and inhibited scratching in the very early phase. LNF inhibited expression of thymic stromal lymphopoietin (TSLP) and IL-8 in vitro, and TSLP, TNF-α, IL-1α and MIP2 in vivo, and also scratching in the early phase. TBF did not induce any significant alterations in either gene expression or scratching. DEX suppressed expression of all the chemical mediators except HDC in vitro and in vivo, and inhibited scratching. Conclusion Antifungals can inhibit itching induced by fungal infection through different mechanisms.

Coumarin osthole is a dominant bioactive ingredient of the natural Cnidium monnieri plant commonly used for traditional Chinese herbal medicines for therapies and treatments including antipruritus and antidermatitis. However, the molecular mechanism underlying the action of osthole remains unclear. In this study, we report that osthole exerts an antipruritic effect through selective inhibition of Ca2+-permeable and thermosensitive transient receptor potential vanilloid 3 (TRPV3) cation channels that are primarily expressed in the keratinocytes of the skin. Coumarin osthole was identified as an inhibitor of TRPV3 channels transiently expressed in HEK293 cells in a calcium fluorescent assay. Inhibition of the TRPV3 current by osthole and its selectivity were further confirmed by whole-cell patch clamp recordings of TRPV3-expressing HEK293 cells and mouse primary cultured keratinocytes. Behavioral evaluation demonstrated that inhibition of TRPV3 by osthole or silencing by knockout of the TRPV3 gene significantly reduced the scratching induced by either acetone-ether-water or histamine in localized rostral neck skin in mice. Taken together, our findings provide a molecular basis for use of natural coumarin osthole from the C. monnieri plant in antipruritic or skin care therapy, thus establishing a significant role of the TRPV3 channel in chronic itch signaling or acute histamine-dependent itch sensation.

Objective: Obtain Randia Monantha Benth extract, use it as the main component in the formulation of an ointment with antipruritic characteristics. Investigate and analyze its effect through microbiological, activity, validation, and sensory assays.Methods: Soxhlet process with different solvents was performed to obtain the extract.Results: Comparing the different solvents (petroleum ether, acetone and ethanol). It was determined that the best solvent for extraction is 20% ethanol. After the different experiments, the ointment made of Randia Monantha Benth presented no contamination through the microbiological assay. Using statistical technique ANOVA along with the activity tests it was proved that the application of the ointment can reduce the pruritic effect.Conclusion: The use of Randia Monantha Benth extract as part of a formulation was possible, antipruritic effects were successful and the results obtained suggest a favorable potential for future tests and research.

is missing (Short communication)

Submitted by MARIELE GOBO DE OLIVEIRA null (mari_gobo@hotmail.com) on 2018-01-19T17:43:42Z No. of bitstreams: 1 Tese final - Mariele Gobo de Oliveira.pdf: 1534499 bytes, checksum: 18077ddad8423c32da0d78b72f1bb283 (MD5) Approved for entry into archive by ROSANGELA APARECIDA LOBO null (rosangelalobo@btu.unesp.br) on 2018-01-23T16:33:32Z (GMT) No. of bitstreams: 1 oliveira_mg_dr_bot_par.pdf: 702673 bytes, checksum: c00e5e347de838b43f505d7930182402 (MD5) Made available in DSpace on 2018-01-23T16:33:32Z (GMT). No. of bitstreams: 1 oliveira_mg_dr_bot_par.pdf: 702673 bytes, checksum: c00e5e347de838b43f505d7930182402 (MD5) Previous issue date: 2017-12-04 Outra O prurido urêmico é uma complicação frequente em pacientes renais crônicos, com impacto na qualidade de vida. Sua etiopatogênese é multifatorial e as evidências para o tratamento com emolientes, anti-histamínicos orais e drogas de ação no sistema nervoso central, como a gabapentina, são limitadas. Objetivos: 1- verificar a prevalência de prurido urêmico e seus fatores associados; 2- avaliar a eficácia na redução do prurido urêmico com a terapia tópica com cold cream após 15 dias e 3-comparar a eficácia e segurança da gabapentina versus dexclorfeniramina na redução do prurido urêmico em um período de 21 dias. Métodos: A pesquisa foi realizada entre abril de 2014 a fevereiro de 2016. Inicialmente para atender ao objetivo 1, foi realizado estudo transversal e prospectivo com pacientes em hemodiálise (etapa 1). Os dados foram obtidos por meio de prontuário eletrônico e pela aplicação de questionário estruturado. Os pacientes que relataram prurido foram convidados a participar da etapa 2 para atender ao objetivo 2, sendo este uma série de casos com seguimento longitudinal não-comparativo, no qual os pacientes receberam cold cream para uso por 15 dias. Foram avaliados a intensidade do prurido através da Escala Visual Analógica (EVA), qualidade de vida (DLQI), número de topografias corporais afetadas, período do prurido e relatório de efeitos adversos. Ao final desta fase, para atingir o objetivo 3, os pacientes (60) que ainda se queixavam de prurido de qualquer intensidade iniciaram a etapa 3, onde foram randomizados, para receber gabapentina 300 mg 3 vezes por semana (grupo GABA) ou dexclorfeniramina 6mg a cada 12 horas (grupo DEX) por 21 dias em ensaio clínico randomizado, controlado, duplo-cego, paralelo. O desfecho primário foi a diminuição do escore do prurido estimado por EVA e melhora do DLQI após os tratamentos. A análise dos dados foi realizada no software IBM SPSS 22.0, sendo considerado significativo valor de p0,7): EVA (T15-T36) reduziu mediana (p25-p75) de 5 (4-8) para 2 (0-3) no grupo GABA e de 5 (3-7) para 1 (0-2) no grupo DEX. O DLQI reduziu mediana (p25-p75) de 2 (1-3) para 1 (0-1) no grupo GABA, e de 2 (1-4) para 0 (0-1), no grupo DEX. Dezenove pacientes (32%) relataram efeitos colaterais leves/moderados, sem diferença entre os grupos, sendo sonolência o mais comum. Conclusões: Prurido urêmico tem alta prevalência em pacientes hemodialíticos e nossos dados sugerem que quanto maior o valor de creatinina e o menor valor de hemoglobina, maiores os riscos para o seu desenvolvimento. Dislipidemia, obesidade, níveis mais altos de proteína C-reativa, foram associados com maior intensidade de prurido, assim como o uso de dialisadores de alto fluxo se relacionaram com menor intensidade do prurido. O prurido urêmico foi reduzido com uso tópico de cold cream e, adicionalmente, com gabapentina ou dexclorfeniramina, com boa segurança, sem diferença entre os tratamentos. Uremic pruritus is a frequent complication in chronic renal patients, with an impact on quality of life. Its etiopathogenesis is multifactorial and as evidence for treatment with emollients, oral antihistamines and drugs with central nervous system action such as gabapentin are limited. Objectives: 1- to verify the prevalence of UP and its associated factors; 2- evaluate the effectiveness in reduction of uremic pruritus with topical therapy with cold cream after 15 days and 3- evaluate the efficacy and safety of gabapentin vs. dexchlorpheniramine in reducing the uremic pruritus after 21 days. Methods: The study was carried out between April 2014 and February 2016. Initially to reach objective 1, a cross-sectional and prospective study was performed with patients undergoing hemodialysis (stage 1). The data were obtained by electronic medical record and by the application of a structured questionnaire. Patients who reported pruritus were invited to participate in stage 2 to reach objective 2, a series of cases with non-comparative longitudinal follow-up, in which the patients received cold cream for apply for 15 days. The intensity of pruritus was evaluated by the Visual Analogue Scale (VAS), and also the quality of life questionnaire (DLQI), number of affected topographies, pruritus period and adverse effects were assessed. At the end of this phase, to reach the objective 3, patients (60) with any intensity of pruritus were included in stage 3, where they were randomized to receive gabapentin 300 mg three times per week (GABA group) or dexchlorpheniramine 6mg every 12 hours (DEX group) for 21 days in a randomized, controlled, double-blind, parallel trial. The primary end point was the decrease in VAS pruritus score and improvement of DLQI after treatments. The statistical analysis was carried out using multivariate regression models, and statistical significance was set at p 0.7). The median VAS (T15-T36) reduced (p25-p75) from 5 (4-8) to 2 (0-3) in the GABA group and from 5 (3-7) to 1 (0-2) in the DEX group. The median of DLQI reduced (p25-p75) from 2 (1-3) to 1 (0-1) in the GABA group, and from 2 (1-4) to 0 (0-1) in the DEX group. Nineteen patients (32%) reported mild/moderate side effects, with no difference between groups, with sleepiness being the most common. Conclusion: Uremic pruritus has a high prevalence in hemodialysis patients, and the data suggest that the higher the creatinine and the lower the hemoglobin levels are, the greater the risk of developing pruritus is. Dyslipidemia, obesity, and higher levels of C-reactive protein were associated with a greater intensity of pruritus, whereas the use of a high-flux dialyzer was associated with lower pruritus intensity. Uremic pruritus was reduced with topical use of cold cream and, additionally, with gabapentin or dexchlorpheniramine, with safety and no difference between them. Funadersp s/nº

Pruritus, or itch, is a frequent complaint amongst patients with cholestatic hepatobiliary disease and is difficult to manage, with many patients refractory to currently available antipruritic treatments. In this study, we examined whether manual acupuncture (MA) at particular acupoints represses deoxycholic acid (DCA)-induced scratching behavior and microglial activation and compared these effects with those induced by another pruritogen, 5'-guanidinonaltrindole (GNTI, a kappa opioid receptor antagonist). MA at Hegu (LI4) and Quchi (LI11) acupoints significantly attenuated DCA- and GNTI-induced scratching, whereas no such effects were observed at the bilateral Zusanli acupoints (ST36). Interestingly, GNTI-induced scratching was reduced similarly by both MA and electroacupuncture (EA) at the LI4 and LI11 acupoints. MA at non-acupoints did not affect scratching behavior. Intraperitoneal injection of minocycline (a microglial inhibitor) reduced GNTI- and DCA-induced scratching behavior. In Western blot analysis, subcutaneous DCA injection to the back of the neck increased spinal cord expression of ionized calcium-binding adapter molecule 1 (Iba1) and tumor necrosis factor-alpha (TNF-α) as compared with saline injection, while MA at LI4 and LI11 reduced these DCA-induced changes. Immunofluorescence confocal microcopy revealed that DCA-induced Iba1-positive cells with thicker processes emanated from the enlarged cell bodies, while this effect was attenuated by pretreatment with MA. It is concluded that microglia and TNF-α play important roles in the itching sensation and MA reduces DCA-induced scratching behavior by alleviating spinal microglial activation. MA may be an effective treatment for cholestatic pruritus.

Emollients are the mainstay of treatment for dry and sensitive skin in atopic dermatitis and other allergic dermatoses. Occlusive and moisturizing preparations (such as glycerol, propylene glycol, sorbitol, hyaluronic acid, α-hydroxy acids, unsaturated fatty acids and urea) restore the impaired barrier function of the skin, they maintain the proper pH and prevent transdermal water loss. Complementing the lipid layer of the epidermis, emollients soothe inflammation, reduce itching and have antibacterial function. Dry and sensitive skin can easily occur particularly due to the development of allergic reactions, and therefore moisturisers, should be free of preservatives, dyes and fragrances. Such products, safe, and having special characteristics for supportive treatment of various pathological conditions of the skin, are called dermocosmetics. Their essential ingredients include, among others, tannins, flavonoids, saponins and phytosterols. One of the ingredients that has the properties as antipruritics, anti-inflammatory and accelerate wound healing is an extract of the young shoots of oats Rhealba, which have been used in the treatment of patients with atopic dermatitis (AD).

Background and objective Psoriasis is one of the most common chronic inflammatory skin diseases, found in about 1–3% of the general population. Pruritus affects about 60–90% of patients with psoriasis. The aim of this review was to summarize current knowledge about the pathogenesis and treatment of this symptom in psoriasis patients. Results Majority of psoriatic patients consider pruritus as the most bothersome symptom. The pathogenesis of pruritus is still unknown but the major concept of its origin is focused on neurogenic inflammation. Possible itch mediators include neuropeptides released from dermal nerve endings upon various stimuli, which were found to be abnormally expressed in itchy psoriatic plaques. Another important phenomenon supporting the idea of neurogenic inflammation as a key player in pruritus accompanying psoriasis is abnormal innervations of psoriatic skin. Possibly increased innervation density in psoriasis may decrease the threshold for pruritic stimuli. It is also suggested that pruritus in psoriasis might be related to abnormal functioning of the peripheral opioid system. Despite the high frequency of pruritus in psoriasis, to date there is no single antipruritic therapy dedicated specifically to treat itch in this disease. Conclusions Neurogenic inflammation seems to be important for itchiness in psoriasis. Treatment of pruritus in patients with psoriasis should be directed towards the resolution of skin lesions, as disease remission usually is linked with pruritus relief.

Preclinical Research The mechanisms mediating canine pruritus are poorly understood with few models due to limited methods for inducing pruritus in dogs. Chloroquine (CQ) is a widely used antimalarial drug that causes pruritus in humans and mice. We have developed a canine model of pruritus where CQ reliably induced pruritus in all dogs tested following intravenous administration. This model is presently being used to test antipruritic activity of drug candidate molecules. This publication has been validated in a blinded cross-over study in eight beagle dogs using the reference standards, oclacitinib and prednisolone, and has been used to test a new compound, norketotifen. All compounds reduced CQ-induced pruritus in the dog. The sensitivity of the model was demonstrated using norketotifen, which at three dose levels, dose-dependently, inhibited scratching events compared with placebo.

The prevalence of allergic skin disorders has increased rapidly, and development of therapeutic agents to alleviate the symptoms are still needed. In this study, we orally or topically administered the Janus kinase (JAK) inhibitors, tofacitinib and oclacitinib, in a mouse model of dermatitis, and compared the efficacy to reduce the itch and inflammatory response. In vitro effects of JAK inhibitors on bone marrow-derived dendritic cells (BMDCs) were analyzed. For the allergic dermatitis model, female BALB/c mice were sensitized and challenged with toluene-2,4-diisocyanate (TDI). Each JAK inhibitor was orally or topically applied 30 minutes before and 4 hours after TDI challenge. After scratching bouts and ear thickness were measured, cytokines were determined in challenged skin and the cells of the draining lymph node were analyzed by means of flow cytometry. In vitro, both JAK inhibitors significantly inhibited cytokine production, migration, and maturation of BMDCs. Mice treated orally with JAK inhibitors showed a significant decrease in scratching behavior; however, ear thickness was not significantly reduced. In contrast, both scratching behavior and ear thickness in the topical treatment group were significantly reduced compared with the vehicle treatment group. However, cytokine production was differentially regulated by the JAK inhibitors, with some cytokines being significantly decreased and some being significantly increased. In conclusion, oral treatment with JAK inhibitors reduced itch behavior dramatically but had only little effect on the inflammatory response, whereas topical treatment improved both itch and inflammatory response. Although the JAK-inhibitory profile differs between both JAK inhibitors in vitro as well as in vivo, the effects have been comparable.

Atopic dermatitis (AD) is a chronic, inflammatory skin condition which affects millions of people worldwide. It is most commonly seen in children but may also progress into adulthood. Management of this complex disease requires a multi-pronged approach which can address the myriad of issues which underscore its development. Avoidance of triggering factors is imperative in establishing consistent control of skin irritation while daily moisturization can be very effective in skin barrier repair and maintenance. Judicious use of anti-inflammatory medications has been shown to make a significant impact on both treatment as well as prevention of disease. Unfortunately, pruritus, a key feature of AD, has proven much harder to control. Finally, awareness of the risks of colonization and infection in patients with AD should be incorporated into their surveillance and management plans. While our understanding has progressed greatly regarding this disease, further research is still needed regarding future directions for both treatment and prevention.

The 1st part of this publication presented the essential oils of Niaouli (Melaleuca quinquenervia Cav. cineolifera, Myrtaceae), Saro (Cinnamosma fragrans, Canellaceae), and Geranium (Pelargonium x asperum Bourbon type, Geraniaceae) used with equal parts of 0.5 to 30% in total in a mixture with vegetable oil to treat various dermatological pathologies. This 2nd part report the results on 104 cases, including 32% of fungal infections, 23% of allergies (atopic eczema mainly), 11% of bacterial infections, 8% of burns, 6% of viral infections, 4% of psoriasis, 4% of bedsores and various. The expected properties have been confirmed on these pathologies: antipruritic, anti-inflammatory, analgesic, healing, anti-infectious, immunoregulator. The results were deemed to be equivalent or better than those of conventional treatments compared to the duration, efficiency, and cost.

Background: Korean Red Ginsengda steamed root of Panax ginseng Meyerdhas long been used as a traditional medicine in Asian countries. Its antipruritic effect was recently found, but no molecular mechanisms were revealed. Thus, the current study focused on determining the underlying molecular mechanism of Korean Red Ginseng extract (RGE) against histamine-induced itch at the peripheral sensory neuronal level. Methods: To examine the antipruritic effect of RGE, we performed in vivo scratching behavior test in mice, as well as in vitro calcium imaging and whole-cell patch clamp experiments to elucidate underlying molecular mechanisms. Results: The results of our in vivo study confirmed that RGE indeed has an antipruritic effect on histamine-induced scratching in mice. In addition, RGE showed a significant inhibitory effect on histamine-induced responses in primary cultures of mouse dorsal root ganglia, suggesting that RGE has a direct inhibitory effect on sensory neuronal level. Results of further experiments showed that RGE inhibits histamine-induced responses on cells expressing both histamine receptor subtype 1 and TRPV1 ion channel, indicating that RGE blocks the histamine receptor type 1/TRPV1 pathway in sensory neurons, which is responsible for histamine-dependent itch sensation. Conclusion: The current study found for the first time that RGE effectively blocks histamine-induced itch in peripheral sensory neurons. We believe that the current results will provide an insight on itch transmission and will be helpful in understanding how RGE exerts its antipruritic effects.

The study was an attempt to determine the possibilities of using ovocystatin, a component of a new generation product of natural origin, in local therapy of atopic dermatitis in dogs by suppressing pruritus during illness. Chicken egg cystatin was used locally in the interdigital spaces of forelimbs of dogs used in the experiment. The degree of pruritus and clinical changes in the animals were defined using CADESI-03 scale before and after the beginning of the experiment. The results obtained proved that ovocystatin may be used as a substance suppressing pruritus in atopic dermatitis. Keywords: dogs, ovocystatin, pruritus, atopic dermatitis. Introduction Pruritus is defined as an autonomous feeling, independent of pain, which occurrence is related to the activity of specific mediators, spinal neurons, and cerebral cortex areas . The occurrence of pruritus in atopic dermatitis involves the activity C fibers, opioids, and psychogenic factors. Traditional methods of treatment include application of glicocorticosteroids. However, new therapeutic solutions are sought. Not only efficient medications are searched for but also the ones of the lowest toxicity and the weakest adverse reaction. Thus, chicken egg cystatin has been chosen as one of the substances which can be an alternative to traditional methods of treatment. Because of its natural occurrence, it is widely available and the methods of its efficient obtaining have been discussed in details (1, 8, 23). Cystatin is a natural substance, which is found, for example, in chicken egg white, being a humoral factor of non- specific defence. It is an inhibitor of cysteine proteinases, such as papain and ficin. Chicken egg white cystatin belongs to the type 2 of cystatin family together with human cystatin C and D (24). It is a protein composed of 116 amino acids, which has no carbohydrate component and has two disulfide bonds (7). This is a protein of 12.7 kDa molecular mass and its inhibitory properties of cystein proteinase activity result from the presence of three conservative domains (13). The first domain contains a conservative amino acid residue Gly 9 and the remaining ones create two loops of “hair pin” type. The loops influence the inhibitor functionality, stabilise it and bond the structure consisting of two α-helixes and five β-coils (25). The significance of three conservative domains in inhibiting bacterial cysteine proteinases activity was shown in experimental tests (24). It is a highly stable protein (no loss of activity after 30 min heating at 100°C, nor change of pH) (22). Freezing and thawing can cause a decrease in cystatin activity therefore it is stabilised in the glycerol solution of pH 7.5 (22, 8). It is a barrier for bacterial and viral cysteine peptidase (7, 25). Intercellular and extracellular control of protein decomposition is a very important function of cystatin (2). The objective of the study was to determine the effectiveness of ovocystatin use in local therapy of atopic dermatitis (AD) in dogs to suppress pruritus during illness.

Diospyros lotus has been cultivated for its edible fruits, which are considered to have medicinal importance. The aim of this study was to evaluate the antioxidant and antipruritic activities of water-soluble, methanol extract, and ethyl acetate (EA) fractions from D. lotus leaves. The EA fraction showed the lowest IC50 vale (DPPH: 5.3 μg/mL, ABTS: 53.8 μg/mL). Therefore, we further investigated anti-inflammatory and antipruritic effects of the EA fraction. TNF-α production increased by PMA plus A23187 treatment was significantly inhibited by the EA fraction in a dose-dependent manner. The EA fraction also inhibited histamine release from rat peritoneal mast cells stimulated by compound 48/80, which promotes histamine release. Furthermore, EA fraction had inhibitory effects on scratching behavior induced by compound 48/80 in Balb/c mice. These results suggest that the EA fraction from D. lotus leaves has potential as ameliorative agent against oxidative stress and pruritus-related disease.

Cooling or the application of mentholated liniments to the skin has been used to treat itch for centuries, yet remarkably little is known about how counter-stimuli such as these induce itch relief. Indeed, there is no clear consensus in the scientific literature as to whether or not cooling does in fact block the transduction of itch signals or if it is simply a placebo effect. This gap in our understanding led us to hypothesize that cooling is antipruritic and, like cooling analgesia, requires function of the cold-gated ion channel TRPM8, a receptor for menthol expressed on peripheral afferent nerve endings. Using a combination of pharmacologic, genetic, and mouse behavioral assays, we find that cooling inhibits both histaminergic and non-histaminergic itch pathways, and that inhibition of itch by cooling requires TRPM8 channels or intact and functional TRPM8-expressing afferent neurons. The cold mimetic menthol is also effective in ameliorating itch in a TRPM8-dependent manner. Moreover, we find that chronic itch can be ameliorated by cooling, demonstrating that this counter-stimulus activates a specific neural circuit that leads to broad itch relief and a potential cellular mechanism for treatment of chronic itch.

Background Atopic dermatitis (AD) requires a multimodal therapy and there is a need for effective adjunctive interventions. TRPM8 agonists are known to alleviate pruritus by inducing cooling. Objectives To evaluate the efficacy of a novel TRPM8 agonist, 1-diisopropylphosphorylheptane (Cryosim-1), in atopic dogs. Animals Nine client owned dogs with moderate to severe pedal pruritus associated with nonseasonal AD. Methods This was a prospective, randomized, double-blinded, intraindividual, placebo-controlled study. A 2% Cryosim-1 or placebo-vehicle cream was applied to each forepaw twice daily for seven days. The owner rated the pruritus manifestations once daily using a pedal Pruritus Visual Analog Scale (PVAS) and provided a Owner's Global Assessment of Treatment Efficacy (OGATE) at study end. Results After seven days, the numbers of dogs with a pedal PVAS

Pruritus is a major symptom of several dermatological diseases but has limited therapeutic options available. Animal models replicating the pathophysiology of pruritus are needed to support the development of new drugs. Induction of pruritus by chloroquine (CQ) in mice is widely used, although, as with similar models, it has low throughput and does not distinguish between antipruritic effects and confounding factors such as sedation. To overcome these issues, we incorporated into the model an automated system that measures both scratching and locomotor behaviour simultaneously. We combined this system with the determination of CQ levels in different tissues to understand the impact of the route of CQ administration on the pruritogenic response. We concluded that whereas oral CQ does not induce pruritus due to insufficient skin levels, the bell-shaped curve of pruritus observed following subcutaneous administration is due to toxicity at high doses. We validated the model with several drugs currently used in humans: nalfurafine, aprepitant, cyproheptadine and amitriptyline. By comparing the effects of the drugs on both scratching and locomotor activity, we concluded that nalfurafine and aprepitant can exhibit efficacy at doses devoid of central effects, whereas central effects drove the efficacy of the other two drugs. This was further confirmed using non-brain-penetrant drugs. Moreover, as anticipated, anti-inflammatory drugs showed no efficacy. In conclusion, the use of an automated integrated behavioural assessment in CQ-induced pruritus makes the assay suitable for screening purposes and allows for a correct interpretation of the antipruritic effect of the compounds evaluated.

Background It has been reported that topical hypochlorous acid (HOCl) formulations lead to relief of itch in human patients with atopic dermatitis, however the specific anti-pruritic mechanism of action remains unclear. Objective To confirm itch relief and reduction of lesions in a mouse model of atopic dermatitis and to elucidate possible HOCl's mode of action. Methods In this study, the effects of topical administration of HOCl hydrogel (0.05%) on atopic dermatitis-like lesions in NC/Nga mice model as well as in vitro effects of HOCl on dorsal root ganglia neurons and mouse bone marrow derived dendritic cells (mBMDC) were investigated. NC/Nga mice were sensitized with house dust mite allergen and treated topically with HOCl hydrogel both preventively as well as therapeutically against established lesions. Allergen challenge was continued during HOCl hydrogel application. Results Treatment with HOCl hydrogel prevented the development of lesions and scratching bouts during the whole observation period. When administered after full development of lesions, HOCl reduced lesions and scratching behaviour to a similar extent as a positive control 0.1% betamethasone dipropionate ointment. The reduced inflammatory response by HOCl treatment was demonstrated by reduced secretion of inflammatory cytokines in affected skin tissue from NC/Nga mice. In addition, HOCl significantly reduced IL-12 production in mBMDC. The diminished scratching behaviour was confirmed by impaired response to several pruritogens in dorsal root ganglia neurons excised from NC/Nga mice after termination of the studies. The response to the stimuli was also reduced by pre-incubation of sensory neurons from untreated BALB/c mice with 0.0001% HOCl. Conclusions and Clinical Relevance These data indicate a direct reduction of sensory response by HOCl, leading to significantly reduced itch and inflammation in vivo. This article is protected by copyright. All rights reserved.

Background Botulinum neurotoxin (BTX) A possesses various biological activities, including anti-inflammatory and antipruritic actions. Human and animal studies have shown that BTX is effective in treating histamine-induced itch, lichen simplex chronicus, psoriasis, rosacea, allergic rhinitis, and scar prevention. However, its effect on atopic dermatitis (AD) has not been studied yet. Objective To examine the effect of BTX on AD using a mouse model. The primary outcome was skin thickness and transepidermal water loss (TEWL), and the secondary outcome was the alteration in skin severity scores, histological, and laboratory test results. Methods Forty-two NC/Nga mice (a mouse model for AD) were allocated into 6 groups (the untreated, 2-Chloro-1,3,5-trinitrobenzene [TNCB] alone, TNCB + BTX 30 U/kg, TNCB + BTX 60 U/kg, TNCB + vehicle [0.9% saline], TNCB + 0.03% tacrolimus). Those of the BTX group received intradermal injections of BTX on the rostral back once on the day of TNCB sensitization. The effect of BTX in TNCB-treated NC/Nga mice was assessed by measuring skin thickness, TEWL (primary outcome), the skin severity scores, histological changes of test skin including mast cell count, interleukin (IL)-4 mRNA and protein expression, and total serum IgE (secondary outcome). Results A single intradermal injection of BTX significantly suppressed skin thickness and TEWL in the TNCB-applied skin. The clinical severity scores, acanthosis and mast cell infiltration, were less in the BTX groups. BTX injection also inhibited TNCB-induced increase in IL-4 mRNA and protein expression in mice, but its effect on serum IgE level was not significant. Conclusion The preliminary results suggest that BTX may be a novel approach to the prevention and supplemental treatment of acute AD lesions.

Objective: Vanillosmopsis arborea Baker (Asteraceae) has high economic value from Chapada to Araripe and its bark essential oil is a potential source of alpha-bisabolol. The present study aimed to elucidate the antinociceptive and antipruritic properties of the essential oil of V. arborea Baker (EOVA) in mice. Materials and Methods: The antinociceptive activity was assessed using the capsaicin, glutamate, hot plate and cold allodynia tests. The antipuritic effects were also verified based on histamine-induced scratching behavior. Results: EOVA reduced the paw licking induced by capsaicin, but not that induced by glutamate. The essential oil increased the latency time in the hot plate, attenuated the cold allodynia induced by acetone and inhibited histamine-induced scratching behavior. Conclusion: The experimental data demonstrated that EOVA showed central and peripheral antinociceptive activity and antipruritic effect.

SummaryBackground and Aims Pruritus frequently reduces quality of life (QOL) in patients with senile xerosis. This study investigated the moisturizing and antipruritic effects of a topical emollient containing a diethylene glycol/dilinoleic acid copolymer (D/DC) in patients with pruritic senile xerosis. Methods This single-blind study involved 50 subjects, aged 50-75 years. Patients were randomized to self-applied treatment of the lower legs with 10% (n = 20) or 20% (n = 20) D/DC-containing cream, white petrolatum (n = 5), or no treatment (n = 5) thrice daily for four weeks. Clinical scores of skin dryness and scratch marks, skin conductance, and Skindex-16 were evaluated before and after treatment. The degree of pruritus was evaluated by visual analog scale (VAS) score once a week. Results Patients treated with 10% and 20% D/DC showed significant improvements in skin dryness and scratch mark scores, as well as increased skin conductance, compared with the untreated group, whereas white petrolatum treatment improved only skin dryness scores. Moreover, patients treated with 20% D/DC showed significant improvements in skin dryness scores and skin conductance compared with white petrolatum treatment. The VAS scores in the D/DC-treated and white petrolatum-treated groups were significantly lower than in the untreated group, being particularly lower after one week of treatment with 20% D/DC. Conclusion Topical application of an emollient containing D/DC is effective in improving skin dryness and pruritus in patients with senile xerosis.

BACKGROUND: Chronic itch is difficult to treat and associated with significantly decreased life quality. Topical low-concentration capsaicin (0.006-0.05%) has previously been investigated and applied in therapy of itch but contradictory evidence exits regarding its efficacy.OBJECTIVES: This placebo-controlled, double-blinded study investigated the effect of 8% topical capsaicin applied for 1 and 24 hours on evoked itch, neurogenic inflammation and itch-associated dysesthesia.METHODS: Sixteen healthy volunteers (22±0.5 years, 9F) were treated with capsaicin for 1h and 24hrs, and vehicle for 24hrs on each volar forearm. After capsaicin/vehicle application, histamine (1%, administered prick test lancets) and cowhage (40-45 spicules) were applied in pretreated areas. Evoked itch and pain intensities were recorded for 10 minutes using a visual analog scale (0-10 cm), while Sensitivity To Touch-evoked Itch (STTI) was evaluated using von Frey filaments before/after itch provocations (as a measure of punctuate hyperknesis). Neurogenic inflammation was assessed using perfusion-imaging.RESULTS: In the vehicle-pretreated areas peak itch responses to histamine and cowhage were 4.67±0.58 and 5.15±0.71, respectively. Capsaicin-pretreatment reduced peak itch responses to both histamine and cowhage, after 24-hour pretreatment to 1.41±0.58 (p=0.003) and 0.81±0.18, (pCONCLUSIONS: Twenty-four hours of topical 8% capsaicin-pretreatment reduced histaminergic and non-histaminergic itch by ≈75%, while only significant reduction was achieved for non-histaminergic itch in a standard 1-hour treatment. Further investigations are needed to elucidate the clinical potential of high-concentration capsaicin as an antipruritic. This article is protected by copyright. All rights reserved.

A frequent empirical observation is that cold-induced counter-irritation may attenuate itch. The aim of this randomized, single-blinded, exploratory study was to evaluate the counter-irritation effects of cold-stimulation and topical application of transient receptor potential TRPA1/M8-agonists (trans-cinnamaldehyde/L-menthol, respectively), on histamine-induced itch, wheal and neurogenic inflammation in 13 healthy volunteers. Histamine 1% was applied to the volar forearms using skin prick-testing lancets. Recorded outcome-parameters were itch intensity, wheal reactions and neurogenic inflammation (measured by laser-speckle perfusion-imaging). Homotopic thermal counter-irritation was performed with 6 temperatures, ranging from 4°C to 37°C, using a 3 × 3-cm thermal stimulator. Chemical "cold-like" counter-irritation was conducted with 40% L-menthol and 10% trans-cinnamaldehyde, while 5% doxepin was used as a positive antipruritic control/comparator. Cold counter-irritation stimuli from 4°C to 22°C inhibited itch in a stimulus-intensity-dependent manner (p