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Atopic dermatitis (AD) and psoriasis are common skin diseases with a high negative impact on patients' quality of life. Both diseases are mediated by a pro-inflammatory infiltrate consisting of several cell types, such as T-cells, antigen-presenting cells and granulocytes and display disturbed keratinocyte differentiation. Given the fact that histamine levels are also highly elevated in inflamed skin, it is likely that histamine plays a relevant role in disease pathology. However, antagonists blocking histamine H1 receptor or H2 receptors are largely ineffective in reducing chronic symptoms in AD and psoriasis. Over the last years, much research has been undertaken to shed light into the mode of action of the most recently discovered histamine H4 receptor. This research has shown that H4 receptor antagonists display antipruritic and anti-inflammatory effects not only in mouse models but also in first human clinical trials, and therefore, H4 receptors might present a novel therapeutic target. In this review, we summarize the effects of the H4 receptors on different cell types, mouse models and clinical studies in regard to AD and psoriasis respectively. LINKED ARTICLES: This article is part of a themed section on New Uses for 21st Century. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.3/issuetoc.

The Janus kinase 1/3 inhibitor tofacitinib has demonstrated an antipruritic effect in two phase III studies in psoriasis. However, the mechanisms behind this antipruritic effect are still unknown. We presently investigated whether tofacitinib affects spontaneous itch as well as expression of itch-related cytokines and epidermal nerve fiber density (ENFD) in the imiquimod-induced mouse model of psoriasis. Psoriasis-like skin lesions were produced by daily topical application of imiquimod to the back skin. Imiquimod treatment resulted in spontaneous scratching, which was significantly inhibited by tofacitinib treatment. Imiquimod treatment significantly increased mRNA expression of Il22, Il23, and Il31, reduced peptidergic ENFD, and increased nonpeptidergic ENFD compared to naive mice. Tofacitinib significantly decreased the expression of those cytokines and increased peptidergic ENFD without a significant effect on nonpeptidergic ENFD. Tofacitinib may inhibit psoriatic itch through inhibition of cytokine expression as well as modulation of epidermal innervation.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease, characterized by intense itch, typical localization and a specific image of skin lesions. Pathogenesis of pruritus in AD is not fully understood, but recent studies emphasize the role of interleukin-31 (IL-31). This relatively recently described cytokine is considered to be a potential mediator inducing pruritus in AD. Aim of the Work: was to assess the correlation of serum IL-31 level and the disease severity in children with AD. Patients and Methods: a case control study. Sera were obtained from 50 AD children and 30 healthy volunteers. IL-31 levels were measured using ELISA with standard kits from EIAab R&D Systems. Serum IL-31 levels were correlated with AD disease activity. Disease severity in children with AD was assessed using the SCORAD (Severity scoringof atopic dermatitis) index. Results: Serum IL-31 level was significantly higher in AD children (Mean ± SD 99.73 ± 75.93) than in healthy children (Mean ± SD 54.01 ± 57.36), (p-value = 0.019). Serum IL-31 levels correlated positively with the calculated severity score (SCORAD index), (rs = 0.480, p- value

Background Pruritus reduces quality of life and may occur at different sites of the body. To alleviate pruritus, lipid replenishing and rehydration of the skin is often unsatisfactory. Thus, products with additional antipruritic effects are needed. Objectives Antipruritic effects and cosmetic properties of two different emulsions, water-in-oil (w/o) or oil-in-water (o/w), and a shampoo containing a lipophilic Echinacea purpurea root extract (Ec.-extract) were assessed in adults suffering from pruritus. Methods Adults (n = 55) with pruritus of the body applied a w/o emulsion for 2 weeks. In a separate study, adults (n = 33) with a pruritic scalp applied an o/w-emulsion for 4 weeks. In a third study, shampoo (n = 34) was applied for 4 weeks. Objective (erythema, dryness, and papules) and subjective (intensity, duration, and burden of pruritus) parameters were assessed. Results Treatment with the w/o emulsion significantly reduced erythema and dryness (P < 0.0001) as well as pruritus (in 93% of participants) on the body. Treatment with the o/w-emulsion on the scalp significantly (P < 0.0001) reduced objective (erythema in 61% and dryness in 85% of participants) and subjective (85% of participants had reduced pruritus) parameters. Similar results in reduction of dryness (76% of participants) and pruritus (70 % of participants) were seen after 4 weeks of shampoo use. Conclusion Independent from the type of emulsion (w/o or o/w), cosmetic products containing a proprietary Ec.-extract significantly reduced objective and subjective parameters in adults suffering from acute or chronic pruritus exhibiting excellent tolerability.

Background: Scabies, an infectious disease caused by Sarcoptes scabiei mites, is still one of the most common skin diseases found in developing countries, including Indonesia. The 5% permethrin cream for scabies treatment has been investigated as having 2–3 time to cure scabies. Tea Tree Oil (TTO) is one of the agents that has been proven to have acaricidal potential as an anti-inflammatory, antibacterial, and antipruritic agent. It has minimal side effects in topical use. Purpose: To evaluate the effectiveness of 5% TTO cream and 10% TTO cream in scabies treatment of pediatric patients. Methods: This was an experimental, analytical study with controlled clinical trial methods, and a double-blind, parallel design comparing 5% TTO cream (treatment 1), 10% TTO cream (treatment 2), with 5% permethrin cream (control) to children with scabies. Result: The 5% TTO cream gave a cure rate of 61.5% and was significantly different from the 5% permethrin cream groups with a p-value = 0.044 in the first week of the study. The 5% permethrin cream gave a cure rate of 15.4%, and the cure rate of 10% TTO cream was 53.8% in the first week of the study. Conclusion: There was a significant difference between the 5% TTO cream and 5% permethrin cream in the first week of the study. The highest and fastest cure rates were found in the 5% TTO cream treatment group.

Ruxolitinib (RUX) cream demonstrated potent anti-inflammatory and antipruritic efficacy in a phase 2 study in adults with atopic dermatitis (AD).To evaluate 8-week efficacy and safety in 2 phase 3 studies of RUX cream in patients with AD.Topical Ruxolitinib Evaluation in Atopic Dermatitis Study 1 (NCT03745638) and Study 2 (NCT03745651) enrolled patients aged ≥12 years with AD for ≥2 years, an Investigator's Global Assessment score of 2/3, and 3%-20% affected body surface area. Patients were randomized 2:2:1 to twice-daily 0.75% RUX cream, 1.5% RUX cream, or vehicle cream for 8 continuous weeks. The primary endpoint was Investigator's Global Assessment treatment success at week 8 (Investigator's Global Assessment score of 0/1 and ≥2-grade improvement from baseline).In the Topical Ruxolitinib Evaluation in Atopic Dermatitis Study 1 and 2, 631 and 618 patients were randomized (631/577 analyzed for efficacy). Significantly more patients achieved Investigator's Global Assessment treatment success with 0.75% RUX cream (50.0%/39.0%) and 1.5% RUX cream (53.8%/51.3%) versus vehicle (15.1%/7.6%; P .0001) at week 8. Significant itch reductions versus vehicle were reported within 12 hours of first application of 1.5% RUX (P .05). Application site reactions were infrequent (1%) and lower with RUX versus vehicle; none were clinically significant.Longer-term safety data are not yet available.RUX cream showed anti-inflammatory and prompt antipruritic effects with superior efficacy versus vehicle and was well tolerated.

Itch (or pruritus) was not previously recognized as a serious symptom of psoriasis. However, approximately 60–90% of psoriatic patients with pruritus have stated that it deteriorates their quality of life. Since conventional antipruritic therapies, such as antihistamines, only exert limited effects, the establishment of a treatment option for itch in psoriasis is urgently needed. Although a definitive drug is not currently available, various itch mediators are known to be involved in pruritus in psoriasis. In this review, we describe the clinical features of pruritus in psoriasis, classify a wide range of itch mediators into categories, such as the nervous, immune, endocrine, and vascular systems, and discuss the mechanisms by which these mediators induce or aggravate itch in the pathophysiology of psoriasis.

Doxepin, a tricyclic antidepressant, is the most efficacious antipruritic available to dermatologists; however its use is often suboptimal because of significant interindividual variability in doxepin plasma levels and clinical response between patients taking the same dose. As result, the Food and Drug Administration approves a maximum dose of 300 mg of doxepin per day and a 10 mg per cc liquid doxepin concentrate. These allow patients to significantly increase or decrease their dose, due to either a lack of clinical efficacy or side effects at typical dermatologic doses (often 10-25 mg per day). This review initially discusses the unique advantages of doxepin in dermatology. Then, it explores internal and external reasons why doxepin plasma levels and clinical response vary so significantly between patients, including genetic polymorphisms, drug interactions, comorbidities, sex, and ethnicity. Blood level monitoring is introduced, a tool dermatologists can use to optimize doxepin dosing in patients responding subtherapeutically to typical dermatologic doses. Without blood level monitoring, patients initially unresponsive to treatment could be labeled treatment failures when in fact they may be cases of inadequate dosing. Blood level monitoring allows for safe dose adjustments in these individuals to maximize patients' chances of achieving therapeutic success with this agent.

The maintenance of a healthy skin barrier is crucial to prevent and treat atopic dermatitis (AD) lesions and avoid infections. Glycomacropeptide (GMP) is a bioactive peptide that has demonstrated promising results as an anti-inflammatory and antipruritic therapy for experimental AD. This study aimed to analyze the effect of GMP on impaired cutaneous barrier-related signs in a rat model of AD lesions. AD-like dermatitis was induced on the skin by repeated topical applications of 2,4-dinitrochlorobenzene, and animals were orally administered GMP before or after AD induction. The expression of skin structural proteins and antimicrobial peptides (AMPs) was evaluated by immunoblot or immunohistochemistry, epidermal thickening was evaluated by histochemistry, the level of IFN-γ and changes in the microbiota were evaluated by quantitative polymerase chain reaction, and the quantity of fecal short-chain fatty acids (SCFAs) was evaluated by gas chromatography. GMP administration significantly increased filaggrin, β-defensin 2, and cathelicidin-related AMP expression in AD-like lesions. Involucrin expression was not modified. In GMP-treated animals, epidermal thickening and IFN-γ expression were strongly reduced in damaged skin. GMP treatment impacted the skin microbiota and prevented Staphylococcus aureus colonization, which is associated with AD. In addition, high levels of Bifidobacterium were detected in the feces of GMP-treated animals, and the acetic acid and butyric acid contents increased in animals prophylactically administered GMP. These results suggest that GMP markedly prevents or reverses skin barrier damage in rat AD-like lesions through a bifidogenic effect that induces fecal SCFA production with prolonged treatment. Our findings provide evidence that GMP may represent an optimum strategy for the therapy of the dysfunctional cutaneous barrier in AD.

Itch is the commonest skin-related symptom and can be influenced by visual cues as exemplified by the phenomenon of "contagious itch." Colors are visual cues able to modify somatosensory inputs. We explored the relationship of colors and itch and the impact of color viewing on itch intensity. In this cross-sectional study, patients suffering from itch with a mean intensity of ≥2 on a Numerical Rating Scale during the last 7 days were evaluated. The study consisted of a questionnaire-based part using The Manchester Color Wheel and the ItchyQoL, followed by an interventional part. All 72 itch patients were able to match their itchy sensation with a color: In 68 patients (94.4%) this "pruritic" basic color was red. Likewise, all patients were able to define a subjective "antipruritic" color: The leading basic color choice was blue (31/72, 43.0%) followed by green (21/72, 29.1%), yellow (7/72,9.7%) and others. The impairment of the itch-related quality of life (as measured by the ItchyQoL) correlated with the brightness and saturation of the pruritic and antipruritic colors. Ten patients were visually exposed to their subjective antipruritic and pruritic color during 10 minutes resulting in a significant decrease and increase of itch intensity compared to baseline (5.1 ± 1.52 vs. 2.8 ± 1.47 [0-10 Numerical Rating Scale, NRS], p=0.0004 and 4.9 ± 1.66 vs. 6.8± 2.09 NRS, p=0.0009). These results indicate that itch can be modified by color viewing and colors matter when treating itch patients. However, further investigations are required to elucidate the therapeutic potential of colors in itch patients.

Marco Ardigò,1 Chiara Franceschini,1 Elena Campione,2 Terenzio Cosio,2 Caterina Lanna,2 Luca Bianchi,2 Massimo Milani3 1Clinical Dermatology, San Gallicano Dermatological Institute, Rome, Italy; 2Dermatology Institute, Università Tor Vergata, Rome, Italy; 3Medical Department, Cantabria Labs Difa Cooper, Caronno Pertusella, VA, ItalyCorrespondence: Massimo MilaniMedical Department, Cantabria Labs Difa Cooper, Caronno Pertusella, ItalyEmail massimo.milani@difacooper.comPurpose: To investigate the efficacy of a cream containing purified omental lipids 10% and three anti-itching substances (polidocanol/stimutex/palmitoylethanolamine) in elderly subjects with chronic pruritus/prurigo nodularis (CP/CPN).Patients and Methods: Thirty-five subjects (6 men; mean age 67± 4 years) with CP/CPN were enrolled in a prospective, assessor-blinded, 4-week study. The cream was applied twice daily in the most affected body area. The primary endpoints were the evolution of the 10-cm visual analogue itch severity scale (VAS) and the 4-point verbal itching rating scale (VRS) (from 0 to 3). Secondary endpoints were the evolution of optical coherence tomography (OTC) of four skin parameters (acanthosis/hyperkeratosis/scale/dermal vascular pattern), assessed in a target lesioned area, and the transepidermal water loss (TEWL). Study endpoints were evaluated at baseline and after 2 and 4 weeks by an investigator unaware of the type of treatment.Results: All the enrolled subjects concluded the trial. At baseline, the mean±SD scores for VAS and VRS were 4.9± 2.2 and 1.7± 0.7, respectively. The treatment was associated with a significant reduction (p=0.0001) of VAS score of 60% at week 2 and of 86% at week 4. VRS score was significantly reduced by 49% after 2 weeks and by 81% after 4 weeks, in comparison with baseline. TEWL (expressed as g/m2/h) mean values were 18± 5.4 at baseline and 12.7± 4.4 at week 2 and 9.8± 4.7 at week 4 (P=0.0001 vs baseline). All the OCT parameters evaluated improved during active treatment; acanthosis grade was 0.22 mm at baseline, 0.19 mm at week 2 and 0.17 mm at week 4 (p=0.0005), representing a 23% reduction in comparison with baseline. The product was very well tolerated.Conclusion: This purified omental lipid with three anti-itching components cream reduces significantly itch intensity in subjects with chronic pruritus/prurigo nodularis, improving the skin barrier function and skin structure.Trial Number: ISRCTN869561669.Keywords: chronic pruritus, prurigo nodularis, purified omental lipids, itch, antipruritic

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by intense pruritus and skin lesions. The exact cause of AD is not yet known and the available therapeutic strategies for AD are limited. Fructus cnidii is commonly used in traditional Chinese medicine as an herb for treating chronic itch. However, the mechanism underlying the antipruritic effects of Fructus cnidii is not well understood. In the present study, we investigated the antipruritic effect of locally administered ethyl acetate extract from Fructus cnidii (EAEFC) to 2,4-dinitrofluorobenzene- (DNFB-) induced AD in a mouse model. The scratching behavior, skin thickness, dermatitis score, weight, blood immunoglobulin E (IgE) level, and itch-related cytokine levels were subsequently monitored and evaluated. Results showed that EAEFC treatment attenuated the DNFB-induced AD-like symptoms by alleviating the skin lesions and decreasing the dermatitis score. Hematoxylin and eosin (H&E) and toluidine blue (TB) staining analyses demonstrated that EAEFC mitigated the DNFB-induced increase in skin thickness and prevented the infiltration of mast cells. Behavioral tests showed that EAEFC decreased the DNFB-induced acute and chronic scratching behaviors. Furthermore, EAEFC reduced the levels of itch-related cytokines, such as thymic stromal lymphopoietin (TSLP), interleukin- (IL-) 17, IL-33, and IL-31, and the DNFB-induced boost in serum IgE. Collectively, these results suggest that EAEFC is a potential therapeutic candidate for the treatment of chronic itch in AD.

Background. One of the most important tasks in the treatment of atopic dermatitis (AD) is alleviation of racking skin dryness and persistent pruritus, because these factors exert a significant influence on worsening patients’ quality of life. Cryotherapy being a new form of rehabilitation in AD may supplement and support a long-term process of AD treatment, because it has anti-inflammatory and antipruritic effects and exerts a positive influence on the nervous system. Methods. 14 adults (mean age 32±10.8) with mild to moderate AD were enrolled. WBC (15 treatments in total) took place in winter 2018/2019. Patient skin parameters (hydration of the epidermis, sebum level, and skin pH level) were measured with probes produced by Courage + Khazaka Electronic GmbH. Results. Changes were observed in the hydration level of the epidermis. The SCORAD index evaluating the AD intensity level also changed (decreased). Conclusion. Due to these properties, hypothesis has been put forward that WBC can be an effective, supporting method in the treatment of AD.

The tree is native to south China, Taiwan, south Japan, Korea, Vietnam, Formosa and Tonkin, India, Sri Lanka, Europe, Malaya, the Philippines, Eastern and Southern Africa, Central America, and the United States. Camphor, freely soluble in water, is chiefly distilled from the root trunk and branches, and is purified by sublimation and condensed into balls, tablets or sublime powder. d-camphor is highest in bark and lowest in fruits. Externally, camphor is rubefacient, resolvent, disinfectant, antipruritic, analgesic and anesthetic; internally, it is cardiostimulant, cardiorefrigerant, antipyretic, stomach tonic, carminative and constipative. In therapeutic doses, it stimulates heart, respiration, and the vasomotor ganglia, and stimulates and increases sexual desire, after a while it depresses sexual functions. It stimulates uterus and increases menstrual flow. As an anodyne it relieves pain, moderates sexual excitement and other neurotic affections. Different chemotypes of C. camphora demonstrate anti-inflammatory effect on Freund’s adjuvant-induced arthritis in rats. Essential oil possesses significant anticandidal activity, arrests growth of toxigenic strains of A. flavus, A. niger, and is also toxic to human breast tumor cells. Daily topical application of 1/3 diluted camphor oil with glycerol, and metronidazole orally for fifteen-days to females suffering from erythema to telangiectatic rosacea, due to Demodex folliculorum infestation, produced good results without any apparent side effect. Safrole is a component of essential oil that induces hepatomas in rats in concentration of 0.5–1% of diet.

Chronic itch is a troublesome condition and often difficult to cure. Emerging evidence suggests that the periaqueductal gray-rostral ventromedial medulla (PAG-RVM) pathway may play an important role in regulation of itch, but the cellular organization and molecular mechanisms remain incompletely understood. Here, we report that a group of RVM neurons distinctively express the G protein-coupled estrogen receptor (GPER), which mediates descending inhibition of itch. We found that GPER+ neurons in RVM were activated in chronic itch conditions in rats and mice. Selective ablation or chemogenetic suppression of RVM GPER+ neurons resulted in mechanical alloknesis and increased scratching in response to pruritogens, whereas chemogenetic activation of GPER+ neurons abrogated itch responses, indicating that GPER+ neurons are antipruritic. Moreover, GPER-deficient mice and rats of either sex exhibited hypersensitivity to mechanical and chemical itch, a phenotype reversible by μ type opioid receptor (MOR) antagonism. Additionally, significant MOR phosphorylation in the RVM was detected in chronic itch models in wild-type but not in GPER-/- rats. Therefore, GPER not only identifies a population of medullary antipruritic neurons but may also determine the descending antipruritic tone through regulating μ-opioid signaling.

The therapeutic effects of synthetic tannins are based on their binding action, as well as on their anti-pruritic, antimicrobial and anti-inflammatory effects. Materials and methods. A clinical study of Neotanin spray, Neotanin lotion (suspension) and Neotanin cream was carried out in 8 clinical centres during the period from June, 2017 to January, 2018. The study had an open and non-comparative character. The study included 68 patients of both sex es aged from 1 month to 80 years suffering from eczema dermatosis in the acute weeping phase, including cases with complications after secondary infections (including eczema elements localized on the face). Before the study, information on the clinical history, demographic data, co-morbidities, physical examination data of the patients was collected. The treatment regimen included 2 stages: 1) Neotanin in the spray or lotion (suspension) form 3–4 times per day during 1–5 days, up to the full drying of eczema elements; 2) Neotanin in the cream form 3 times per day, up to the disappearance of the clinical manifestations of skin dermatosis. The duration of the study ranged from 5 to 14 days: the study was completed when a patient had achieved remission. The criteria for assessing the drug efficacy were as follows: dynamics of subjective complaints, objective assessment of the patient's condition (the presence and severity of clinical symptoms), dynamics of the Dermatology Life Quality Index (DLQI). Results. Neotanin preparations showed a high efficacy in the acute and subacute stages of the inflammatory process as an antipruritic agent. Itching stopped within 5 minutes after the drug application, with the antipruritic effect lasting for an average of 3–4 hours. In 85 % of the patients, marked excoriations were absent on the 3rd day of treatment. Neotanin demonstrated a pronounced anti-inflammatory effect. In 92 % of the patients, the symptoms of erythema and edema were significantly reduced one week after the beginning of treatment, with the manifestations of inflammatory exudation being conclusively decreased. One week following the beginning of treatment, 100 % of the patients demonstrated no oozing lesions. The absence of serious undesirable effects in the patients during the study evidences to the good tolerability and safety of this drug.

New indications are being reported for intradermal botulinum toxin type A (BTX-A) owing to its anti-inflammatory and antipruritic actions. Its successful use for dyshidrotic hand eczema and lichen simplex has been reported in a few cases, while its utility in dry palmar eczema not associated with hyperhidrosis has not yet been investigated. The aim of this study was the assessment of the additive efficacy and tolerability of BTX-A in chronic dry palmar eczema. This prospective non-randomized side-by-side comparative study included 30 cases of chronic bilateral dry palmar eczema with no associated hyperhidrosis. Combined emollients and topical mid-potency steroid on one side were compared with an additive 100 units of intradermal BTX-A on the other side for efficacy and tolerability using both patient- and physician-oriented scores over a period of 6 months. Timing and extent of improvement and relapse were recorded on both sides, together with the frequency of development of side-effects. Both lines were effective and well tolerated, with significantly greater reduction of symptom and sign scores and higher overall patient satisfaction on the side receiving BTX-A, an effect which lasted for a significantly longer duration on this side (4 months) as compared with the other side (1 month). In conclusion, intradermal BTX-A at a dose of 100 units/palm is beneficial and well tolerated in chronic dry palmar eczema. Compared with topical steroid and emollients alone, its addition yielded superior efficacy that was longer lasting and more satisfactory to the patients, while exerting a steroid-sparing effect.

Agonists of the kappa opioid receptor (KOR) have been shown to block the rewarding effects of drugs of abuse, but with negative side effects. The antipruritic drug nalfurafine, approved in Japan in 2009, is a potent, selective KOR agonist that does not cause significant side effects in humans. Nalfurafine has not been extensively tested for its effect on drug reward and reinforcement in preclinical models. The goal of this study was to compare the effects of nalfurafine and a reference KOR agonist for a variety of KOR-mediated endpoints in male C57BL6 mice. Specifically, we aimed to evaluate the “therapeutic window”—doses of agonists lower than those eliciting negative side effects, while still effective for desired therapeutic effects. In this study, several low doses of nalfurafine and U50,488 were tested for serum prolactin release, rotarod-mediated sedation, and place-conditioning in male C57BL6 mice. These agonists were also tested for effects on intravenous cocaine self-administration, both on an FR1 schedule and on a progressive ratio schedule for 0.5 mg/kg/infusion cocaine. Serum prolactin levels increased following doses of both nalfurafine (3 μg/kg and 10 μg/kg) and U50,488 (3 mg/kg). These doses did not cause sedation in the rotarod assay or aversion in a place-conditioning assay, but blocked conditioned place preference for cocaine. Immediate pretreatment of mice with 10 μg/kg nalfurafine and 3 mg/kg U50,488, however, potentiated cocaine self-administration. Further 10 μg/kg nalfurafine was also observed to potentiate cocaine-seeking behavior as demonstrated by increased progressive ratio break point. Both nalfurafine and U50,488 showed a separation of negative side effects and the modulation of cocaine reward, suggesting this effect of KOR agonists at low doses may be characteristic of the KOR system in general. At higher doses, nalfurafine had similar effects to traditional KOR agonists like U50,488, indicating that its relative potency, rather than differences in KOR signaling, may be responsible for its unique effects in humans.

Chronic pruritus, or itch lasting greater than 6 weeks, is an increasingly common and debilitating medical problem. Recent studies have unveiled previously unrecognized neuroimmune axes whereby inflammatory cytokines act directly on the nervous system to promote itch. Thus, the emergence of newer targeted biologic therapies has generated the possibility of novel treatment strategies for chronic itch disorders. This article reviews the pathophysiology of multiple chronic itch disorders, including atopic dermatitis, chronic idiopathic pruritus, chronic urticaria, and prurigo nodularis. Furthermore, new and emerging immunomodulatory therapies that will likely alter current treatment paradigms are discussed.

Lichen planus (LP) is a moderately prevalent inflammatory disorder that affects the skin and the oral mucosa, leading to a characteristic appearance and causing severe itching.To assess the potency of transcutaneous electrical nerve stimulation (TENS) as an antipruritic line of treatment in patients with LP.We enrolled 30 patients with LP who had a history of recurrent relapses of confined pruritus forcing them to scratch or rub the affected area intensively. Patients were treated with TENS three times per week for 4 weeks. Severity of itching was estimated by visual analogue scale (VAS) and Dermatology Life Quality Index (DLQI).There was a statistically significant decline in mean VAS score at weeks 2 and 4 of treatment compared with baseline (P 0.05, with 74% of participants having an improvement of 50%. Significant improvement in itching intensity also resulted in better quality of life, as there was also a significant reduction in median DLQI at weeks 2 and 4 of therapy compared with baseline (P 0.05), with 65% of patients having an improvement of 50% in median DLQI score.TENS may be an alternative safe treatment for LP-induced itching.

Background Atopic dermatitis (AD) is a chronic or chronically relapsing, eczematous, severely pruritic inflammatory skin disorder. Korean red ginseng (KRG) has been shown previously to exhibit diverse biological effects including anti-inflammatory and antipruritic effects in a murine model. Objective We aimed to investigate the beneficial effects of KRG on AD patients, to determine whether there was improvement in disease severity, skin barrier function, pruritus and sleep disturbance relief. Methods An open, noncomparative clinical study that utilized KRG tablets (500 mg/tablet) was conducted. This study included 41 patients with mild to moderate AD diagnosed by the Korean atopic dermatitis guidelines. Three visits to the hospital at days 1, 28±7, and 56±7 for evaluation were made. The effects of KRG were assessed by measuring eczema area and severity index (EASI) score, transepidermal water loss (TEWL), the visual analogue scale (VAS), total amount of topical agents used in recent 8 weeks and investigator global assessment (IGA). Results Patients taking KRG tablets showed significant decreases in EASI score and TEWL, and the VAS of pruritus and sleep disturbance were significantly reduced. The amount of topical agents used was reduced but not by a statistically significant amount. IGA at the third visit showed improvement of AD compared to the second visit, but the difference was not statistically significant. Conclusion KRG can be safely used as a health food to achieve clinical improvement of AD as well as improving overall quality of life, and has potential for further development.

Pruritus occurs in all patients with atopic dermatitis and requires quick relief to reduce disease exacerbation and improve quality of life. Crisaborole ointment is a non-steroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate atopic dermatitis. This post hoc analysis explores crisaborole ointment for early relief of pruritus in patients with mild to moderate atopic dermatitis from 2 phase III studies. Patients received crisaborole or vehicle twice daily for 28 days. Pruritus was graded on a 4-point scale of none (0) to severe (3). Early improvement in pruritus required a score of none (0) or mild (1), with a ≥ 1-grade improvement from baseline on day 6. Significantly more patients experienced early improvement in pruritus with crisaborole than with vehicle (56.6% vs 39.5%; p< 0.001), including at earliest assessment (day 2, 34.3% vs 27.3%; p = 0.013). Crisaborole is a topical treatment option that can rapidly relieve atopic dermatitis-associated pruritus.

Atopic dermatitis (AD) is a chronic and recurrent disease induced by underlying defects of the epidermal barrier and immunological disorders, typical of atopic diseases. The genetic and immunological mechanisms (outlined in the previous paper) affecting the dysfunction of the barrier are intensified by environmental factors, e.g. airborne and food allergens, infections and stress. For this reason, proper skin care, which prevents further damage and restores the epidermal barrier is of such importance in the field of AD therapy. Appropriate therapy is based on emollients which, coupled with anti-inflammatory and antipruritic treatment, should be used as the first-line therapy. The aim of the present paper is to outline the effects of the abovementioned factors on the dysfunction of the epidermal barrier as well as to emphasize the importance of proper atopic skin care in maintaining the integrity of the barrier and preventing exacerbation of the disease.

Background: Intrathecal morphine is commonly used for postcesarean analgesia. Its use is frequently associated with opioid-induced nausea, vomiting, and pruritus. Palonosetron (0.075 mg) combined with dexamethasone (8 mg) is postulated to have an additive effect over each drug alone. The study, therefore, compared the effect of intravenous (i.v.) palonosetron, dexamethasone, and palonosetron with dexamethasone combination in preventing intrathecal morphine-induced postoperative vomiting and pruritus in lower segment cesarean section (LSCS) patients. Settings and Design: Randomized, prospective, double-blinded, observational clinical study. Methods: Ninety pregnant women, American Society of Anesthesiologists physical status class I undergoing LSCS were included in the study. They were randomly assigned to three groups – Group P received 0.075 mg palonosetron i.v., Group D received dexamethasone 8 mg i.v., and Group PD received palonosetron 0.075 mg along with dexamethasone 4 mg i.v., just after spinal anesthesia with bupivacaine 2.2 ml (12 mg) and 150 μg morphine. The incidence of pruritus, nausea, vomiting, and need for rescue drug were recorded for 24 h. Statistical Analysis: Statistical analysis was performed using Student's t-test for categorical variables and Chi-square test for noncategorical variables. Results: The incidence of nausea, vomiting was significantly more in Group D (40%) than Group P (27%) and Group PD (20%) in 24 h. The incidence of pruritus was significantly more in Group D (6%) than Group P and PD (3%). The need of rescue antiemetic was more in Group D (30%) than Group P (6%) and Group PD (3%). No difference in three groups requiring rescue antipruritic drug. Conclusion: Prevention of intrathecal morphine-induced vomiting and pruritus was more effective with palonosetron alone or with dexamethasone combination than dexamethasone alone. Combination of palonosetron and dexamethasone proved no better than palonosetron alone.

Psoriasis is an immune-mediated chronic inflammatory skin disease characterized by erythema, scales, and infiltration of the skin, which causes deleterious effects on patient quality of life. TRP channel played important roles in the generation and conductance of itch signal . According to our results, psoriasis induced itch was TRPV4 dependent, and TRPV4 expression in both epidermis and DRG were up-regulated in psoriasis. Thus, TRPV4 is an attractive candidate for treating psoriasis induced itch. Cimifugin is a common compound in antipruritic Chinese medicine. In our study, GSK1016790A, a TRPV4 channel specific agonist, induced acute itch was inhibited by cimifugin in a dose-dependent manner. Furthermore, cimifugin treatment reduced the scratching behavior and reversed the TRPV4 up-regulation induced by psoriasis. In particular, cimifugin decreased GSK1016790A induced calcium response both in HaCaT cells and DRG neurons. Importantly, in TRPV4 transfected HEK293 cells, GSK101 induced calcium response was also significantly inhibited by cimifugin pretreatment. Consistent with our calcium imaging result, cimifugin pretreatment also inhibited GSK101 induced inward currents. Our study delineated a new role of TRPV4 in psoriasis and emphasized the antipruritic effect of cimifugin, which opened a new avenue to itch management in psoriasis.

The purpose of this review is to provide the current knowledge on antipruritic properties of IL-4/IL-13, IL-31, IL-17, and IL-23 antagonists in selected chronic skin conditions. Since pruritus is regarded as one of the most bothersome and unpleasant symptoms accompanying numerous inflammatory skin disorders, efforts are ongoing in the development of new treatment strategies capable of reducing its intensity thus improving the patients’ quality of life. Recent discoveries in targeted therapies and studies on pruritus have established that blockade of certain cytokines and/or pathways not only reduces the severity of skin involvement, but also shows a potent antipruritic activity. Considering a favorable safety profile of biologic drugs, their antipruritic properties are very promising and give a new hope for clinicians and the patients suffering from a number of itchy dermatoses. These recent findings clearly show that certain cytokines and their receptors may represent potential targets for innovative antipruritic drugs. Newer insights into the underlying pathogenesis of itch and identification of novel molecular pathways will undoubtedly promote the progress in the field of pruritus management.

Objective: To compare the therapeutic efficacy of topical ivermectin 0.5% vs. topical permethrin 5% cream in the treatment of scabies. Methods: This was open labelled, parallel group, prospective and comparative clinical study. Depending on the treatment to be received, there were two study groups comprising 50 patients each. Group 1 patients received topical 5 % Permethrin cream on day 1 and repeat application on 1st week follow up and if required then on second week; Group 2 patients received topical 0.5% Ivermectin cream on day 1 and repeat application on 1st week follow up and if required then on second week. The patient were also given antipruritic drug Tablet levocetirizine in a dose of 5 mg once daily given for 2 to 3 weeks. A total of 50 patients in each group were included in the study. Results: More than half of the patients in both Group 1 (56%) and Group 2 (54%) were below 30 years. More than half of the patients in both Group 1 (54%) and Group 2 (52%) were males. Majority of site of lesions were absent at 2 weeks in both the groups. Moderate and severe itching of lesion became nil at 2 weeks in both the groups. Grade 2 of itching of lesion was in 2% at 2 weeks in both the groups. KOH was positive in 94% patients in Group 1 and in 96% in Group 2 at baseline which decreased to 14% in Group 1 and 18% in Group 2 at 1 week. KOH positivity became nil at 2 weeks in both the groups. Conclusion: Topical Permethrin 5 % and Ivermectin 0.5 % were equally effective in the treatment of scabies up to 2 weeks.

Allergic rhinitis as one of the most common non-infectious respiratory inflammatory diseases is a global public health problem. The course of allergic rhinitis, its effect on the pathology of other organs and systems, the likelihood of complications and many other aspects of this pathology are largely determined by timely diagnosis and adequate treatment. At the heart of the pathogenesis of allergic rhinitis is the immediate allergic reaction. Histamine is the most important biogenic amine, the physiological regulator of the activity of various cells and systems and one of the main mediators of allergic reactions of immediate type. In the treatment of allergic rhinitis, one of the key places is occupied by antihistamines. One of such highly effective modern antihistamines is levocetirizine – a blocker of H1 histamine receptors of the second generation. Leveltzetirizine affects the histamine-dependent stage of allergic reactions, reduces vascular permeability and eosinophil migration, limits the release of inflammatory mediators, significantly influences the formation of edema of the tissues and the production of mucus, prevents development and greatly facilitates the course of the allergic reaction, has antiexudative, antipruritic and anti-inflammatory effects, and a pronounced ability to eliminate nasal obstruction in patients with seasonal allergic rhinitis. The drug levocetirizine Allerway®, bioequivalent to the original drug, is of definite interest to physicians of various specialties.

Chronic itch in inflammatory skin diseases, such as atopic dermatitis, markedly diminishes the quality of life of affected individuals. Comprehensive progress has been made in understanding itch signaling and associated mediators in the skin, dorsal root ganglia, spinal cord, and central nervous system, which may amplify or suppress atopic itch. Conventional therapies for atopic dermatitis are capable of reducing atopic itch; however, most patients are not satisfied with the antipruritic capacity of conventional treatments. Exploring itch pathways and mechanisms may lead to novel therapeutic approaches for atopic itch.

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.

Cooling is an effective temporary remedy for itch, bringing welcome relief to itchy insect bites, nettle stings, poison ivy, atopic dermatitis, and psoriasis. Menthol, causing a cooling sensation, has similar itch-relieving effects. Palkar et al. demonstrate that TRPM8, a menthol- and cold-activated ion channel, is essential for cooling to relieve itch, suggesting that pharmacologic TRPM8 activation should be explored further as an antipruritic strategy.

Animal studies have suggested that transient receptor potential (TRP) ion channels and G protein-coupled receptors (GPCRs) play important roles in itch transmission. TRPV3 gain-of-function mutations have been identified in patients with Olmsted syndrome which is associated with severe pruritus. However, the mechanisms causing itch remain poorly understood. Here, we show that keratinocytes lacking TRPV3 impair the function of protease activated receptor 2 (PAR2), resulting in reduced neuronal activation and scratching behavior in response to PAR2 agonists. Moreover, we show that TRPV3 and PAR2 were upregulated in skin biopsies from patients and mice with atopic dermatitis (AD), whereas their inhibition attenuated scratching and inflammatory responses in mouse AD models. Taken together, these results reveal a previously unrecognized link between TRPV3 and PAR2 in keratinocytes to convey itch information and suggest that a blockade of PAR2 or TRPV3 individually or both may serve as a potential approach for antipruritic therapy in AD.

The pathogenesis of itchy skin diseases including allergic contact dermatitis (ACD) is complicated and the treatment of chronic itch is a worldwide problem. One traditional Tibetan medicine, Qingpeng ointment (QP), has been used in treatment of ACD in China for years. In this study we used HPLC and LC/MS analysis, combined with a BATMAN-TCM platform, for detailed HPLC fingerprint analysis and network pharmacology of QP, and investigated the anti-inflammatory and antipruritic activities of QP on ACD induced by squaric acid dibutylester (SADBE) in mice. The BATMAN-TCM analysis provided information of effector molecules of the main ingredients of QP, and possible chronic dermatitis-associated molecules and cell signaling pathways by QP. In ACD mice, QP treatment suppressed the scratching behavior induced by SADBE in a dose-dependent manner and inhibited the production of Th1/2 cytokines in serum and spleen. Also, QP treatment reversed the upregulation of mRNAs levels of itch-related genes in the skin (TRPV4, TSLP, GRP, and MrgprA3) and DRGs (TRPV1, TRPA1, GRP, and MrgprA3). Furthermore, QP suppressed the phosphorylation of Erk and p38 in the skin. In all, our work indicated that QP can significantly attenuate the pathological alterations of Th1/2 cytokines and itch-related mediators, and inhibit the phosphorylation of MAPKs to treat the chronic itch.

Previous studies have suggested that acupuncture is effective for ameliorating itch intensity. However, factors associated with the antipruritic effects of acupuncture have yet to be clarified. In a randomized, sham-controlled, crossover trial, we investigated the antipruritic effects of acupuncture against histamine-induced itch in healthy volunteers. Autonomic changes using heart rate variability (HRV) and brain connectivity using functional magnetic resonance imaging (fMRI) were also assessed to identify physiological factors associated with the acupuncture response. Acupuncture significantly reduced itch intensity and skin blood perfusion as assessed by laser Doppler perfusion imaging compared to sham control, indicating the antipruritic effects of acupuncture. In responder and non-responder analysis, the power of normalized high frequency (HF norm) was significantly higher, while the power of normalized low frequency (LF norm) and LF/HF ratio were significantly lower in responders compared to non-responders, suggesting the acupuncture response involved parasympathetic activation. In fMRI analysis, the putamen and the posterior part of the midcingulate cortex (pMCC) were positively connected to itch and negatively correlated with itch intensity in responders. These results suggest that parasympathetic activity and functional connectivity of the putamen and pMCC could be associated with antipruritic response to acupuncture.

Pyrus ussuriensis Maxim. commonly known as "Sandolbae" in Korean is a pear tree widely distributed across East Asia. Recent studies indicate that P. ussuriensis Maxim. leaves (PUL) have antipruritic effects. This study aimed to determine the effects of PUL extract and its fractions in decreasing the itch sensation and skin lesions in two distinct animal models of atopic dermatitis (AD) induced by dinitrofluorobenzene (DNFB) or house dust mite (HDM). Our results showed that the total ethanol extract of PUL decreased the scratching behavior in mice with DNFB- and HDM-induced AD. Moreover, the ethyl acetate fraction of PUL significantly improved the overall condition of the mice with AD induced by HDM. Further, we used HEK293T cells that express receptors and ion channels for thymic stromal lymphopoietin (TSLP), a potent pruritogen for AD, to determine the mechanisms underlying the antipruritic effects of PUL extract/fractions. Specific subfractions of the PUL strongly inhibited the increase in calcium levels induced by TSLP. In addition, the specific subfraction of PUL inhibited the TSLP-induced increase in calcium levels in cultured mouse dorsal root ganglia neurons. Thus, our results showed that the PUL extract could be effective for alleviating pruritus, and the antipruritic effects were exerted probably via the inhibition of the TSLP pathway in peripheral sensory neurons governing the itch sensation in AD.

DergiPark: 541683 tmsj Aims: Cannabinoids are chemical compounds including natural cannabinoids found in the Cannabis plant, their synthetic counterparts, and endocannabinoids. Cannabidiol, a phytocannabinoid derived from the Cannabis plant, exerts anticonvulsant, anxiolytic, anti-inflammatory, neuroprotective, analgesic effects. Although there are many similarities between the pathophysiological mechanisms of pain and itch, researches that investigate the effect of cannabinoids on itching are insufficient. Here, we aimed to examine the antipruritic effect of cannabidiol and the contribution of spinal cannabinoid receptors. Methods: Male Balb/c mice, weighing 20-30 g, were used. Itching behavior was produced by intradermal injection of compound 48/80 (100 ?g/50 ?l); cannabidiol (1, 3, 10 mg/kg, ip) was administered 30 minutes before compound 48/80 injections. Then, scratching of the injected site by the hind paws was videotaped for 30 minutes. Locomotor performances were assessed using a rotarod apparatus. Results: Cannabidiol had no effect on compound 48/80-induced itching behavior at any dose given; moreover, cannabidiol did not produce any impairment on motor function. AM-251, a cannabinoid receptor type 1 antagonist, and AM-630, a cannabinoid receptor type 2 antagonist were administered intrathecally to observe the contribution of spinal cannabinoid receptors to the antipruritic action of cannabidiol. We observed that cannabidol did not possess any effect on itching behaviour. Conclusion: Our results indicate that systemic administration of cannabidiol does not attenuate compound 48/80 induced itching behavior in mice

Interleukin (IL)-31 is a cytokine involved in allergic inflammation which induces pruritus across species including dogs. Using recombinant canine IL-31 we have developed a model of pruritus in the dog to evaluate onset of action and duration of effect of therapeutic drugs.To assess the onset of action and duration of effect of lokivetmab (Cytopoint) in the IL-31-induced pruritus model.Twenty-four purpose-bred beagle dogs (neutered males, spayed and intact females) 1.5-4.7 years old and weighing between 6 and14 kg.Randomized, blinded, placebo-controlled studies were designed to evaluate the antipruritic properties of lokivetmab. Laboratory beagle dogs were given either placebo, 0.125, 0.5 or 2.0 mg/kg lokivetmab, subcutaneously. IL-31 then was administered to evaluate pruritus 3-5 h post-placebo or -lokivetmab administration as well as one, seven, 14, 28, 42 and 56 days post-dosing. Pruritus was evaluated over a 2 h window in animals by video monitoring and scored using a categorical scoring system.When animals were given 2.0 mg/kg lokivetmab, a significant reduction in pruritus was observed at 3-4, 4-5 and 3-5 h post-treatment (P ≤ 0.0001). When animals were given either 0.125, 0.5 or 2 mg/kg lokivetmab, the duration of effect was dose-dependent and statistically significant for 14, 28 and 42 days, respectively (P ≤ 0.0288).These data indicate that a single subcutaneous injection of 2 mg/kg lokivetmab produces a significant suppression of pruritus starting 3 h post-treatment that can be sustained for 42 days.L’interleukine (IL)-31 est une cytokine impliquée dans l’inflammation allergique qui induit le prurit pour toutes les espèces dont le chien. En utilisant un IL-31 recombinant nous avons développés un modèle de prurit chez le chien pour évaluer le début de l’action et la durée des effets des traitements.Déterminer le début d’action et la durée de l’effet du lokivetmab (Cytopoint) dans le modèle de prurit induit par IL-31.Vingt quatre chiens beagle de reproduction (mâles castrés, femelles stérilisées et entières) 1,5 - 4,7 ans et pesant de 6 à 14 kg. MÉTHODES: Les études contrôlées contre placebo, en aveugle, randomisées ont été étudiées pour évaluer les propriétés antiprurigineuses du lokivetmab. Les chiens beagle de laboratoire ont été attribués aux goupes placebo, 0.125, 0.5 ou 2.0 mg/kg de lokivetmab en sous-cutané. L’IL-31 a ensuite été administrée pour évaluer le prurit 3-5h après administration de lokivetmab ou de placebo ainsi que un, sept, 14, 38, 42 et 56 jours après dosage. Le prurit était évalué sur une fenêtre de 2h chez les animaux par monitoring vidéo et scoring utilisant un système d’évaluation catégorielle. RÉSULTATS: Quand les sujets ont reçu 2.0 mg/kg de lokivetmab, une diminution significative du prurit était observée à 3-4, 4-5 et 3-5h post traitement (P ≤ 0.0001). Quand les animaux recevaient soit 0.125 soit 0.5 ou 2 mg/kg de lokivetmab, la durée de l’effet était dépendant de la dose et statistiquement significatif, respectivement, pour 14, 28 et 42 jours (P ≤ 0.0288).Ces données indiquent qu’une unique injection sous-cutanée de 2 mg/kg de lokivetmab produit une suppression significative du prurit dès 3h après traitement et persiste pendant 42 jours.INTRODUCCIÓN: la interleuquina (IL)-31 es una citoquina involucrada en la inflamación alérgica que induce prurito en todas las especies, incluidos los perros. Utilizando IL-31 canina recombinante, hemos desarrollado un modelo de prurito en el perro para evaluar el inicio de la acción y la duración del efecto de los fármacos terapéuticos. OBJETIVO: evaluar el inicio de la acción y la duración del efecto de lokivetmab (Cytopoint) en el modelo de prurito inducido por IL-31. ANIMALES: Veinticuatro perros Beagle de laboratorio (machos castrados, hembras esterilizadas e intactas) de 1,5 a 4,7 años y con un peso de entre 6 y 14 kg. MÉTODOS: se diseñaron estudios aleatorios, ciegos y controlados con placebo para evaluar las propiedades antipruriginosas del lokivetmab. A los perros Beagle de laboratorio se les administró placebo, 0,125; 0,5 o 2,0 mg/kg de lokivetmab por vía subcutánea. Luego se administró IL-31 para evaluar el prurito 3-5 h después de la administración de placebo o lokivetmab, así como a uno, siete, 14, 28, 42 y 56 días después de la dosificación. El prurito se evaluó durante una ventana de 2 h en animales mediante monitorización por vídeo y se puntuó utilizando un sistema de puntuación categórico. RESULTADOS: cuando se administró a los animales 2,0 mg/kg de lokivetmab, se observó una reducción significativa del prurito a las 3-4, 4-5 y 3-5 h después del tratamiento (P ≤ 0,0001). Cuando se administró a los animales 0,125; 0,5 o 2 mg/kg de lokivetmab la duración del efecto fue dependiente de la dosis y estadísticamente significativa durante 14, 28 y 42 días, respectivamente (P ≤ 0,0288). CONCLUSIÓN: estos datos indican que una sola inyección subcutánea de 2 mg/kg de lokivetmab produce una supresión significativa del prurito a partir de las 3 h posteriores al tratamiento que se mantiene durante 42 días.Interleukin (IL)-31 ist ein Zytokin, welches bei der allergischen Entzündung involviert ist und Juckreiz bei allen Spezies wie auch beim Hund auslöst. Wir haben beim Hund ein Juckreiz Modell entwickelt, wobei wir eine rekombinante Form von caninem IL-31 verwendet haben, um den Wirkungseintritt und die Dauer der Wirkung dieser therapeutischen Medikamente zu evaluieren. ZIEL: Die Beurteilung des Wirkungseintritts und der Wirkungsdauer von Lokivetmab (Cytopoint) beim durch IL-31 induzierten Juckreizmodell.Vierundzwanzig zu diesem Zweck gezüchtete Beagles (kastrierte Rüden, kastrierte und intakte Hündinnen), im Alter von 1,5 - 4,7 Jahren, mit einem Gewicht zwischen 6 und 14 kg.Es wurden randomisierte, geblindete, Plazebo-kontrollierte Studien designed, um die juckreizstillenden Eigenschaften von Lokivetmab zu evaluieren. Laborbeagles wurde entweder Plazebo oder 0,125; 0,5 oder 2,0 mg/kg Lokivetmab subkutan verabreicht. IL-31 wurde verabreicht, um den Juckreiz 3-5h Post-Plazebo oder -Lokivetmab Verabreichung zu evaluieren, sowie nach einem, sieben, 14, 28, 42 und 56 Tage post-Administration. Der Juckreiz wurde über ein 2-stündiges Fenster evaluiert, wobei die Tiere mittels Videoüberwachung und mit Hilfe eines kategorischen Systems bewertet wurden.Wenn den Tieren 2,0 mg/kg Lokivetmab verabreicht wurde, konnte eine signifikante Reduktion des Pruritus 3-4, 4-5 und 3-5 h nach der Behandlung (P ≤ 0,0001) beobachtet werden. Wenn den Tieren entweder 0,125; 0,5 oder 2 mg/kg Lokivetmab verabreicht wurde, war die Wirkungsdauer Dosis-abhängig und für 14, 28 bzw 42 Tage statistisch signifikant (P ≤ 0,0288).Diese Ergebnisse zeigen, dass eine einzige subkutane Injektion von 2 mg/kg Lokivetmab eine signifikante Unterdrückung des Juckreizes bewirkt, welche 3h nach der Administration beginnt und 42 Tage lang anhält.背景: インターロイキン (IL)-31 はアレルギーによる炎症に関与するサイトカインであり、犬を含む様々な種の掻痒を誘発する。我々は、イヌ IL-31 を用いて、犬の掻痒モデルを開発し、治療薬の作用発現および効果持続時間を評価した。 目的: 本研究の目的は、IL-31誘発性掻痒モデルにおけるロキベトマブ (サイトポイント) の作用発現および効果持続時間を評価することであった。 被験動物: 1.5˜4.7歳、体重6˜14kgの24頭の実験ビーグル犬 (去勢済みオス、去勢済みメス、未避妊メス) 。 方法: ロキベトマブの抗掻痒特性を評価するため、無作為化盲検プラセボ対照試験を実施した。実験用ビーグル犬にプラセボ、0.125、0.5または2.0mg/kgのロキベトマブを皮下投与した。その後、IL-31を投与し、プラセボまたはロキベトマブ投与3˜5時間後、および投与1日後、7日後、14日後、28日後、42日後、56日後の掻痒を評価した。掻痒は、ビデオモニタリングにより動物を2時間評価し、カテゴリカルスコアリングシステムを用いて点数化した。 結果: 被験動物に2.0 mg/kgのロキベトマブを投与した場合、掻痒の有意な減少が3-4、4-5および3-5時間後に観察された (P≦0.0001) 。動物に0.125、0.5または2mg/kgのロキベトマブを投与した場合、効果の持続期間はそれぞれ14日、28日および42日で用量依存的であり、統計的に有意であった (P≦0.0288) 。 結論: これらのデータは, 2mg/kgのロキベトマブを単回皮下注射することで, 治療後3時間後から掻痒が有意に抑制され, その効果は42日間持続することを示している。.背景: 白细胞介素(IL)-31是一种参与过敏性炎症的细胞因子, 可在包括犬等多物种体内诱导瘙痒。使用重组犬IL-31, 我们开发了犬瘙痒模型, 以评价治疗药物的起效时间和作用持续时间。 目的: 评估洛基维特单抗(赛妥敏)在IL-31诱导瘙痒模型中的起效时间和作用持续时间。 动物: 24只专门饲养的比格犬 (去势雄性、切除卵巢和完整雌性) , 1.5-4.7岁, 体重6-14 kg。 方法: 随机、设盲、安慰剂对照研究旨在评价洛基维特单抗的止痒特性。实验室比格犬经皮下给予安慰剂、0.125、0.5或2.0 mg/kg 洛基维特单抗。然后给予IL-31,以评价安慰剂或洛基维特单抗给药后3-5h以及给药后1、7、14、28、42和56天的瘙痒。通过视频监测在2h窗口内评价动物的瘙痒, 并使用分类评分系统进行评分。 结果: 当给予动物2.0 mg/kg 洛基维特单抗时, 在给药后3-4、4-5和3-5 h观察到瘙痒显著减轻(P≤0.0001)。当给予动物0.125、0.5或2 mg/kg 洛基维特单抗时, 作用持续时间呈剂量依赖性, 分别为14、28和42天, 具有统计学显著性(P≤0.0288)。 结论: 这些数据表明, 2 mg/kg 洛基维特单抗单次皮下注射给药后3h开始显著抑制瘙痒, 并能持续42天。.A interleucina (IL) -31 é uma citocina envolvida na inflamação alérgica que induz prurido em várias espécies, incluindo cães. Utilizando IL-31 canina recombinante, desenvolvemos um modelo de prurido em cães para avaliar o início da ação e a duração do efeito de drogas terapêuticas.Avaliar o início de ação e a duração do efeito do lokivetmab (Cytopoint) no modelo de prurido induzido por IL-31.Vinte e quatro cães beagle criados para fins específicos (machos castrados, fêmeas esterilizadas e intactas) com 1,5-4,7 anos de idade e pesando entre 6 e 14 kg. MÉTODOS: Estudos randomizados, cegos e placebo-controle foram elaborados para avaliar as propriedades antipruriginosas do lokivetmab. Os cães beagle de laboratório receberam placebo, 0,125, 0,5 ou 2,0 mg/kg de lokivetmab, por via subcutânea. A IL-31 foi então administrada para avaliar o prurido 3-5 h após a administração de placebo ou lokivetmab, bem como um, sete, 14, 28, 42 e 56 dias após a administração. O prurido dos animais foi avaliado através de monitoramento por vídeo ao longo de uma janela de 2h e pontuado usando um sistema de pontuação categórica.Quando os animais receberam 2,0 mg/kg de lokivetmab, uma redução significativa do prurido foi observada em 3-4, 4-5 e 3-5h após o tratamento (P ≤ 0,0001). Quando os animais receberam 0,125, 0,5 ou 2 mg/kg de lokivetmab, a duração do efeito foi dependente da dose e estatisticamente significativa durante 14, 28 e 42 dias, respetivamente (P ≤ 0,0288). CONCLUSÃO: Esses dados indicam que uma única injeção subcutânea de 2 mg/kg de lokivetmab produz uma supressão significativa do prurido começando 3 horas após o tratamento, que é mantida por 42 dias.