Treatment Of Itch Research Articles

Comparing doxepin cream to oral antihistamines for the treatment of itch in burn patients: A multi-center triple-blind randomized controlled trial

BackgroundDoxepin cream, an antihistaminic agent, has shown promising results in the treatment of pruritus in burn patients. However, its effectiveness has not been studied comprehensively. ObjectiveTo evaluate whether doxepin cream is more effective than oral antihistamines in reducing pruritus. MethodsWe performed a multicenter triple-blind randomized controlled trial of twelve weeks randomizing burn patients ≥18 years with an itch intensity ≥3 on a Visual Analogue Scale (VAS) between doxepin hydrochloride 5% cream with placebo tablet or oral antihistamine (clemastine) with placebo cream. Primary endpoint was change in itch intensity. Secondary endpoints included impact of itch (Burn Itch Questionnaire), quality of life (SF-36), somnolence, and erythema (DermaSpectrometer). ResultsThirty-one (of the intended 108) subjects could be included: 13 were randomized to the doxepin and 18 to the clemastine group. The skewed distribution is attributable to the low inclusion rate. Both groups showed a significant reduction in itch intensity over a period of twelve weeks (doxepin p = 0.043, clemastine p = 0.019) with no difference between both groups in: mean itch intensity difference (p = 0.199), any of the domains (p = 0.940, p = 0.698, p = 0.859) of the Burn Itch Questionnaire, quality of life, somnolence (p = 0.143) and erythema (p = 0.796). ConclusionThe effectiveness of doxepin cream was similar to oral antihistamines in reducing itch. However, considering the study ’s limitations, a superior effect of doxepin cream cannot be completely ruled out. We recommend that future studies use a cross-over design so fewer inclusions are needed to obtain adequate power.

Commiphora myrrha inhibits itch-associated histamine and IL-31 production in stimulated mast cells.

Commiphora myrrha (Myrrh) is widely recognized for its anti-inflammatory and antimicrobial properties, which are utilized for the treatment of oral ulcers, gingivitis, sinusitis, glomerulonephritis, brucellosis and a variety of skin disorders. The current study aimed to assess whether myrrh modulates itch-associated interleukin (IL)-31 cytokine production and histamine release in stimulated human mast cells (HMC-1). To realize this, molecular biology techniques including real-time quantitiative PCR, western blotting and ELISA were employed. The results indicated that Myrrh successfully suppressed phorbol myristate acetate and calcium ionophore-stimulated mRNA expression, and reduced the production of IL-31 in HMC-1 cells. In addition, myrrh served as a suppressor of extracellular signal-regulated kinase and NF-κB activation, indicating its mechanism in the prevention of HMC-1 cell IL-31 production. Myrrh also prevented the release of histamine in HMC-1 cells. Whilst the present study awaits in vivo support, the pharmacological actions of myrrh provide new indications as to its potential applicability for itch treatment, which cannot be treated with histamine receptor blockers alone.

A systematic review of questionnaires on itch by the Special Interest Group “Questionnaires” of the International Forum for the Study of Itch (IFSI)

Introduction: Itch can be perceived differently across patients and it can affect daily life in various ways. It is essential to assess those aspects that are relevant for the individual patient’s needs to improve treatment of patients suffering from acute or chronic itch. The International Forum for the Study on Itch (IFSI) Special Interest Group on “Questionnaires” aims to propose tools to assess different dimensions of itch and improve patient care. As a first step, this study aimed at a systematically reviewing existing patients’ self-report questionnaires on itch. Materials and methods: The databases PubMed, PsycINFO, and CINAHL were systematically searched for any scientific publication describing patients’ self-report questionnaires that assess itch-related information (≥2 items). Information about the publication was extracted by 2 experts as well as which of the 14 predefined dimensions of itch (by the IFSI Special Interest Group) were assessed within the questionnaire, for instance, duration of itch, itch aggravating or relieving factors, and effects on quality of life. Results: From a total of 5282 records, 58 articles were derived describing 62 questionnaires. Over half of the questionnaires were developed for dermatological conditions, and the vast majority targeted at adults. Most questionnaires address itch-related disability and itch intensity. Affective qualities of itch, coping with itch, response to current itch treatment, and the opinion on the origin of itch are infrequently asked for. Discussion: The number and content of the items within a dimension vary greatly. Measurement properties of the questionnaires were not systematically addressed, as these were often not reported in the original publication. Future research should focus on selecting adequate and reliable (sub)scales to develop a modular questionnaire system in order to uniformly assess the individual patient’s demands and improve care.

Reasons for Underreporting of Uremic Pruritus in People With Chronic Kidney Disease: A Qualitative Study

ContextUremic pruritus, or itch, is common in people with chronic kidney disease (CKD) and has a negative impact on their lives and well-being. However, for reasons currently unknown, itch often remains unreported and therefore untreated. ObjectivesTo explore reasons for underreporting of itch to provide pointers for improving itch reporting and management in people with CKD. MethodsWe interviewed adult patients with CKD who self-reported experiencing itching in the last three years (n = 25), nephrologists (n = 10), and nurses (n = 12) from three kidney services in the U.K. Topic guides were informed by previous studies and a theoretical model of self-regulation. We conducted a thematic analysis of verbatim transcripts using framework analysis. ResultsWe identified the following three main themes reflecting factors that may influence whether itch is reported: knowledge on causes and treatment of itch (lack of awareness of the relationship between itch and CKD, and lack of knowledge of treatment options); attitudes toward importance of itch as a health issue (patients' and clinicians' attitudes); and prompts for itch assessment during consultations (routine practice, itch as a marker, and itch severity). ConclusionUnderreporting of itch is related to patients being unaware of its causes, accepting it as something to live with, prioritizing other health issues, and the length and timing of consultations. Health care professionals' assessment and management of itch vary widely and are not necessarily evidence-based. Better patient information, development of clinical practice guidelines, and incorporation of routine symptom assessments into care may improve itch reporting and management in people with CKD.

Emerging Treatments and Novel Pathways in Pruritus.

Itch treatment is a major challenge in the dermatologist's practice. We encounter patients suffering from pruritus on a regular basis, and often lack diverse treatment options to adequately respond to the patients' needs. In the last 20 years, novel pathways have been investigated that were beyond the scope of histamine. Although most did not result in a molecule available on the Canadian market, it is interesting and important as health care providers to stay up to date with new neuronal pathways involved in itch transmission and potential new therapeutic options. In this review, we will discuss pathways targeted in new topical treatments such as antagonist of proteinase-activated receptor-2, the endocannabinoid system, neurotrophins and tropomyosin-related kinase A receptor, the transient receptor potential-vanilloid or transient receptor potential-melastatine ion channels. New systemic therapies are now focusing on antagonizing the neurokinin receptor, modulating the opioidergic system, or targeting itch cytokines such as interleukin-31.

Long-term safety and efficacy of rupatadine in Japanese patients with itching due to chronic spontaneous urticaria, dermatitis, or pruritus: A 12-month, multicenter, open-label clinical trial

BackgroundRupatadine is a novel H1 antihistamine with platelet-activating factor antagonist activity. Its efficacy and safety on pruritic skin diseases have been demonstrated by 10mg/day rupatadine in a two weeks clinical trial. ObjectiveTo investigate the long-term efficacy and safety of rupatadine in the management of pruritus, and the clinical effect of updosing to 20mg in Japanese adult and adolescent patients. MethodsIn this 52-week, multicenter, open-label clinical trial (JapicCTI-152787), 206 patients (132, eczema or dermatitis; 58, pruritus; and 16, chronic spontaneous urticaria) received the study medication. The primary efficacy endpoint was change from baseline in the total pruritus score to Week 2 by treatment with rupatadine 10mg once daily. From Week 3 to Week 52, rupatadine updosing to 20mg was allowed. ResultsThe mean [95% CI] change from baseline to Week 2 in the total pruritus score was −1.241 [−1.450, −1.033] (paired t test, P< 0.001). The therapeutic effect persisted up to Week 52 (paired t test, P< 0.001). Adverse drug reactions (ADRs) were reported at an overall incidence of 18.0% (45 events in 37 patients). No serious or clinically significant ADRs were reported. Somnolence was the most common ADR (14.1%). ConclusionsThis clinical trial demonstrated the short- and long-term benefits of rupatadine in the management of patients with chronic spontaneous urticaria, dermatitis, and pruritus. Rupatadine 10 and 20mg doses are effective for the treatment of itch in adults and adolescents, and can be used safely on a long-term basis.

Pregabalin Treatment for RDEB Pain and Itch

Pregabalin Treatment for RDEB Pain and Itch

665 Pruritogen activation of human MRGPRX2

Histamine-independent mechanisms mediate the itch associated with the majority of dermatologic and systemic diseases. SLIGRL is a prototypic histamine-independent pruritogen. It is derived from the tethered sequence of the PAR2 receptor. Previous studies have demonstrated that SLIGRL activates mouse MrgprC11 to induce itch. We demonstrate that SLIGRL specifically activates human MRGPRX2, a receptor implicated in itch, allergy, and inflammation. We also evaluated the effect of QWF, an MRGPRX2 antagonist, on SLIGRL-induced activation of Mrgprs and SLIGRL-induced itch in mice. The in vitro interactions of SLIGRL and QWF with Mrgprs were studied using HEK-293 cells transfected with cDNAs encoding mouse MrgprC11, human MRGPRX1, MRGPRX2 MRGPRX3, and MRGPRX4. Intracellular calcium ([Ca2+]) was determined by ratiometric Fura-2 imaging as an indicator of receptor activation. For in vivo experiments, the mouse cheek model, which differentiates between itch and pain, was used to evaluate the effect of QWF on SLIGRL-induced itch in C57BL/6 mice. Consistent with previous studies, SLIGRL activates mouse MrgprC11. We demonstrate that SLIGRL specifically activates human MRGPRX2. The MRGPRX2 antagonist, QWF inhibits activation HEK-293 cells expressing mouse MrgprC11 and human MRGPRX2. SLIGRL-induced itch is significantly decreased (p<0.05), to baseline, with QWF. In conclusion, SLIGRL activates human MRGPRX2, a receptor implicated in itch, allergy, and inflammation. Receptor activation is blocked by QWF. Antagonists of human MRGPRX2 may have therapeutic role in the treatment of itch, allergy and inflammation.

Qingpeng Ointment Ameliorates Inflammatory Responses and Dysregulation of Itch-Related Molecules for Its Antipruritic Effects in Experimental Allergic Contact Dermatitis.

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.

Apigenin Inhibits IL-31 Cytokine in Human Mast Cell and Mouse Skin Tissues.

IL-31 is a recently discovered cytokine that is produced not only in T-cells but also in mast cells. It is strongly implicated to play a key role in inflammatory diseases and in the pathogenesis of itch in atopic dermatitis. Apigenin, a flavonoid of plant origin has numerous biological applications. In this study, we showed that apigenin modulates IL-31 mRNA, protein expression, and release in stimulated human mast (HMC-1) by inhibiting the phosphorylation activation of MAPK and NF-κB. To determine whether apigenin has similar effects in vivo, using Compound 48/80, we developed an atopic dermatitis itch model in mice and found an increase in IL-31 expression in the skin. We also revealed that apigenin prevents the infiltration and degranulation of mast cells and suppressed mRNA and protein expression of IL-31 in the skin of mice. These results provide a new suggestion of the potential applicability of apigenin for treatment of various inflammatory diseases and itch mediated by IL-31.

Aqueous and methanol extracts of Paullinia pinnata L. (Sapindaceae) improve inflammation, pain and histological features in CFA-induced mono-arthritis: Evidence from in vivo and in vitro studies.

Ethnopharmacological relevancePaullinia pinnata L. (Sapindaceae) is an African woody vine, traditionally used for the treatment of itch and pain-related conditions such as rheumatoid arthritis. AimThis work evaluates, in vitro and in vivo, the anti-inflammatory and analgesic effects of aqueous (AEPP) and methanol (MEPP) extracts from Paullinia pinnata leaves. MethodsAEPP and MEPP (100, 200 and 300 mg/kg/day) were administered orally in monoarthritic rats induced by a unilateral injection of 50 μl of Complete Freund's Adjuvant (CFA) in the ankle joint. During the 14 days of treatment, pain and inflammation were evaluated alternatively in both ankle and paw of the CFA-injected leg. Malondialdehyde (MDA) and glutathione (GSH) levels were assessed in serum and spinal cord. Histology of soft tissue of the ankle was also analyzed. For in vitro studies, AEPP and MEPP (10, 30 and 100 μg/ml) were evaluated against nitric oxide (NO) production by macrophages that were either non-stimulated or stimulated with LPS, 8-Br-AMPc and the mixture of both substances after 8 h exposure. These extracts were also evaluated on TNF-α and IL-1β production in cells stimulated with LPS for 8 h. Finally, the ability of the extracts to bind to neuroactive receptors was evaluated in vitro using competitive binding assays with >45 molecular targets. ResultsAEPP and MEPP significantly reduced by 20–98% (p < 0.001) the inflammation and pain sensation in both the ankle and paw. AEPP significantly increased glutathione levels (p < 0.05) in serum. Both extracts reduced MDA production in serum and spinal cord (p < 0.001), and significantly improved tissue reorganization in treated arthritic rats. P. pinnata extracts did not affect NO production in non-stimulated macrophages but significantly reduced it by 47–88% in stimulated macrophages. AEPP and MEPP also significantly inhibited TNF-α (35–68%) and IL-1β (31–36%) production in LPS stimulated macrophages. No cytotoxic effect of plant extracts was observed. MEPP showed concentration-dependent affinity for Sigma 2 receptors with an IC50 of 50 μg/ml. ConclusionThese results demonstrate the analgesic and anti-inflammatory effects of P. pinnata extracts on monoarthritis and further support its traditional use for pain and inflammation. These activities are at least partly due to the ability of these extracts to inhibit the production of NO, TNF-α, IL-1β and to likely modulate Sigma 2 receptors.

Medication rules of Professor Zhang Bing in treatment of skin itching based on data mining

Skin itching is a subjective sensation that causes the desire to scratch. It is one of the most common clinical symptoms at department of dermatology, even the only complaint of dermatological patients, which seriously affects the quality life of patients. Therefore, based on the software of traditional Chinese medicine inheritance auxiliary platform, association rules and complex system entropy clustering were adopted to collect and analyze Zhang Bing's prescriptions for skin itching, and get the drug use frequency and the relationship between drugs. Based on that, we could conclude the experience for skin itching. A total of 147 prescriptions were collected, 20 drugs with a frequency of 34 or more and 20 high-frequency drug combinations were analyzed, and 14 core combinations and 7 new prescriptions were excavated. The high-frequency drugs included Kochiae Fructus, Dictamni Cortex, Mori Cortex. The high-frequency drug combinations included "Kochiae Fructus-Dictamni Cortex" "Angelicae Dahuricae Radix-Chuanxiong Rhizoma" "Paeoniae Radix Rubra-Paeoniae Radix Alba", and the core combinations included "Schizonepetae Herba-Saposhnikoviae Radix-Cinnamomi Ramulus" "Arctii Fructus-Cicadae Periostracum-Houttuyniae Herba" "Ghrysanthemi Indici Flos-Kochiae Fructus-Dictamni Cortex", and new formulations include "Schizonepetae Herba, Saposhnikoviae Radix, Cinnamomi Ramulus, Clematidis Radix et Rhizoma, Tribuli Fructus, Dictamni Cortex", "Phellodendri Chinensis Coritex, Lonicerae Japonicae Flos, Atractylodis Rhizoma, Ghrysanthemi Indici Flos, Kochiae Fructus, Dictamni Cortex" "Arctii Fructus, Cicadae Periostracum, Houttuyniae Herba, Trichosanthis Fructus". The result of this research shows that Professor Zhang Bing's experience in the treatment of skin itching is mainly to dispelling wind and arresting itching, clearing heat and drying dampness.

Safety of cetirizine ophthalmic solution 0.24% for the treatment of allergic conjunctivitis in adult and pediatric subjects.

PurposeThe studies reported here aimed to assess the safety and tolerability of cetirizine ophthalmic solution 0.24%, a new topical ophthalmic medication approved by the US Food and Drug Administration for the treatment of ocular itching associated with allergic conjunctivitis.Patients and methodsThree clinical studies evaluated cetirizine ophthalmic solution 0.24% administration: a Phase I prospective, single-center, open-label, pharmacokinetic (PK) study (N=11) evaluating single-dose administration and twice-daily (BID) administration for 1 week in healthy adults, and two Phase III, multi-center, randomized, double-masked, vehicle-controlled, parallel-group studies evaluating the safety and tolerability in adult and pediatric populations (2–18 years of age) for up to 6 consecutive weeks. The first safety and tolerability study evaluated cetirizine BID (study 1, N=512), while the second study examined cetirizine three times daily (TID) (study 2, N=516). Each study assessed best corrected visual acuity, slit-lamp biomicroscopy, IOP, dilated ophthalmoscopy, treatment-emergent adverse events, vital signs, urine pregnancy test, and physical examination (general health, head, eyes, ears, nose, and throat). The PK study also measured hematology, blood chemistry, and urinalysis, while the two Phase III studies additionally assessed corneal endothelial cell counts (ECC) and ECC density in a subset of subjects (via specular microscopy), and drug administration tolerability.ResultsBilateral administration of cetirizine ophthalmic solution 0.24% resulted in low systemic exposure in the PK study and was associated with a low incidence of mild adverse events. There were no drug-related severe or serious adverse events. The tolerability scores between the active and vehicle groups were comparable, demonstrating high comfort in the administration of cetirizine ophthalmic solution 0.24%.ConclusionCetirizine ophthalmic solution 0.24% dosed BID or TID demonstrated an acceptable safety profile and was well-tolerated when administered to subjects aged ≥2 years.

Ethnobotany of Medicinal and Edible Plants of Tobelo Dalam Tribe in Aketajawe Lolobata National Park Area

This research aimed to find out local knowledge applied by the people of Tobelo Dalam tribe in the use of medicinal and edible plants. This research was carried out in Aketajawa Lolobata National Park at Aketajawe Block during April-June 2018. This research used a descriptive method through interviews and literature review. The selection of informants employed a snowball technique in which the main characteristics of the informants were the community leader, the traditional leader, and the community of the Tobelo Dalam Tribe. Data were analyzed using a qualitative analysis for data deepening on the ethnobotany study aspect based on the results of surveys and interviews obtained. The data were then analyzed using the Index of Cultural Significance (ICS) to determine the significance value of each plant species. The results showed that the number of plants used for treatment was 44 species dominated by those from the Malvaceae family such as achira or money tree (Pachira aquatica), cacao (Theobroma cacao), balacai or physic nut (Jatropha curcas L.) and dingo dingoto or climbing pandanus (Freycinetia sp). These plants are used for the treatment of mild wounds, allergic itching, postpartum and low stamina. Meanwhile, the number of edible plants often utilized by the people Tobelo Dalam Tribe was 7 species, covering Ipomoea batatas, Xanthosoma sp , Manihot utilisima, Oryza Sativa L ., Metroxylon sagu, and Colocasia esculenta . These edible plants derived from 5 families dominated by Aracaceae (33%), Euphorbiaceae (17%), Convolvulaceae (17%), and Palmae (16%). The utilized parts of the edible plants were tubers and pith. Keywords : Ethnobotany, Food, Medicine, Plant, Tobelo

Skin Barrier Damage and Itch: Review of Mechanisms, Topical Management and Future Directions.

Barrier damage, dry skin and itch are intricately linked and form the basis of many common skin diseases. Damage from environmental insults, or genetic or inflammatory causes, can impair the skin barrier, resulting in an increase in transepidermal water loss and activation of itch-associated nerve fibres. The itch-scratch cycle can perpetuate skin barrier damage and itch. Topical therapeutic strategies are utilised to overcome dry skin and itch, primarily in the form of emollients. Recent advances in our understanding of the mechanisms underlying itch have enabled the development of new topical therapies, which may be incorporated into existing treatment regimes. Ultimately, treatment of dry skin and itch must be highly tailored to the individual according to their needs.

Itch-associated Neuropeptides and Their Receptor Expression in Dog Dorsal Root Ganglia and Spinal Cord.

Most canine visits to veterinarians are related to skin diseases with itch being the chief complaint. Historically, several itch-inducing molecules and pathways have been identified in mice, but whether or not these are similar in dogs is not yet known. Herein, we set out to study the expression of pruritogenic neuropeptides, their cognate receptors with a limited functional validation thereof using a multidisciplinary approach. We demonstrated the expression of somatostatin and other major neuropeptides and receptors in canine dorsal root ganglia neurons. Next, we showed that interleukin-31, serotonin, and histamine activate such neurons. Furthermore, we demonstrated the physiological release of somatostatin from dog dorsal root ganglia neurons in response to several endogenous itch mediators. In summary, our results provide the first evidence that dogs use similar pruritogenic pathways to those characterized in mice and we thus identify multiple targets for the future treatment of itch in dogs.

The role of Nav1.7 and methylglyoxal-mediated activation of TRPA1 in itch and hypoalgesia in a murine model of type 1 diabetes.

Methylglyoxal (MGO), an endogenous reactive carbonyl compound, plays a key role in the pathogenesis of diabetic neuropathy. The aim of this study is to investigate the role of MGO in diabetic itch and hypoalgesia, two common symptoms associated with diabetic neuropathy.Methods: Scratching behavior, mechanical itch (alloknesis), and thermal hypoalgesia were quantified after intradermal (i.d.) injection of MGO in naïve mice or in diabetic mice induced by intraperitoneal (i.p.) injection of streptozotocin (STZ). Behavioral testing, patch-clamp recording, transgenic mice, and gene expression analysis were used to investigate the mechanisms underlying diabetic itch and hypoalgesia in mice.Results: I.d. injection of MGO evoked dose-dependent scratching in normal mice. Addition of MGO directly activated transient receptor potential ankyrin 1 (TRPA1) to induce inward currents and calcium influx in dorsal root ganglia (DRG) neurons or in TRPA1-expressing HEK293 cells. Mechanical itch, but not spontaneous itch was developed in STZ-induced diabetic mice. Genetic ablation of Trpa1 (Trpa1-/-), pharmacological blockade of TRPA1 and Nav1.7, antioxidants, and mitogen-activated protein kinase kinase enzyme (MEK) inhibitor U0126 abrogated itch induced by MGO or in STZ-induced diabetic mice. Thermal hypoalgesia was induced by intrathecal (i.t.) injection of MGO or in STZ-induced diabetic mice, which was abolished by MGO scavengers, intrathecal injection of TRPA1 blockers, and in Trpa1-/-mice.Conclusion: This study revealed that Nav1.7 and MGO-mediated activation of TRPA1 play key roles in itch and hypoalgesia in a murine model of type 1 diabetes. Thereby, we provide a novel potential therapeutic strategy for the treatment of itch and hypoalgesia induced by diabetic neuropathy.

Inflammatory mediators causing cutaneous chronic itch in some diseases via transient receptor potential channel subfamily V member 1 and subfamily A member 1.

Chronic itch with an itch–scratch vicious circle is a significant problem in a large amount of diseases. Some of these diseases, such as psoriasis, atopic dermatitis, prurigo nodularis, Sézary syndrome, uremic pruritus, diabetes and jaundice, are common. For a very long time, chronic itch has been a thorny problem with few effective treatments. Because of this, itch researchers and dermatologists seek to find the mechanisms among chronic itch, inflammatory cytokines and neurons. As an immediate area of research focus, we are going to find the peripheral cross‐talk between neurons and skin cells. Two receptors, named transient receptor potential channel vanilloid 1 and transient receptor potential channel ankyrin transmembrane protein 1, have been shown to play important roles in chronic itch. Many advances have been made so far this decade. This review talks about the updated mechanism of itch‐related inflammatory cytokines via transient receptor potential channels in cutaneous chronic itch and corresponding diseases. The search for itch‐related inflammatory mediators and the structure of transient receptor potential channels this decade could deepen our understanding of the mechanism of itch and help us find more treatments of chronic itch in the future.

Transcranial magnetic stimulation over contralateral primary somatosensory cortex disrupts perception of itch intensity.

Itch, a complex unpleasant sensation causing the desire to scratch, results from the activity of a network of brain regions. However, the specific functional contributions of individual regions within this network remain poorly understood. We investigated whether contralateral primary and secondary somatosensory cortices (S1, S2) and ipsilateral inferior frontal gyrus (IFG) are critically involved in the cortical processing of acute itch. Continuous theta burst transcranial magnetic stimulation (cTBS) was applied to either S1, S2 or IFG, followed by itch induction using a histamine prick. Results indicate a significant reduction in itch intensity when cTBS was applied to S1. Stimulation of S2 or the IFG was not associated with a significant reduction in itch intensity. The novel finding of an antipruritic effect elicited by disruption of activity in contralateral S1 suggests a causal role of S1 in encoding the sensory-discriminative aspect of itch and might be important in future studies on brain interventions for the treatment of itch.

PAR2 Pepducin-Based Suppression of Inflammation and Itch in Atopic Dermatitis Models

PAR2 has been proposed to contribute to lesion formation and intense itch in atopic dermatitis. Here, we tested the ability of a cell-penetrating pepducin, PZ-235, to mitigate the potentially deleterious effects of PAR2 in models of atopic dermatitis. PZ-235 significantly inhibited PAR2-mediated expression of inflammatory factors NF-κB, TSLP, TNF-α, and differentiation marker K10 by 94%-98% (P < 0.001) in human keratinocytes and suppressed IL-4 and IL-13 by 68%-83% (P < 0.05) in mast cells. In delayed pepducin treatment models of oxazolone- and DNFB-induced dermatitis, PZ-235 significantly attenuated skin thickening by 43%-100% (P < 0.01) and leukocyte crusting by 57% (P< 0.05), and it inhibited exvivo chemotaxis of leukocytes toward PAR2 agonists. Daily PZ-235 treatment of filaggrin-deficient mice exposed to dust mite allergens for 8 weeks significantly suppressed total leukocyte and T-cell infiltration by 50%-68%; epidermal thickness by 60%-77%; and skin thickening, scaling, excoriation, and total lesion severity score by 46%-56%. PZ-235 significantly reduced itching caused by wasp venom peptide degranulation of mast cells in mice by 51% (P < 0.05), which was comparable to the protective effects conferred by PAR2 deficiency. Taken together, these results suggest that a PAR2 pepducin may confer broad therapeutic benefits as a disease-modifying treatment for atopic dermatitis and itch.