Itch Sensation Research Articles

Molecular and cellular mechanisms of itch sensation and the anti-itch drug targets.

Itch is an uncomfortable feeling that evokes a desire to scratch. This protective reflex can effectively eliminate parasites that invade the skin. When itchy skin becomes severe or lasts for more than six weeks, it has deleterious effects on both quality of life and productivity. Despite decades of research, the complete molecular and cellular coding of chronic itch remains elusive. This persistent condition often defies treatment, including with antihistamines, and poses a significant societal challenge. Obtaining pathophysiological insights into the generation of chronic itch is essential for understanding its mechanisms and the development of innovative anti-itch medications. In this review we provide a systematic overview of the recent advancement in itch research, alongside the progress made in drug discovery within this field. We have examined the diversity and complexity of the classification and mechanisms underlying the complex sensation of itch. We have also delved into recent advancements in the field of itch mechanism research and how these findings hold potential for the development of new itch treatment medications. But the treatment of clinical itch symptoms still faces significant challenges. Future research needs to continue to delve deeper, not only to discover more itch-related pathways but also to explore how to improve treatment efficacy through multitarget or combination therapy.

Efficacy and safety of warm needle acupuncture for allergic rhinitis: A systematic review and meta-analysis with trial sequential analysis

BackgroundsWarm needle acupuncture is a distinct form of acupuncture therapy in which, after the needle is inserted into the acupoint, a lit moxa stick is placed on the needle's handle. ObjectiveThis research aims to provide evidence for efficacy and safety of warm needle acupuncture for allergic rhinitis. Search strategiesSeven online databases were searched for study collection, which were published up to March 15th, 2022. Keywords of searching included “AR”, “allergic rhinitis”, “anaphylactic rhinitis”, “warming needle”, “warming needle acupuncture”, “needle warming moxibustion”, “warm needle”, “warm needling method” and “warmed needle”. The quality of the included trials was assessed using the Cochrane risk of bias tool. InterventionsAmong the included trials, warm needle acupuncture—either alone or in combination with Western medicine or other acupoint-based therapies—served as the primary intervention for the experimental groups. In contrast, the control groups received treatments such as Western medicine alone, manual acupuncture alone, or a combination of electro and manual acupuncture. Systematic reviews and meta-analyses were conducted using RevMan 5.3, following the Cochrane systematic review methodology, while trial sequential analysis was performed with TSA 0.9. The quality of the findings was assessed using GRADEpro. ResultsFinally, 23 studies involving 2230 participants were covered. Results of this study revealed that warm needle acupuncture only, or with western medicine, or with other acupoint-based interventions were significantly superior to western medicine alone, manual acupuncture alone, or electro plus manual acupuncture for allergic rhinitis. Adverse events associated with warm needle acupuncture included sensations of chest tightness, throat itching, and allergic reactions to moxa smoke; however, these occurrences were not more frequent than those observed with Western medicine. There is need for RCTs of high quality with placebo or waitlist controls of the intervention for allergic rhinitis. ConclusionWarm needle acupuncture is with potential efficacy and is safe for patients with allergic rhinitis, but more trials are need for further confirmation of the evidence.

The involvement of keratinocytes in pruritus of chronic inflammatory dermatosis.

Frequent itching and incessant scratching are commonly observed in various chronic inflammatory skin conditions, including atopic dermatitis and psoriasis. The persistent and prolonged nature of pruritus can worsen one's quality of life. Keratinocytes (KCs), the predominant cells of the epidermis, have been confirmed to interact with sensory neurons and immune cells and be involved in chronic skin inflammatory diseases associated with pruritus. Initially, KCs and sensory neurons form a unique synapse-like connection within the epidermis, serving as the structural foundation for their interaction. Additionally, several receptors, including toll-like receptors and protease-activated receptor 2, expressed on KCs, become activated in an inflammatory milieu. On the one hand, activated KCs are sources of pro-inflammatory cytokines and neurotrophic factors, such as adenosine triphosphate, thymic stromal lymphopoietin, and nerve growth factor, which directly or indirectly participate in stimulating sensory neurons, thereby contributing to the itch sensations. On the other hand, KCs also function as primary transducers alongside intraepidermal nerve endings, directly initiating pruritic responses. This review summarizes the current literature and highlights the critical role of KCs in the development and persistence of chronic itch in inflammatory skin disorders.

LPS exacerbates TRPV4-mediated itch through the intracellular TLR4-PI3K signalling.

Pruritus is often accompanied with bacterial infections, but the underlying mechanism is not fully understood. Although previous studies revealed that lipopolysaccharides (LPS) could directly activate TRPV4 channel and TRPV4 is involved in the generation of both acute itch and chronic itch, whether and how LPS affects TRPV4-mediated itch sensation remains unclear. Here, we showed that LPS-mediated TRPV4 sensitization exacerbated GSK101-induced scratching behaviour in mice. Moreover, this effect was compromised in TLR4-knockout mice, suggesting LPS acted through a TLR4-dependent mechanism. Mechanistically, LPS enhanced GSK101-evoked calcium influx in mouse ear skin cells and HEK293T cells transfected with TRPV4. Further, LPS sensitized TRPV4 channel through the intracellular TLR4-PI3K-AKT signalling. In summary, our study found a modulatory role of LPS in TRPV4 function and highlighted the TLR4-TRPV4 interaction in itch signal amplification.

ASPEK NEUROSAINS DALAM PATOFISIOLOGI PRURITUS NOKTURNAL

Itching at night in scabies patients is considered a very disturbing symptom. It is known that the main role of the itch sensation and subsequent motor response is to remove environmental influences from the skin, especially arthropods. The purpose of this article is to provide an understanding of the overall physiology and associated pathophysiology of itch. This article focuses on the neuronal aspect, as the nervous system is necessary to perceive the sensation of itch, as well as the multidirectional connections between the nervous and immune systems that influence the transmission of itch from the skin to the spinal cord. Itching is felt by skin nerve fibers called pruriceptors. These primary afferent fibers function as antennae and continuously sense the skin environment to detect and respond to cues. All major afferents project to the dorsal part of the spinal cord. Peptidergic and nonpeptidergic neurons target different areas of the dorsal superficial lamina. Based on this review, it can be concluded that noxious and pruritic stimuli are mostly processed in the superficial dorsal horn, whereas deeper dorsal horn neurons receive nociceptive and pruritic input via polysynaptic innervation.

Unmet Needs in Darier's Disease from a Patient's Perspective: Lessons Learnt from the German Registry.

The MDHHgermany registry was initiated to characterize the "real-life" situation of affected individuals with Darier's disease (DD; Morbus Darier, MD) and Hailey-Hailey disease (HH), including their treatment and healthcare. To gain deeper insights into medical care of patients with DD, various aspects such as demographics, subjective symptoms, patient satisfaction with medical care, past and current therapies were explored. Patients with diagnosed DD were included. Subjective symptoms such as itch, pain and burning sensation were assessed. Individual therapy goals were recorded and patients assessed previous/current therapies along with satisfaction of medical care and treatment. A total of 55 patients were recruited; 47 patients were eligible for the analysis. Pruritus was rated the most bothersome symptom. Some 42.6% had not received systemic treatment so far or systemic therapies were rated ineffective (32.6%). Most commonly oral retinoids were prescribed, followed by corticosteroids. Patient satisfaction with medical care and treatment proved to be mediocre. This "real-life" data show an alarming unmet need regarding patients' satisfaction with medical care and treatment, evidenced by the reported lack of disease control. Further studies and interventions are needed to improve the spectrum of available therapies. MDHHgermany provides a foundational platform for future clinical trials, epidemiological studies, and pathophysiological analyses.

Region-specific activation in the accumbens nucleus by itch with modified scratch efficacy in mice – a model-free multivariate analysis

Itch is a protective/defensive function with divalent motivational drives. Itch itself elicits an unpleasant experience, which triggers the urge to scratch, relieving the itchiness. Still, it can also result in dissatisfaction when the scratch is too intense and painful or unsatisfactory due to insufficient scratch effect. Therefore, it is likely that the balance between the unpleasantness/pleasure and satisfaction/unsatisfaction associated with itch sensation and scratching behavior is determined by complex brain mechanisms. The physiological/pathological mechanisms underlying this balance remain largely elusive. To address this issue, we targeted the "reward center" of the brain, the nucleus accumbens (NAc), in which itch-responsive neurons have been found in rodents. We examined how neurons in the NAc are activated or suppressed during histamine-induced scratching behaviors in mice. The mice received an intradermal injection of histamine or saline at the neck, and the scratching number was analyzed by recording the movement of the bilateral hind limbs for about 45 min after injection. To experimentally manipulate the scratch efficacy in these histamine models, we compared histamine's behavioral and neuronal effects between mice with intact and clipped nails on the hind paws. As expected, the clipping of the hind limb nail increased the number of scratches after the histamine injection. In the brains of mice exhibiting scratching behaviors, we analyzed the expression of the c-fos gene (Fos) as a readout of an immediate activation of neurons during itch/scratch and dopamine receptors (Drd1 and Drd2) using multiplex single-molecule fluorescence in situ hybridization (RNAscope) in the NAc and surrounding structures. We performed a model-free analysis of gene expression in geometrically divided NAc subregions without assuming the conventional core–shell divisions. The results indicated that even within the NAc, multiple subregions responded differentially to various itch/scratch conditions. We also found different clusters with neurons showing similar or opposite changes in Fos expression and the correlation between scratch number and Fos expression in different itch/scratch conditions. These regional differences and clusters would provide a basis for the complex role of the NAc and surrounding structures in encoding the outcomes of scratching behavior and itchy sensations.

Ozonated Hydrotherapy Combined with LED Yellow Light Irradiation and Oral Minocycline Treatment for Mild to Moderate Papulopustular Rosacea: A Comparative Retrospective Study.

The treatment of recurrent rosacea has always been a problem. Oral minocycline has been widely used in the treatment of rosacea. However, the efficacy and safety of ozonated hydrotherapy combined with LED yellow light irradiation and oral minocycline for mild to moderate papulopustular rosacea (PPR) has not been thoroughly studied. Patients with rosacea who met the criteria and had complete clinical statistic admitted to our hospital from April 2021 to September 2022 were retrospectively collected and divided into combined therapy group and oral only group. The patients in the two groups were treated with minocycline for 8 weeks. In addition, the patients in combined therapy group were treated with ozone hydrotherapy once a week, followed by LED yellow light irradiation for a total of 4 weeks. The Investigator' s global assessment (IGA) score was used to assess the condition. The efficacy was evaluated using the patients' subjective symptom scores. Skin lesion images and adverse reactions were recorded. The recurrence rate was observed after 24 weeks of follow-up. A total of 39 patients included in the study. After 4 weeks of treatment, the effective rate was 90% in combined therapy group and 52.63% in oral only group (p<0.05). After 8 weeks of treatment, the total score of the patients' subjective symptom scores and the scores of itching and burning sensation in combined therapy group were lower than those in oral only group (p<0.05). After 24 weeks of follow-up, the recurrence rate of combined therapy group was 5%, and that of oral only group was 26.32%. The mild adverse reactions experienced by both groups disappeared during follow-up. This combination therapy has a significant, rapid and safe therapeutic effect, especially in relieving itching and burning sensations, and may reduce the recurrence rate.

A phytosphingosine derivative mYG-II-6 inhibits histamine-mediated TRPV1 activation and MRGPRX2-dependent mast cell degranulation

BackgroundPhytosphingosine and its derivative are known for their skin-protective properties. While mYG-II-6, a phytosphingosine derivative, has shown anti-inflammatory and antipsoriatic effects, its potential antipruritic qualities have yet to be explored. This study aimed to investigate mYG-II-6′s antipruritic properties. MethodsThe calcium imaging technique was employed to investigate the activity of ion channels and receptors. Mast cell degranulation was confirmed through the β-hexosaminidase assay. Additionally, in silico molecular docking and an in vivo mouse scratching behavior test were utilized. ResultsUsing HEK293T cells transfected with H1R and TRPV1, we examined the impact of mYG-II-6 on histamine-induced intracellular calcium rise, a key signal in itch-mediating sensory neurons. Pretreatment with mYG-II-6 significantly reduced histamine-induced calcium levels and inhibited TRPV1 activity, suggesting its role in blocking the calcium influx channel. Additionally, mYG-II-6 suppressed histamine-induced calcium increase in primary cultures of mouse dorsal root ganglia, indicating its potential antipruritic effect mediated by histamine. Interestingly, mYG-II-6 exhibited inhibitory effects on human MRGPRX2, a G protein-coupled receptor involved in IgE-independent mast cell degranulation. However, it did not inhibit mouse MrgprB2, the ortholog of human MRGPRX2. Molecular docking analysis revealed that mYG-II-6 selectively interacts with the binding pocket of MRGPRX2. Importantly, mYG-II-6 suppressed histamine-induced scratching behaviors in mice. ConclusionsOur findings show that mYG-II-6 can alleviate histamine-induced itch sensation through dual mechanisms. This underscores its potential as a versatile treatment for various pruritic conditions.

Implications of Emulating a Dermatologist: A Study of Topical medication usage for dermatoses prescribed by Non-Dermatologists in a rural area

Introduction: Over-the-counter (OTC) medications refer to drugs that a patient can purchase without prescription from a registered medical practitioner. Topical OTC medication usage for skin disorders is common in rural India, due to non-availability of Dermatologists. Inappropriate use of such drugs has resulted in various cutaneous adverse effects and antifungal resistance. Aims: To determine the pattern of usage of the different OTC topical medications for various Dermatological indications, their source of prescription and their cutaneous adverse effects. Materials and Methods: Patients presenting to Dermatology OPD with a history of usage of topical OTC drugs for skin disorders were recruited. Details such as type of OTC drug used, the source of its prescription, indications for which it was advised and patients knowledge regarding steroids were documented. Patients were examined for cutaneous adverse effects. Results: Out of 100 patients there were 46 males and 54 females. Dermatophytosis (29%) was the most common indication for which these drugs were used. The common side effects were itching (17.86%) and burning sensation (13.39%). Majority of the drugs were advised by pharmacists (36%) followed by friends and relatives (29%). Betamethasone was the commonest steroid and Betnovate was the commonest brand misused. Majority (97%) of the patients were unaware of topical steroids and their adverse effects. Conclusion: The growing threat of OTC drug abuse is evident from our study. Stringent drug control policies are required to regulate the sale of topical OTC drugs. Creating awareness among patients and General physicians about the adverse effects of OTC topical medications including steroids is truly the need of the hour.

Verbal expressions describing itch quality in atopic dermatitis and urticaria: an online questionnaire survey in Japan

Background: The nature of itch sensation varies depending upon the patient and the disease. However, few studies have focused on verbal expressions describing itch of atopic dermatitis (AD) in quality.Objectives: To investigate itch quality in patients with AD compared with that of urticaria.Methods: We conducted an online questionnaire survey describing itch experiences in June 2021. Participants were Japanese patients who had visited hospitals for their consultations and treatments of AD or urticaria in the last 6 months, and 295 and 290 responses, respectively, to questions using 12 terms describing itch quality were analyzed.Results: The most suitable expression describing intense itch that patients could not help scratching differed between the diseases, where most AD patients selected “muzumuzu” (a mimetic word for creepy–crawly itch) (27%) or “painful itch” (20%), and most urticaria patients selected “muzumuzu” (24%) or “itch like mosquito bites” (22%). The most suitable expressions describing itch that would make patients happiest if improved was “painful itch” (27%) in AD patients, significantly higher than urticaria patients (19%). More AD patients (55%) responded that they sometimes felt itch even after the skin symptoms had subsided than urticaria patients (41%). The most suitable expression of remnant itch selected was “muzumuzu” for AD (58/161 patients, 36%) and urticaria (29/120 patients, 24%).Conclusion: The quality of itch sensations can be classified not only between diseases but also during the clinical course of each disease. Significant expressions that patients with AD use to describe itch sensations could promote more appropriate treatment for itch.

Measuring itch occurrence in various chronic pain conditions: across sectional study

Aim: The relationship between chronic pain conditions and itch occurrence has been studied; however, reports on itch among patients with different chronic pain conditions are limited. It is also unclear how pain medications affect itch experienced alongside chronic pain. The primary aim of the current study is primary aim is to investigate the occurrence of itch among patients with various chronic pain conditions, and the secondary aim is to assess the impact of pain medication on itch episodes. Methods: In the initial quarter of 2019, three hundred seventeen patients with chronic pain conditions were followed up at Hamad medical corporation (HMC)’s pain clinics. Of these, 285 met the study criteria and consented to participate. For patients who reported itch during the routine pain assessment, the 5-D score was utilized for the itch evaluation. The effect of pain medications on itch was also documented. Results: Among the 285 patients, 41 (14.4%) reported experiencing an itchy sensation. Out of those 41 patients, 31 (75.6%) were diagnosed with neuropathic pain. This condition was found to be significantly associated with itch (P &lt; 0.0001) compared to other conditions such as musculoskeletal (MSK) and fibromyalgia/myofascial pain, which accounted for only 12% of those who reported itch. Moreover, 25 (60.97%) of the patients with itch reported that they experienced concomitant itch sensations with pain episodes. Notably, 28 patients (68.3%) responded positively to pain medication. Furthermore, the study identified a significant correlation between the duration of pain and the incidence of itch (P &lt; 0.0001). Conclusions: The current study findings highlight neuropathic pain as the most prevalent chronic pain condition associated with itch. Additionally, the duration of pain was found to impact itch incidence.

Deciphering the enigma of itch sensation: insights and impact from a readability study.

Itch terminology is ambiguous. How itch was described in online materials and how terminology influenced the readability of these materials was previously unknown. Two groups of search terms, itch and prurigo, were translated into five of the most prevalent European Union (EU) languages. The itch group consisted of "itch" and "pruritus." The prurigo group consisted of "prurigo," "prurigo nodularis," and "chronic prurigo". Then, a search of the terms in each language was queried in the Google search engine in the private mode of the Internet browser. The first 50 results generated were assessed for suitability. Patient education was the primary objective of the materials provided, with no barriers or advertisements included. In cases where the terms yielded identical outcomes, any duplicated materials were omitted from the analysis. When translating search terms within a group led to just one shared transcription, the results were attributed to the search term with the most similar syntax. The Lix score was utilized to assess readability. 314 articles in English, German, Italian, French, and Spanish were evaluated. The term "pruritus" was the most commonly used description for the sensation of itching, with 142 (45%) articles included. Overall, the mean Lix score was 54 ± 9, classifying all articles as hard to comprehend. Articles in the itch group had significantly (P < 0.001) lower mean Lix score (52 ± 9) than materials in the prurigo group (56 ± 10). Despite being more accessible to conceptualize, skin conditions such as prurigo had lower readability compared to information about the itch itself. The distinction between "itch" and "pruritus" was unclear.

Role of Sheeta Upanaha in the Management of Vipadika – A Case Study

Skin is the mirror which reflects the harmony of Internal functions of body. Psoriasis is a non-infective inflammatory, Proliferative, Chronic skin disease in which there are scaly papules and plaques that can involve any part of body. Palmoplantar psoriasis refers to psoriasis that develops on palms and soles. Vipadika is included in Kshudra kusta having sign and symptoms similar to Palmoplantar psoriasis. In this case study, A 65-year-old male patient a known case of Palmoplantar psoriasis approached with symptoms of Scales and fissures over both palms and soles with Pain, Severe itching and burning sensation for the past 1year. After clinical examination and history of the patient he was advised, Deepana &amp; Pachana, Shamana Snehapana and Seetha Upanaha as module of treatment. Even though treatment principles such as Deepana, Pachana, Shamana Snehapana might have helped in the overall result, but it was Seetha Upanaha Chikitsa observed to be quite significant in this case, as patient started feeling better after starting of Seetha upanaha. After implementation of treatment plan patient has become completely symptom free and there was no recurrence even after six months.

Spinal Glycine Receptor Alpha 3 Cells Communicate Sensations of Chemical Itch in Hairy Skin.

Glycinergic neurons regulate nociceptive and pruriceptive signaling in the spinal cord, but the identity and role of the glycine-regulated neurons are not fully known. Herein, we have characterized spinal glycine receptor alpha 3 (Glra3) subunit-expressing neurons in Glra3-Cre female and male mice. Glra3-Cre(+) neurons express Glra3, are located mainly in laminae III-VI, and respond to glycine. Chemogenetic activation of spinal Glra3-Cre(+) neurons induced biting/licking, stomping, and guarding behaviors, indicative of both a nociceptive and pruriceptive role for this population. Chemogenetic inhibition did not affect mechanical or thermal responses but reduced behaviors evoked by compound 48/80 and chloroquine, revealing a pruriceptive role for these neurons. Spinal cells activated by compound 48/80 or chloroquine express Glra3, further supporting the phenotype. Retrograde tracing revealed that spinal Glra3-Cre(+) neurons receive input from afferents associated with pain and itch, and dorsal root stimulation validated the monosynaptic input. In conclusion, these results show that spinal Glra3(+) neurons contribute to acute communication of compound 48/80- and chloroquine-induced itch in hairy skin.

Efficacy of green tea ( Camellia sinensis Linn) 3% extract cream on improvement of striae distensae.

Striae distensae (SD) is a skin condition that frequently causes dermatological consultations and although asymptomatic, it may can cause itch and burning sensation. Green tea extract contains polyphenol, including flavanol, flavandiol, flavonoid, phenolic acid, amino acids and minerals which play a role in the repair of stretch marks through anti-inflammatory mechanism, increase collagen production, fibroblast proliferation, and skin hydration. To determine the efficacy of green tea extract cream on striae distensae. This is a pre-experimental clinical trial with a pretest-posttest design on 36 subjects with striae distensae. Diagnosis establishes through history taking and clinical evaluation. Imam Nelva Alviera (INA) score was used as SD severity before and after the application of the 3% green tea extract cream carried out at weeks 0, 2, 4, 6, and 8. Side effects and subjects' satisfaction were also recorded. Cochran test was carried out to see the difference before and after treatment, with a p-value <0.05 considered significant. Majority of study subjects were 18-25 years (77.8%), had history of pregnancy (75%), had a history of menarche at the age of 12 years (27.8%) and all subjects had striae alba. There was significant decrement in INA score for striae distensae (p<0.001) after eight weeks administration of 3% green tea extract cream. Clinical improvement and no side effects were also noted. All subjects were satisfied. The use of 3% green tea extract cream can improve the appearance of SD.

An insular cortical circuit required for itch sensation and aversion

Itch encompasses both sensory and emotional dimensions, with the two dimensions reciprocally exacerbating each other. However, whether a shared neural circuit mechanism governs both dimensions remains elusive. Here, we report that the anterior insular cortex (AIC) is activated by both histamine-dependent and -independent itch stimuli. The activation of AIC elicits aversive emotion and exacerbates pruritogen-induced itch sensation and aversion. Mechanistically, AIC excitatory neurons project to the GABAergic neurons in the dorsal bed nucleus of the stria terminalis (dBNST). Manipulating the activity of the AIC → dBNST pathway affects both itch sensation and itch-induced aversion. Our study discovers the shared neural circuit (AIC→ dBNST pathway) underlying the itch sensation and aversion, highlights the critical role of the AIC as a central hub for the itch processing, and provides a framework to understand the neural mechanisms underlying the sensation and emotion interaction.

Spinal Nmur2-positive Neurons Play a Crucial Role in Mechanical Itch

The dorsal spinal cord is crucial for the transmission and modulation of multiple somatosensory modalities, such as itch, pain, and touch. Despite being essential for the well-being and survival of an individual, itch and pain, in their chronic forms, have increasingly been recognized as clinical problems. Although considerable progress has been made in our understanding of the neurochemical processing of nociceptive and chemical itch sensations, the neural substrate that is crucial for mechanical itch processing is still unclear. Here, using genetic and functional manipulation, we identified a population of spinal neurons expressing neuromedin U receptor 2 (Nmur2+) as critical elements for mechanical itch. We found that spinal Nmur2+ neurons are predominantly excitatory neurons, and are enriched in the superficial laminae of the dorsal horn. Pharmacogenetic activation of cervical spinal Nmur2+ neurons evoked scratching behavior. Conversely, the ablation of these neurons using a caspase-3-based method decreased von Frey filament-induced scratching behavior without affecting responses to other somatosensory modalities. Similarly, suppressing the excitability of cervical spinal Nmur2+ neurons via the overexpression of functional Kir2.1 potassium channels reduced scratching in response to innocuous mechanical stimuli, but not to pruritogen application. At the lumbar level, pharmacogenetic activation of these neurons evoked licking and lifting behaviors. However, ablating these neurons did not affect the behavior associated with acute pain. Thus, these results revealed the crucial role of spinal Nmur2+ neurons in mechanical itch. Our study provides important insights into the neural basis of mechanical itch, paving the way for developing novel therapies for chronic itch. PerspectiveExcitatory Nmur2+ neurons in the superficial dorsal spinal cord are essential for mechanical but not chemical itch information processing. These spinal Nmur2+ neurons represent a potential cellular target for future therapeutic interventions against chronic itch. Spinal and supraspinal Nmur2+ neurons may play different roles in pain signal processing.

Management of Vaipadika (Palmo Plantar Psoriasis) through Shodhana and Shamana- A Case Study

A localized form of Psoriasis known as Palmo plantar psoriasis is characterized by the development of thick, scaly and hyperkeratotic plaques. Despite the fact that this disease mostly affects the palms and soles, the hardness of the skin makes it difficult to do daily tasks. This condition is related to Vaipadika in Ayurveda. In the framework of Kshudra kusta, Vaipidika is explained. This illness is mostly caused by the Vatakapha dosha, which is identified by Pani pada sphuthana and Teerva vedhana. Here is a case of a 55 years old female with history of dryness ,scaling and cracks over her bilateral palms and soles associated with pain , blackish discoloration and severe itching and burning sensation, associated with bloody discharge since 1 year .Patient was treated with Snehana and Swedana and later Shamana oushadi were given for 7 days along with life style modification. Patient had good relief in symptoms.

ATF4 inhibits TRPV4 function and controls itch perception in rodents and nonhuman primates.

Acute and chronic itch are prevalent and incapacitating, yet the neural mechanisms underlying both acute and chronic itch are just starting to be unraveled. Activated transcription factor 4 (ATF4) belongs to the ATF/CREB transcription factor family and primarily participates in the regulation of gene transcription. Our previous study has demonstrated that ATF4 is expressed in sensory neurons. Nevertheless, the role of ATF4 in itch sensation remains poorly understood. Here, we demonstrate that ATF4 plays a significant role in regulating itch sensation. The absence of ATF4 in dorsal root ganglion (DRG) neurons enhances the itch sensitivity of mice. Overexpression of ATF4 in sensory neurons significantly alleviates the acute and chronic pruritus in mice. Furthermore, ATF4 interacts with the transient receptor potential cation channel subfamily V member 4 (TRPV4) and inhibits its function without altering the expression or membrane trafficking of TRPV4 in sensory neurons. In addition, interference with ATF4 increases the itch sensitivity in nonhuman primates and enhances TRPV4 currents in nonhuman primates DRG neurons; ATF4 and TRPV4 also co-expresses in human sensory neurons. Our data demonstrate that ATF4 controls pruritus by regulating TRPV4 signaling through a nontranscriptional mechanism and identifies a potential new strategy for the treatment of pathological pruritus.