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1.
Mol Brain ; 17(1): 27, 2024 May 23.
Article En | MEDLINE | ID: mdl-38783364

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.


Histamine , Mice, Inbred C57BL , Nucleus Accumbens , Pruritus , Animals , Pruritus/physiopathology , Pruritus/pathology , Male , Behavior, Animal , Proto-Oncogene Proteins c-fos/metabolism , Neurons/metabolism , Mice
2.
Int J Mol Sci ; 25(10)2024 May 09.
Article En | MEDLINE | ID: mdl-38791201

Chronic pruritus that lasts for over 6 weeks can present in various forms, like papules, nodules, and plaque types, with prurigo nodularis (PN) being the most prevalent. The pathogenesis of PN involves the dysregulation of immune cell-neural circuits and is associated with peripheral neuropathies, possibly due to chronic scratching. PN is a persistent and challenging condition, involving complex interactions among the skin, immune system, and nervous system. Lesional skin in PN exhibits the infiltration of diverse immune cells like T cells, eosinophils, macrophages, and mast cells, leading to the release of inflammatory cytokines and itch-inducing substances. Activated sensory nerve fibers aggravate pruritus by releasing neurotransmitters, perpetuating a vicious cycle of itching and scratching. Traditional treatments often fail, but recent advancements in understanding the inflammatory and itch transmission mechanisms of PN have paved the way for innovative therapeutic approaches, which are explored in this review.


Prurigo , Pruritus , Humans , Prurigo/etiology , Prurigo/therapy , Prurigo/pathology , Prurigo/drug therapy , Pruritus/etiology , Pruritus/therapy , Pruritus/pathology , Animals , Cytokines/metabolism , Skin/pathology , Skin/metabolism
3.
Sci Transl Med ; 16(746): eadk8198, 2024 May 08.
Article En | MEDLINE | ID: mdl-38718132

The phosphate modification of drugs is a common chemical strategy to increase solubility and allow for parenteral administration. Unfortunately, phosphate modifications often elicit treatment- or dose-limiting pruritus through an unknown mechanism. Using unbiased high-throughput drug screens, we identified the Mas-related G protein-coupled receptor X4 (MRGPRX4), a primate-specific, sensory neuron receptor previously implicated in itch, as a potential target for phosphate-modified compounds. Using both Gq-mediated calcium mobilization and G protein-independent GPCR assays, we found that phosphate-modified compounds potently activate MRGPRX4. Furthermore, a humanized mouse model expressing MRGPRX4 in sensory neurons exhibited robust phosphomonoester prodrug-evoked itch. To characterize and confirm this interaction, we further determined the structure of MRGPRX4 in complex with a phosphate-modified drug through single-particle cryo-electron microscopy (cryo-EM) and identified critical amino acid residues responsible for the binding of the phosphate group. Together, these findings explain how phosphorylated drugs can elicit treatment-limiting itch and identify MRGPRX4 as a potential therapeutic target to suppress itch and to guide future drug design.


Disease Models, Animal , Pruritus , Receptors, G-Protein-Coupled , Animals , Pruritus/metabolism , Pruritus/chemically induced , Pruritus/pathology , Pruritus/drug therapy , Humans , Receptors, G-Protein-Coupled/metabolism , Mice , HEK293 Cells , Phosphorylation/drug effects , Phosphates/metabolism , Sensory Receptor Cells/metabolism , Sensory Receptor Cells/drug effects , Prodrugs/pharmacology , Cryoelectron Microscopy
4.
Eur J Dermatol ; 34(1): 55-58, 2024 Feb 01.
Article En | MEDLINE | ID: mdl-38557459

Lichen striatus (LS), linear psoriasis (LPs), linear cutaneous lupus erythematosus (LCLE) and linear lichen planus (LLP) often have similar clinical manifestations, which makes clinical diagnosis with the naked eye difficult; therefore, they are easily misdiagnosed. The purpose of this study was to determine whether reflectance confocal microscopy (RCM) is helpful in differentiating between these four linear dermatoses in children. This retrospective study included 14 patients with LS, nine with LPs, eight with LCLE and 12 with LLP. All patients were analysed using RCM, and biopsies were collected from lesions previously imaged by RCM. For LS, the dermal papillary rings were partially absent, but when present, manifested with small, homogeneously round, bright cells and occasionally highly refractive plump cellular structures, aggregated in clusters. LPs exhibited dark cyst-like structures with small, bright, round cells aggregated at the epidermal level; at the dermal-epidermal junction, homogeneously distributed, enlarged, faint dermal papillary rings and numerous enlarged low-refractive canalicular structures were observed in the superficial dermis. LCLE and LLP exhibited similar manifestations, including epidermal disarray, almost total absence of dermal papillary rings, and various sized refractive structures densely distributed in the dermis. The key distinguishing features of LCLE were the different sized structures mainly clustered around hair follicles, while LLP demonstrated dense structures with a scattered distribution. RCM may be used to distinguish between the key features of LS, LPs, LCLE and LLP in children.


Keratosis , Lichen Planus , Psoriasis , Child , Humans , Retrospective Studies , Lipopolysaccharides , Epidermis/pathology , Lichen Planus/pathology , Keratosis/pathology , Psoriasis/pathology , Pruritus/pathology , Microscopy, Confocal/methods
5.
Mamm Genome ; 35(2): 122-134, 2024 Jun.
Article En | MEDLINE | ID: mdl-38523187

Pruritus is a common irritating sensation that provokes the desire to scratch. Environmental and genetic factors contribute to the onset of pruritus. Moreover, itch can become a major burden when it becomes chronic. Interestingly, the rare Collagen VI alpha 5 (COL6A5) gene variant p.Glu2272* has been identified in two families and an independent patient with chronic neuropathic itch. These patients showed reduced COL6A5 expression in skin and normal skin morphology. However, little progress has been made until now toward understanding the relationships between this mutation and chronic itch. Therefore, we developed the first mouse model that recapitulates COL6A5-p.Glu2272* mutation using the CRISPR-Cas technology and characterized this new mouse model. The mutant mRNA, measured by RT-ddPCR, was expressed at normal levels in dorsal root ganglia and was decreased in skin. The functional exploration showed effects of the mutation with some sex dysmorphology. Mutant mice had increased skin permeability. Elevated spontaneous scratching and grooming was detected in male and female mutants, with increased anxiety-like behavior in female mutants. These results suggest that the COL6A5-p.Glu2272* mutation found in patients contributes to chronic itch and induces in mice additional behavioral changes. The COL6A5-p.Glu2272* mouse model could elucidate the pathophysiological mechanisms underlying COL6A5 role in itch and help identify potential new therapeutic targets.


Collagen Type VI , Disease Models, Animal , Mutation , Pruritus , Animals , Mice , Pruritus/genetics , Pruritus/pathology , Female , Male , Collagen Type VI/genetics , Collagen Type VI/metabolism , Skin/pathology , Skin/metabolism , Chronic Disease , Humans , CRISPR-Cas Systems
7.
Genes (Basel) ; 15(2)2024 Jan 23.
Article En | MEDLINE | ID: mdl-38397136

Pruritus has long been linked to hepatic dysfunction; however, there are limited data characterizing the association between liver disease and prurigo nodularis (PN), a chronic inflammatory skin disease featuring severe pruritis. We thus conducted a cross-sectional analysis of hepatic comorbidities in PN patients using TriNetX, a large global health research network. This analysis revealed that PN patients had a higher risk (p < 0.001) of developing liver cirrhosis, acute and subacute hepatic failure, inflammatory liver disease, chronic hepatitis, nonalcoholic steatohepatitis, portal hypertension, fatty liver, chronic passive congestion of the liver, and hepatocellular carcinoma compared with healthy controls. The cumulative incidence of liver disease was about three times higher in PN patients compared with healthy controls. These findings provided the basis for translational studies to investigate a genetic mechanism for this association. Cutaneous transcriptomic analysis performed on PN patients revealed the dysregulation of genes related to hepatic failure in lesional PN compared with both nonlesional PN and control skin. Similarly, gene set variation analysis (GSVA) revealed a significantly increased (p < 0.05) activation of liver metabolism, chronic hepatic failure, acute hepatic failure, cholestatic liver disease, polycystic liver disease, and hepatocellular carcinoma pathways in lesional PN compared with control skin. A subsequent genome-wide association study (GWAS) identified shared single-nucleotide polymorphisms (SNPs) in the genes AR, EDIL3, MACROD2, PCSK5, RUNX1T1, TENM4, and ZEB2 between PN and liver disease from the FinnGen cohort. Significant dysregulation of the skin-liver axis in PN patients may explain the increased incidence and severity of hepatic comorbidities and help identify future therapeutic targets for PN.


Carcinoma, Hepatocellular , Liver Failure , Liver Neoplasms , Prurigo , Humans , Prurigo/genetics , Prurigo/drug therapy , Cross-Sectional Studies , Genome-Wide Association Study , Pruritus/drug therapy , Pruritus/etiology , Pruritus/pathology , Liver Neoplasms/genetics , Gene Expression Profiling , Genomics , Liver Failure/complications , Calcium-Binding Proteins , Cell Adhesion Molecules
8.
Eur Rev Med Pharmacol Sci ; 28(2): 571-576, 2024 Jan.
Article En | MEDLINE | ID: mdl-38305601

OBJECTIVE: This study aims to compare the effects of vaginal estrogen and hyaluronic acid on vulvovaginal atrophy. PATIENTS AND METHODS: This randomized controlled study included a total of 300 patients, with 150 patients in each group (Group E and Group H). The VHI score was determined based on a pre-treatment evaluation conducted by a gynecologist. After one month of receiving vaginal estrogen in Group E and vaginal hyaluronic acid in Group H, the patients were re-evaluated by their physicians. RESULTS: A statistically significant difference was found between the pre- and post-treatment VHI scores in Group E and Group H (p = 0.000; p = 0.000). No statistical difference was found between Group E and Group H in terms of treatment efficacy (p = 0.712). The pre- and post-treatment complaints of dryness, itching, dyspareunia, burning, and dysuria were found to be statistically significant in Group E and Group H (p = 0.000; p = 0.000; p = 0.000; p = 0.000; p = 0.000 in Group E, respectively) (p = 0.000; p = 0.000; p = 0.000; p = 0.000; p = 0.000 in Group H, respectively). No statistical difference was observed regarding dyspareunia, dysuria, and burning complaints (p = 0.632; p = 0.106; p = 0.128, respectively). However, hyaluronic acid was found to be significantly more effective for itching complaints (p = 0.002), while estrogen was found to be significantly more effective for dryness complaints (p = 0.012). CONCLUSIONS: Hyaluronic acid and estrogen were equally effective in vaginal treatment. Hyaluronic acid may be preferred for patients in whom hormonal therapy is contraindicated or for those who prefer non-hormonal therapy.


Dyspareunia , Hyaluronic Acid , Female , Humans , Estradiol/therapeutic use , Estradiol/pharmacology , Dyspareunia/pathology , Dysuria/chemically induced , Dysuria/pathology , Postmenopause , Vagina/pathology , Estrogens/therapeutic use , Estrogens/pharmacology , Treatment Outcome , Atrophy/drug therapy , Atrophy/pathology , Pruritus/pathology
9.
J Allergy Clin Immunol ; 153(1): 146-160, 2024 01.
Article En | MEDLINE | ID: mdl-37506977

BACKGROUND: Prurigo nodularis (PN) is a chronic neuroimmune skin disease characterized by bilaterally distributed pruritic hyperkeratotic nodules on extremities and trunk. Neuroimmune dysregulation and chronic scratching are believed to both induce and maintain the characteristic lesions. OBJECTIVES: This study sought to provide a comprehensive view of the molecular pathogenesis of PN at the single-cell level to identify and outline key pathologic processes and the cell types involved. Features that distinguish PN skin from the skin of patients with atopic dermatitis were of particular interest. We further aimed to determine the impact of the IL31RA antagonist, nemolizumab, and its specificity at the single-cell level. METHODS: Single-cell RNA-sequencing of skin from 15 healthy donors and nonlesional and lesional skin from 6 patients each with PN and atopic dermatitis, combined with spatial-sequencing using the 10x Visium platform. Integration with bulk RNA-sequencing data from patients treated with nemolizumab. RESULTS: This study demonstrates that PN is an inflammatory skin disease characterized by both keratinocyte proliferation and activation of profibrotic responses. This study also demonstrates that the COL11A1+ fibroblast subset is a major contributor to fibrosis and is predominantly found in the papillary dermis of PN skin. Activation of fibrotic responses is the main distinguishing feature between PN and atopic dermatitis skin. This study further shows the broad effect of nemolizumab on PN cell types, with a prominent effect driving COL11A1+ fibroblast and keratinocyte responses toward normal. CONCLUSIONS: This study provides a high-resolution characterization of the cell types and cellular processes activated in PN skin, establishing PN as a chronic fibrotic inflammatory skin disease. It further demonstrates the broad effect of nemolizumab on pathological processes in PN skin.


Dermatitis, Atopic , Prurigo , Humans , Prurigo/drug therapy , Dermatitis, Atopic/pathology , Skin/pathology , Chronic Disease , RNA , Pruritus/pathology
10.
J Allergy Clin Immunol ; 153(3): 852-859.e3, 2024 Mar.
Article En | MEDLINE | ID: mdl-37984799

BACKGROUND: Itch is a common symptom that can greatly diminish quality of life. Histamine is a potent endogenous pruritogen, and while antihistamines are often the first-line treatment for itch, in conditions like chronic spontaneous urticaria (CSU), many patients remain symptomatic while receiving maximal doses. Mechanisms that drive resistance to antihistamines are poorly defined. OBJECTIVES: Signaling of the alarmin cytokine IL-33 in sensory neurons is postulated to drive chronic itch by inducing neuronal sensitization to pruritogens. Thus, we sought to determine if IL-33 can augment histamine-induced (histaminergic) itch. METHODS: Itch behavior was assessed in response to histamine after IL-33 or saline administration. Various stimuli and conditional and global knockout mice were utilized to dissect cellular mechanisms. Multiple existing transcriptomic data sets were evaluated, including single-cell RNA sequencing of human and mouse skin, microarrays of isolated mouse mast cells at steady state and after stimulation with IL-33, and microarrays of skin biopsy samples from subjects with CSU and healthy controls. RESULTS: IL-33 amplifies histaminergic itch independent of IL-33 signaling in sensory neurons. Mast cells are the top expressors of the IL-33 receptor in both human and mouse skin. When stimulated by IL-33, mouse mast cells significantly increase IL-13 levels. Enhancement of histaminergic itch by IL-33 relies on a mast cell- and IL-13-dependent mechanism. IL-33 receptor expression is increased in lesional skin of subjects with CSU compared to healthy controls. CONCLUSIONS: Our findings suggest that IL-33 signaling may be a key driver of histaminergic itch in mast cell-associated pruritic conditions such as CSU.


Histamine , Skin , Mice , Animals , Humans , Skin/pathology , Histamine/metabolism , Interleukin-33/metabolism , Interleukin-13/genetics , Interleukin-13/metabolism , Quality of Life , Pruritus/pathology , Histamine Antagonists , Mice, Knockout
12.
JSLS ; 27(3)2023.
Article En | MEDLINE | ID: mdl-37663434

Objective: Determine the difference in microbial growth from the vagina and uterine manipulator among patients undergoing laparoscopic hysterectomy after randomization to one of three vaginal preparation solutions (10% Povidone-iodine, 2% Chlorhexidine, or 4% Chlorhexidine). Method: This was a prospective randomized controlled trial in an academic community hospital. Patients were ≥ 18 years old and scheduled for laparoscopic hysterectomy for benign and malignant indications. Results: Fifty patients were identified and randomized into each arm. Prior to surgery, the surgical team prepared the vaginal field using 10% Povidone-iodine, 2% Chlorhexidine, or 4% Chlorhexidine, according to group assignment. Cultures were collected from the vagina after initial preparation, prior to the colpotomy, and on surfaces of the uterine manipulator. Bacterial count from the baseline vaginal fornix/cervical canal cultures did not differ significantly among the three groups. There was a difference in bacterial count among the second cervical canal/vaginal fornix cultures (p < 0.01), with the Povidone-iodine arm demonstrating the highest level of growth of cultures (93.8%), followed by 2% Chlorhexidine (47.4%), and 4% Chlorhexidine (20%). There was no difference in growth on the uterine manipulator handle and no difference in vaginal itching or burning was found across the three arms postoperatively. Conclusion: Bacterial growth prior to colpotomy was the lowest with 4% Chlorhexidine followed by 2% Chlorhexidine, the Povidone-iodine group exhibited the highest bacterial growth. There was no difference in moderate to severe vaginal itching or burning. This showed that 4% Chlorhexidine is superior in reducing bacterial growth when used in laparoscopic hysterectomy.


Laparoscopy , Povidone-Iodine , Female , Humans , Adolescent , Chlorhexidine , Prospective Studies , Hysterectomy , Vagina/surgery , Pruritus/pathology , Pruritus/surgery , Hysterectomy, Vaginal
13.
J Allergy Clin Immunol ; 152(4): 927-932, 2023 10.
Article En | MEDLINE | ID: mdl-37453613

BACKGROUND: Therapies specifically targeting nonhistaminergic pruritus are largely lacking. Difelikefalin (DFK) has been found to reduce itch in various chronic pruritic conditions, including atopic dermatitis (AD). OBJECTIVE: We sought to investigate the ability of DFK to impact scratching behavior, inflammatory mediators, and neuronal signaling in a murine model of AD. METHODS: The ears of C57BL/6 mice were topically treated with MC903 for 12 consecutive days to induce AD-like inflammation and itch. Before MC903 treatment, mice were treated with either DFK (0.5 mg/kg, intraperitoneal injection twice daily) or vehicle (saline). Skin ear thickness, histological analysis, flow cytometry, RNA-sequencing, and differential gene expression analyses of mouse ear skin were used to examine the effect of DFK on skin inflammation. Scratching behavior was quantified to measure itch behavior in mice that were topically treated with MC903 for 6 consecutive days; then, mice received a single injection of either DFK (1.0 mg/kg, intraperitoneal injection) or saline. Calcium imaging and single-cell RNA-sequencing were used in mouse dorsal root ganglia neurons to determine the size of the neurons activated with DFK treatment. Statistical significance was determined by Mann-Whitney test, unless otherwise noted. RESULTS: DFK rapidly suppressed itch without altering AD-like skin inflammation in MC903 (calcipotriol)-treated mice. In vitro Ca2+ influx trace of dorsal root ganglia suggested that a major target for DFK is the larger-diameter mechanoreceptors (eg, Aꞵ-fibers), rather than small-diameter pruriceptive C-fibers. CONCLUSIONS: These studies support a potential neuromodulatory role of DFK for reducing itch associated with AD in mice.


Dermatitis, Atopic , Mice , Animals , Dermatitis, Atopic/pathology , Disease Models, Animal , Mice, Inbred C57BL , Pruritus/pathology , Skin/pathology , Inflammation/drug therapy , Inflammation/metabolism , RNA/metabolism
14.
Elife ; 122023 07 25.
Article En | MEDLINE | ID: mdl-37490401

Somatosensory information is processed by a complex network of interneurons in the spinal dorsal horn. It has been reported that inhibitory interneurons that express neuropeptide Y (NPY), either permanently or during development, suppress mechanical itch, with no effect on pain. Here, we investigate the role of interneurons that continue to express NPY (NPY-INs) in the adult mouse spinal cord. We find that chemogenetic activation of NPY-INs reduces behaviours associated with acute pain and pruritogen-evoked itch, whereas silencing them causes exaggerated itch responses that depend on cells expressing the gastrin-releasing peptide receptor. As predicted by our previous studies, silencing of another population of inhibitory interneurons (those expressing dynorphin) also increases itch, but to a lesser extent. Importantly, NPY-IN activation also reduces behavioural signs of inflammatory and neuropathic pain. These results demonstrate that NPY-INs gate pain and itch transmission at the spinal level, and therefore represent a potential treatment target for pathological pain and itch.


Neuralgia , Neuropeptide Y , Mice , Animals , Neuropeptide Y/genetics , Spinal Cord Dorsal Horn/pathology , Pruritus/pathology , Interneurons/physiology , Spinal Cord/physiology
15.
J Eur Acad Dermatol Venereol ; 37(11): 2336-2348, 2023 Nov.
Article En | MEDLINE | ID: mdl-37326015

BACKGROUND: Atopic dermatitis (AD) is a chronic and recurrent inflammatory skin disease characterized by severe pruritus and eczematous lesions. Heterogeneity of AD has been reported among different racial groups according to clinical, molecular and genetic differences. OBJECTIVE: This study aimed to conduct an in-depth transcriptome analysis of AD in Chinese population. METHODS: We performed single-cell RNA sequencing (scRNA-seq) analysis of skin biopsies from five Chinese adult patients with chronic AD and from four healthy controls, combined with multiplexed immunohistochemical analysis in whole-tissue skin biopsies. We explored the functions of IL19 in vitro. RESULTS: ScRNA-seq analysis was able to profile a total of 87,853 cells, with keratinocytes (KCs) in AD manifesting highly expressed keratinocyte activation and pro-inflammatory genes. KCs demonstrated a novel IL19+ IGFL1+ subpopulation that increased in AD lesions. Inflammatory cytokines IFNG, IL13, IL26 and IL22 were highly expressed in AD lesions. In vitro, IL19 directly downregulated KRT10 and LOR in HaCaT cells and activated HaCaT cells to produce TSLP. CONCLUSION: Abnormal proliferation and differentiation of keratinocytes contribute immensely to the pathogenesis of AD, whereas AD chronic lesions have witnessed significant presence of IL19+ IGFL1+ KCs, which may be involved in the disruption of the skin barrier, the connection and magnification of Th2 and Th17 inflammatory responses, and mediation of skin pruritus. Furthermore, progressive activation of multiple immune axes dominated by Type 2 inflammatory reaction occur in AD chronic lesions.


Dermatitis, Atopic , Adult , Humans , Dermatitis, Atopic/pathology , Single-Cell Gene Expression Analysis , Keratinocytes/pathology , Skin/pathology , Cytokines , Cell Differentiation , Pruritus/pathology
16.
Am J Manag Care ; 29(5 Suppl): S63-S72, 2023 05.
Article En | MEDLINE | ID: mdl-37146288

Prurigo nodularis (PN) is a chronic neural- and immune-mediated disease that is characterized by intense itch, history of skin scratching, and development of papulonodular lesions. These lesions can develop consequent to a cycle of itching and scratching associated with inflammation and changes in skin cells and nerve fibers (eg, pathogenic skin fibrosis, tissue remodeling, and chronic neuronal sensitization). Diagnosis of PN involves individual evaluation of clinical characteristics to identify disease and symptom severity. In the United States, adult patients with PN (estimated, < 90,000) are more likely to be older (age, 50-60 years); in addition, this disease is detected at higher rates in women and Black individuals relative to other demographic subgroups. Still, the small population of patients with PN exhibits considerably high use of health care resources and experiences considerable symptom burden and negatively impacted quality of life. Further, PN is associated with increased rates of a range of comorbid diseases compared with other inflammatory dermatoses (eg, atopic dermatitis, psoriasis). Adequate treatment must address both the neural and immunological component of the disease; there remains a great unmet need for safe and effective therapies that can reduce the burden of disease.


Dermatitis, Atopic , Prurigo , Adult , Humans , Female , United States/epidemiology , Middle Aged , Prurigo/epidemiology , Prurigo/therapy , Prurigo/diagnosis , Quality of Life , Pruritus/epidemiology , Pruritus/etiology , Pruritus/pathology , Skin
17.
Int J Mol Sci ; 24(7)2023 Mar 28.
Article En | MEDLINE | ID: mdl-37047310

(1) Inverse psoriasis (IP), also known as intertriginous, typically affects the groin, armpits, navel, intergluteal fissure, and external genitalia. Skin lesions are erythematous plaques of inflammatory nature, smooth, well-delimited, non-scaly, and non-infiltrated. Lesions may be accompanied by itching, pain, or burning sensation. The aim of this study is both to investigate the modulation of the skin microbiota induced by IP and, on the other hand, to test the effectiveness of the new biotechnological product LimpiAL 2.5%. (2) Patients affected by IP were recruited in a private practice and treated for 4 weeks with LimpiAL 2.5% exclusively. The clinical effects on the lesion skin were evaluated, and the skin microbiotas before and after treatment were compared. (3) The clinical outcomes reveled a significant beneficial effect of the tested product. At the same time, LimpiAL increased the biological diversity of the skin microbiota and exerted a significant decrease of some Corynebacterium species, and the increase of some Staphylococcus species. (4) Together, the clinical outcomes and the microbiota analysis suggest that LimpiAL treatment improves the skin condition of affected patients, basically restoring the eubiosis conditions of the affected sites and modulating the bacterial composition of the resident microbiota.


Microbiota , Psoriasis , Humans , Psoriasis/drug therapy , Skin/pathology , Erythema/pathology , Pruritus/pathology
18.
Sensors (Basel) ; 23(8)2023 Apr 12.
Article En | MEDLINE | ID: mdl-37112275

Atopic dermatitis (AD) is one of the most common skin disorders, affecting nearly one-fifth of children and adolescents worldwide, and currently, the only method of monitoring the condition is through an in-person visual examination by a clinician. This method of assessment poses an inherent risk of subjectivity and can be restrictive to patients who do not have access to or cannot visit hospitals. Advances in digital sensing technologies can serve as a foundation for the development of a new generation of e-health devices that provide accurate and empirical evaluation of the condition to patients worldwide. The goal of this review is to study the past, present, and future of AD monitoring. First, current medical practices such as biopsy, tape stripping and blood serum are discussed with their merits and demerits. Then, alternative digital methods of medical evaluation are highlighted with the focus on non-invasive monitoring using biomarkers of AD-TEWL, skin permittivity, elasticity, and pruritus. Finally, possible future technologies are showcased such as radio frequency reflectometry and optical spectroscopy along with a short discussion to provoke research into improving the current techniques and employing the new ones to develop an AD monitoring device, which could eventually facilitate medical diagnosis.


Dermatitis, Atopic , Child , Adolescent , Humans , Dermatitis, Atopic/diagnosis , Water Loss, Insensible , Skin/pathology , Pruritus/pathology , Biomarkers
19.
Eur J Obstet Gynecol Reprod Biol ; 285: 41-45, 2023 Jun.
Article En | MEDLINE | ID: mdl-37044017

BACKGROUND AND OBJECTIVE: Vaginal atrophy is a condition where the vaginal epithelium gets thinner and includes symptoms, such as vaginal dryness, abnormal vaginal discharge, vaginal bleeding, dyspareunia, and sexual problems. Hormone therapy is associated with some problems and some women prefer herbal medicine to reduce vaginal atrophy. Considering the phytoestrogenic compounds present in the nettle, this study aimed to investigate the effect of the nettle vaginal cream on subjective symptoms of vaginal atrophy in postmenopausal women. MATERIALS AND METHODS: This triple-blind randomized placebo-controlled clinical trial study was conducted on 84 eligible postmenopausal women aged 45-60 years, who referred to comprehensive health service centers in Aliabad Katul in 2021-2022. Women eligible for the study received 5% nettle vaginal cream and placebo for 8 weeks. Subjective symptoms of vaginal atrophy were assessed before, four and eight weeks after the intervention. Data collection tools included a checklist for research unit selection, individual and midwifery characteristics questionnaire, vaginal assessment scale (VAS), vaginal pH, laboratory results of the vaginal maturation value (VMV). Data analysis was performed using SPSS software (version 21) and independent t-test, Mann-Whitney, chi-square, Two-way analysis of variance and analysis of covariance. P value less than 0.05 was considered significant. RESULTS: Subjective symptoms of vaginal atrophy decreased significantly after the intervention compared to before the intervention in both the nettle and placebo groups (p < 0.001), but in the comparison between groups four weeks and eight weeks after the intervention, the subjective symptoms of vaginal atrophy in nettle group decreased significantly (p < 0.001). In the nettle group, the scores of vaginal burning, vaginal dryness, vaginal itching and dyspareunia significantly improved after the intervention compared to before the intervention (p < 0.001). Also, in the nettle group compared to the placebo group, after the intervention, vaginal burning and vaginal dryness score (p < 0.001) and vaginal itching score (0.004) improved significantly. CONCLUSION: Based on the results of the present study, Nettle vaginal cream reduced subjective symptoms of vaginal atrophy, including vaginal burning, vaginal dryness, vaginal itching, and dyspareunia in postmenopausal women, so it is a cost-effective, available and do not have the side effects product that can be useful for menopausal women.


Dyspareunia , Vaginal Diseases , Female , Humans , Vaginal Creams, Foams, and Jellies/therapeutic use , Postmenopause , Dyspareunia/drug therapy , Administration, Intravaginal , Vaginal Diseases/drug therapy , Vaginal Diseases/pathology , Vagina , Atrophy/drug therapy , Atrophy/pathology , Pruritus/drug therapy , Pruritus/pathology , Treatment Outcome
20.
Inflamm Res ; 72(5): 933-945, 2023 May.
Article En | MEDLINE | ID: mdl-36997814

BACKGROUND: Curcumin is a diketone compound extracted from the rhizomes of some plants in the Zingiberaceae and Araceae family. It possesses a variety of biological activities, including antioxidant, anti-inflammatory and anti-cancer properties. However, the cellular and molecular antipruritic mechanisms of curcumin remain to be explored. OBJECTIVE: Our objective was to study the role of curcumin in pruritus and determine whether its antipruritic effect is related to MrgprB2 receptor. METHODS: The effect of curcumin on pruritus in mice was examined by scratching behavior test. The antipruritic mechanism of curcumin was explored by using transgenic mice (MrgprB2-/- mice, MrgprB2CreTd/tomato mice), histological analysis, western blot and immunofluorescence. In addition, the relationship between curcumin and MrgprB2/X2 receptor was studied in vitro by using calcium imaging, plasmid transfection and molecular docking RESULTS: In the current study, we found that curcumin had obvious antipruritic effect. Its antipruritic effect was related to the regulation of MrgprB2 receptor activation and mast cells tryptase release. In vitro, mouse peritoneal mast cells activated by compound 48/80 could be inhibited by curcumin. In addition, curcumin was also found to suppress the calcium flux in MrgprX2 or MrgprB2-overexpression HEK cells induced by compound 48/80, substance P, and PAMP 9-20, displaying the specific relation with the MrgprB2/X2 receptor. Moreover, molecular docking results showed that curcumin had affinity to MrgprX2 protein. CONCLUSIONS: Overall, these results indicated that curcumin has the potential to treat pruritus induced by mast cell MrgprB2 receptor.


Curcumin , Mast Cells , Mice , Animals , Curcumin/pharmacology , Curcumin/therapeutic use , Calcium/metabolism , Antipruritics/metabolism , Antipruritics/pharmacology , Molecular Docking Simulation , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism , Pruritus/drug therapy , Pruritus/metabolism , Pruritus/pathology , Cell Degranulation , Mice, Inbred C57BL
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