Background:While mild itching may seem harmless,it can worsen over time,necessitating early treatment.Epicutaneous sensitization has recently gained attention.Oral exposure may promote immune tolerance,but ingestion a...Background:While mild itching may seem harmless,it can worsen over time,necessitating early treatment.Epicutaneous sensitization has recently gained attention.Oral exposure may promote immune tolerance,but ingestion after epicutaneous sensitization can trigger severe allergic responses.Therefore,this study focused on the initial stages of allergic symptoms before they become severe and investigated the mechanisms underlying food ingestion-induced mild itching following epicutaneous sensitization.Methods:Female mice were epicutaneously sensitized with ovalbumin(OVA).Scratching behavior was recorded,and serum and tissue samples were collected.Levels of OVA-specific immunoglobulin(Ig)E/IgG1,histamine,and mast cell protease-1(MCPT-1)were measured by ELISA.Histological analysis of skin tissues and immune cell infiltration was performed via staining.Results:OVA challenge following epicutaneous sensitization induced mild itching in the OVA group.Scratching behavior peaked between 1 and 2 h and persisted for 8 h before returning to baseline.This itching was accompanied by dynamic fluctuations in OVA-specific IgE and IgG1,histamine,and MCPT-1 levels.Histological analysis revealed increased epidermal thickness and granulocytic infiltration,particularly of mast cells and eosinophils,within 2 h of OVA challenge.Mast cell and eosinophil migration into the skin tissues was significant,with eosinophil migration into the dermis persisted despite normalization of histamine levels and mast cell degranulation.These results suggest that mast cells and eosinophils play significant roles even in mild itching.Conclusion:This study provides insights into the early immune responses involved in food allergies,contributing to a better understanding of how mild symptoms can progress to more severe reactions.展开更多
Objective To observe the clinical efficacy of ＂itching symptom＂ of allergic rhinitis treated from the perspective of ＂wind＂. Methods Forty patients were given acupuncture therapy, Fengchf （风池 GB 20, bilaterally...Objective To observe the clinical efficacy of ＂itching symptom＂ of allergic rhinitis treated from the perspective of ＂wind＂. Methods Forty patients were given acupuncture therapy, Fengchf （风池 GB 20, bilaterally）, Dazhui （大椎 GV 14）, Fengmen （风门 BL 12, bilaterally）, Feishu （肺俞 BL 13, bilaterally） and Shangyingxiang （上迎香 EX-HN8, bilaterally） were selected. After needle withdrawal, a fire cup was applied between GV 14 and BL 13, and the cup was retained for 10 min. Treatment for 15 times was considered as 1 course of treatment. Three days were free from treatment between 2 courses, and 3 courses were needed. The curative effect was evaluated after treatment ends, and follow-up visit was performed one year after treatment. Results The scores of nasal symptom and itching symptom after treatment ends and one year after treatment significantly reduced when compared with that before treatment （all P〈0.05）, the difference was not statistically significant when compared the scores of nasal symptom and itching symptom one year after treatment with that after treatment ends （both P〉O.O5）.According to the follow-up visit performed one year after treatment, the markedly effective and effective cases reduced, ineffective cases increased, and the total effective rate declined slightly. The serum IgE levels, after treatment ends I-（164.79±44.29） IU/mL and one year after treatment [（180.71±52.81）IU/ mL] , both significantly reduced when compared with that before treatment [（380.12±61.45） IU/mL, both P〈0.05] , the serum igE level one year after treatment increased when compared with that after treatment ends, but the difference was not statistically significant （P〉O.05）. Conclusion （1） Significant short-term and long-term curative effects have been obtained during the treatment of ＂itching symptom＂ of allergic rhinitis from the perspective of ＂wind＂, （2） the mechanism of action may be related with the decrease of serum IgE level, （3） it is indicated that there are correlations between allergic rhinitis and atopic diseases such as atopic dermatitis and allergic conjunctivitis, etc.展开更多
The averaging in optimal switching control problems is considered under the following two cases:the switching cost does not depend onεand the switching cost vanishes asεtends to zero.The value function of the or...The averaging in optimal switching control problems is considered under the following two cases:the switching cost does not depend onεand the switching cost vanishes asεtends to zero.The value function of the original fast problem converges locally uniformly to the value function of the averaged problem under both cases.The ways of averaging turn out to be different between both cases.展开更多
In 2012,we published the first special issue on the mechanisms of pain and itch in Neuroscience Bulletin[1],covering peripheral[2,3],central[4],and glial[5]mechanisms.In 2018,the second special issue expanded on these...In 2012,we published the first special issue on the mechanisms of pain and itch in Neuroscience Bulletin[1],covering peripheral[2,3],central[4],and glial[5]mechanisms.In 2018,the second special issue expanded on these topics[6],featuring single-cell profiling and in vivo Ca2+imaging of primary sensory neurons[7,8],and illustrating how nociceptors regulate pain,itch,and infection[9].It also highlighted spinal neurocircuits of pain[10]and itch[11],glial contributions[12],sex differences[13],and supraspinal mechanisms underlying pain and empathy[14,15].Over the past seven years,significant advances have been made in neuroglial and neuroimmune interactions and supraspinal circuits.Thus,this third special issue—comprising one review,eleven original articles,and one research highlight[16,17,18,19,20,21,22,23,24,25,26,27,28]—timely summarizes recent progress in pain and itch research.展开更多
Neuraxial opioids,widely used in obstetric and perioperative pain management,often lead to unwanted itch,reducing patient satisfaction.While theμ-opioid receptor has been implicated in opioid-induced itch,the genetic...Neuraxial opioids,widely used in obstetric and perioperative pain management,often lead to unwanted itch,reducing patient satisfaction.While theμ-opioid receptor has been implicated in opioid-induced itch,the genetic basis for variable itch incidence remains unknown.This study examined 3616 patients receiving epidural opioids,revealing an itch occurrence of 26.55%,with variations among opioid types and gender.Analysis of the OPRM1 gene identified six single-nucleotide polymorphisms,notably rs1799971(A118G),that correlated with opioid-induced itch.Mouse models with an equivalent A112G mutation showed reduced neuraxial opioid-induced itch and light touch-evoked itch,mirroring human findings.The 118G allele demonstrated an anti-itch effect without impacting analgesia,addiction,or tolerance,offering insights for risk stratification and potential anti-itch pretreatment strategies.展开更多
The anterior cingulate cortex(ACC)has recently been proposed as a key player in the representation of itch stimuli.However,to date,little is known about the contribution of specific ACC interneuron populations to itch...The anterior cingulate cortex(ACC)has recently been proposed as a key player in the representation of itch stimuli.However,to date,little is known about the contribution of specific ACC interneuron populations to itch processing.Using c-Fos immunolabeling and in vivo Ca2+imaging,we reported that both histamine and chloroquine stimuli-induced acute itch caused a marked enhancement of vasoactive intestinal peptide(VIP)-expressing interneuron activity in the ACC.Behavioral data indicated that optogenetic and chemogenetic activation of these neurons reduced scratching responses related to histaminergic and non-histaminergic acute itch.Similar neural activity and modulatory role of these neurons were seen in mice with chronic itch induced by contact dermatitis.Together,this study highlights the importance of ACC VIP+neurons in modulating itch-related affect and behavior,which may help us to develop novel mechanism-based strategies to treat refractory chronic itch in the clinic.展开更多
Objective:To investigate the activity of the active principle in the spines of the seed pods of Mucuna pruriens using contraction of guinea pig ileum as index of pharmacological activity. Methods:The active principle ...Objective:To investigate the activity of the active principle in the spines of the seed pods of Mucuna pruriens using contraction of guinea pig ileum as index of pharmacological activity. Methods:The active principle was extracted with 0.0015 M NaCl.Muscle strips of guinea pig ileum were prepared and contractile responses were measured using a Kymograph.Two sets of experiment were conducted:（1）.The contraction of the ileum in presence of different concentrations of histamine,2-methylhistamine and the extract of Mucuna pruriens.（2）.The contractile response of the ileum in presence of different concentrations of the extract and antagonists including diphenhydramine,atropine and methysergide.Results:（1） The extract of Mucuna pruriens hair, 2- methylhistamine and histamine produced dose dependent contraction of guinea pig ileum (Extract ED<sub>50</sub> = 13.0μg/mL,2-methylhistamine ED<sub>50</sub>=8.5μg/mL and histamine ED<sub>50</sub>=10.0μg/ mL).（2） Diphenhydramine,an H,antagonist competitively blocked the contractile response of the Mucuna pruriens extract（3） Coadminstration of the Mucuna pruriens extract either with different doses of antimuscarinic agent atropine or 5-hydroxytryptamine blocking agent methysergide did not alter the extract induced contractile response of the guinea pig ileum.Conclusion:These results demonstrate that the spines of Mucuna pruriens possess histamine activity which may contribute to its itching and painful irritation effects.展开更多
Background: Pruritus is a distressing symptom of cholestatic, inflammatory, and malignant liver diseases. It is a common symptom in many biliary and cholestatic disorders such as primary biliary cirrhosis (PBC). Sever...Background: Pruritus is a distressing symptom of cholestatic, inflammatory, and malignant liver diseases. It is a common symptom in many biliary and cholestatic disorders such as primary biliary cirrhosis (PBC). Several mechanisms are generally accepted as possible explanations to the underlying basis of itch. However, the exact pathophysiology of pruritus in liver diseases remains unclear. The cutaneous and central neurobiology of pruritus is complex and underlies a regulation of variable mechanisms. At present, not all mechanisms including neuromediators and receptors are known. Objective: Our objective is to evaluate whether the expression pattern of NGF and its receptor TrK A has a role in pruritus in a group of Egyptian cirrhotic patients. Patients and Methods: Forty Patients with liver cirrhosis were enrolled in the study depending on clinical evidence of stigmata of chronic liver disease (e.g. jaundice, ascites, palmar erythema, spider naevi, etc.) and ultrasonographic features of liver cirrhosis (e.g. coarse echo texture, shrunken liver, etc.). Patients were divided into two groups. Group (1): included 20 patients cirrhotic patients without pruritus. Group (2): included 20 patients cirrhotic patients with pruritus. A group of age and sex matched healthy twenty volunteers as a control. Results: After evaluation of histopathological using hematoxylin and eosin stained sections (H&E) was done. There was positive correlation between NGF protein expression and severity of pruritus in cirrhotic patients with pruritus (r = 0.876, p value ≤ 0.001). Also there was positive correlation between TrK A protein expression and severity of pruritus in cirrhotic patients with pruritus (r = 0.44, p value ≤ 0.05). Conclusions: We report, for the first time, role of these proteins (NGF/TrK A) in the mechanism of pruritus in cirrhotic patients and may provide a potential target for new treatment of pruritus in cirrhotic.展开更多
[Objectives]To observe and analyze the clinical efficacy and possible mechanism of Chuanbai antipruritic lotion"water film"wet compress combined with chloramphenicol prednisone liniment in the treatment of a...[Objectives]To observe and analyze the clinical efficacy and possible mechanism of Chuanbai antipruritic lotion"water film"wet compress combined with chloramphenicol prednisone liniment in the treatment of acute eczema.[Methods]A total of 76 acute eczema cases admitted to Shiyan Taihe Hospital from January 2022 to March 2023 were divided into Western medicine treatment group and integrated traditional Chinese and Western medicine group.In the Western medicine treatment group,chloramphenicol and prednisone liniment was applied to the skin lesions and oral administration of cetirizine hydrochloride.The course of treatment in both groups was 2 weeks(w).The levels of interferon-γ(IFN-γ),interleukin-4(IL-4)and the ratio of IFN-γ/IL-4 in the peripheral blood of patients before and 2 weeks after treatment,as well as serum immunoglobulin E(IgE),anti-IgE antibody and histamine(HA)level,and with skin lesions disappearing time,skin oil,transepidermal water loss(TEWL),eczema area and severity index(EASI)score,total effective rate,degree of pruritus and traditional Chinese medicine quality of life scale(EPQOLS)score to evaluate the efficacy.[Results]Compared with the Western medicine treatment group at 2 w,the disappearance time of skin lesions in the integrated traditional Chinese and Western medicine group was shortened,TEWL,itching degree and EASI score,serum IgE and HA,and peripheral blood IL-4 levels were all decreased(P<0.05).IFN-γand IFN-γ/IL-4 ratio,anti-IgE antibody,EPQOLS score and total effective rate were all increased(P<0.05),and the difference was statistically significant.[Conclusions]Chuanbai antipruritic lotion"water film"wet compress combined with chloramphenicol prednisone liniment is an optimized and safe and efficient method for the treatment of acute eczema,which can quickly relieve the symptoms of inflammatory damage of eczema and restore the skin barrier function,dry dampness and relieve itch.Inhibition of the release of histamine active substances and regulation of immunity may be the main mechanisms.展开更多
基金supported by JSPS KAKENHI Grant Number(22K11779).
文摘Background:While mild itching may seem harmless,it can worsen over time,necessitating early treatment.Epicutaneous sensitization has recently gained attention.Oral exposure may promote immune tolerance,but ingestion after epicutaneous sensitization can trigger severe allergic responses.Therefore,this study focused on the initial stages of allergic symptoms before they become severe and investigated the mechanisms underlying food ingestion-induced mild itching following epicutaneous sensitization.Methods:Female mice were epicutaneously sensitized with ovalbumin(OVA).Scratching behavior was recorded,and serum and tissue samples were collected.Levels of OVA-specific immunoglobulin(Ig)E/IgG1,histamine,and mast cell protease-1(MCPT-1)were measured by ELISA.Histological analysis of skin tissues and immune cell infiltration was performed via staining.Results:OVA challenge following epicutaneous sensitization induced mild itching in the OVA group.Scratching behavior peaked between 1 and 2 h and persisted for 8 h before returning to baseline.This itching was accompanied by dynamic fluctuations in OVA-specific IgE and IgG1,histamine,and MCPT-1 levels.Histological analysis revealed increased epidermal thickness and granulocytic infiltration,particularly of mast cells and eosinophils,within 2 h of OVA challenge.Mast cell and eosinophil migration into the skin tissues was significant,with eosinophil migration into the dermis persisted despite normalization of histamine levels and mast cell degranulation.These results suggest that mast cells and eosinophils play significant roles even in mild itching.Conclusion:This study provides insights into the early immune responses involved in food allergies,contributing to a better understanding of how mild symptoms can progress to more severe reactions.
文摘Objective To observe the clinical efficacy of ＂itching symptom＂ of allergic rhinitis treated from the perspective of ＂wind＂. Methods Forty patients were given acupuncture therapy, Fengchf （风池 GB 20, bilaterally）, Dazhui （大椎 GV 14）, Fengmen （风门 BL 12, bilaterally）, Feishu （肺俞 BL 13, bilaterally） and Shangyingxiang （上迎香 EX-HN8, bilaterally） were selected. After needle withdrawal, a fire cup was applied between GV 14 and BL 13, and the cup was retained for 10 min. Treatment for 15 times was considered as 1 course of treatment. Three days were free from treatment between 2 courses, and 3 courses were needed. The curative effect was evaluated after treatment ends, and follow-up visit was performed one year after treatment. Results The scores of nasal symptom and itching symptom after treatment ends and one year after treatment significantly reduced when compared with that before treatment （all P〈0.05）, the difference was not statistically significant when compared the scores of nasal symptom and itching symptom one year after treatment with that after treatment ends （both P〉O.O5）.According to the follow-up visit performed one year after treatment, the markedly effective and effective cases reduced, ineffective cases increased, and the total effective rate declined slightly. The serum IgE levels, after treatment ends I-（164.79±44.29） IU/mL and one year after treatment [（180.71±52.81）IU/ mL] , both significantly reduced when compared with that before treatment [（380.12±61.45） IU/mL, both P〈0.05] , the serum igE level one year after treatment increased when compared with that after treatment ends, but the difference was not statistically significant （P〉O.05）. Conclusion （1） Significant short-term and long-term curative effects have been obtained during the treatment of ＂itching symptom＂ of allergic rhinitis from the perspective of ＂wind＂, （2） the mechanism of action may be related with the decrease of serum IgE level, （3） it is indicated that there are correlations between allergic rhinitis and atopic diseases such as atopic dermatitis and allergic conjunctivitis, etc.
基金supported by the National Natural Science Foundation of China.
文摘The averaging in optimal switching control problems is considered under the following two cases:the switching cost does not depend onεand the switching cost vanishes asεtends to zero.The value function of the original fast problem converges locally uniformly to the value function of the averaged problem under both cases.The ways of averaging turn out to be different between both cases.
文摘In 2012,we published the first special issue on the mechanisms of pain and itch in Neuroscience Bulletin[1],covering peripheral[2,3],central[4],and glial[5]mechanisms.In 2018,the second special issue expanded on these topics[6],featuring single-cell profiling and in vivo Ca2+imaging of primary sensory neurons[7,8],and illustrating how nociceptors regulate pain,itch,and infection[9].It also highlighted spinal neurocircuits of pain[10]and itch[11],glial contributions[12],sex differences[13],and supraspinal mechanisms underlying pain and empathy[14,15].Over the past seven years,significant advances have been made in neuroglial and neuroimmune interactions and supraspinal circuits.Thus,this third special issue—comprising one review,eleven original articles,and one research highlight[16,17,18,19,20,21,22,23,24,25,26,27,28]—timely summarizes recent progress in pain and itch research.
基金supported by the National Natural Science Foundation of China(32271047)the National Key Research and Development Program of China(2020YFC2008405)+1 种基金The Innovative Research Team of High-level Local Universities in Shanghai,the Natural Science Foundation of Shanghai(22ZR1413800)Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)。
文摘Neuraxial opioids,widely used in obstetric and perioperative pain management,often lead to unwanted itch,reducing patient satisfaction.While theμ-opioid receptor has been implicated in opioid-induced itch,the genetic basis for variable itch incidence remains unknown.This study examined 3616 patients receiving epidural opioids,revealing an itch occurrence of 26.55%,with variations among opioid types and gender.Analysis of the OPRM1 gene identified six single-nucleotide polymorphisms,notably rs1799971(A118G),that correlated with opioid-induced itch.Mouse models with an equivalent A112G mutation showed reduced neuraxial opioid-induced itch and light touch-evoked itch,mirroring human findings.The 118G allele demonstrated an anti-itch effect without impacting analgesia,addiction,or tolerance,offering insights for risk stratification and potential anti-itch pretreatment strategies.
基金supported by grants from the National Natural Science Foundation of China(82271243 and 82101318)Shaanxi Province Key Research and Development Plan(2024SF-ZDCYL-01-13)+1 种基金the support funding from Fourth Military Medical University(2024JC005,2020AXJHHJ,and XJZT24JC27)Liaoning Provincial Joint Science and Technology Program(2023-MSLH-345).
文摘The anterior cingulate cortex(ACC)has recently been proposed as a key player in the representation of itch stimuli.However,to date,little is known about the contribution of specific ACC interneuron populations to itch processing.Using c-Fos immunolabeling and in vivo Ca2+imaging,we reported that both histamine and chloroquine stimuli-induced acute itch caused a marked enhancement of vasoactive intestinal peptide(VIP)-expressing interneuron activity in the ACC.Behavioral data indicated that optogenetic and chemogenetic activation of these neurons reduced scratching responses related to histaminergic and non-histaminergic acute itch.Similar neural activity and modulatory role of these neurons were seen in mice with chronic itch induced by contact dermatitis.Together,this study highlights the importance of ACC VIP+neurons in modulating itch-related affect and behavior,which may help us to develop novel mechanism-based strategies to treat refractory chronic itch in the clinic.
文摘Objective:To investigate the activity of the active principle in the spines of the seed pods of Mucuna pruriens using contraction of guinea pig ileum as index of pharmacological activity. Methods:The active principle was extracted with 0.0015 M NaCl.Muscle strips of guinea pig ileum were prepared and contractile responses were measured using a Kymograph.Two sets of experiment were conducted:（1）.The contraction of the ileum in presence of different concentrations of histamine,2-methylhistamine and the extract of Mucuna pruriens.（2）.The contractile response of the ileum in presence of different concentrations of the extract and antagonists including diphenhydramine,atropine and methysergide.Results:（1） The extract of Mucuna pruriens hair, 2- methylhistamine and histamine produced dose dependent contraction of guinea pig ileum (Extract ED<sub>50</sub> = 13.0μg/mL,2-methylhistamine ED<sub>50</sub>=8.5μg/mL and histamine ED<sub>50</sub>=10.0μg/ mL).（2） Diphenhydramine,an H,antagonist competitively blocked the contractile response of the Mucuna pruriens extract（3） Coadminstration of the Mucuna pruriens extract either with different doses of antimuscarinic agent atropine or 5-hydroxytryptamine blocking agent methysergide did not alter the extract induced contractile response of the guinea pig ileum.Conclusion:These results demonstrate that the spines of Mucuna pruriens possess histamine activity which may contribute to its itching and painful irritation effects.
文摘Background: Pruritus is a distressing symptom of cholestatic, inflammatory, and malignant liver diseases. It is a common symptom in many biliary and cholestatic disorders such as primary biliary cirrhosis (PBC). Several mechanisms are generally accepted as possible explanations to the underlying basis of itch. However, the exact pathophysiology of pruritus in liver diseases remains unclear. The cutaneous and central neurobiology of pruritus is complex and underlies a regulation of variable mechanisms. At present, not all mechanisms including neuromediators and receptors are known. Objective: Our objective is to evaluate whether the expression pattern of NGF and its receptor TrK A has a role in pruritus in a group of Egyptian cirrhotic patients. Patients and Methods: Forty Patients with liver cirrhosis were enrolled in the study depending on clinical evidence of stigmata of chronic liver disease (e.g. jaundice, ascites, palmar erythema, spider naevi, etc.) and ultrasonographic features of liver cirrhosis (e.g. coarse echo texture, shrunken liver, etc.). Patients were divided into two groups. Group (1): included 20 patients cirrhotic patients without pruritus. Group (2): included 20 patients cirrhotic patients with pruritus. A group of age and sex matched healthy twenty volunteers as a control. Results: After evaluation of histopathological using hematoxylin and eosin stained sections (H&E) was done. There was positive correlation between NGF protein expression and severity of pruritus in cirrhotic patients with pruritus (r = 0.876, p value ≤ 0.001). Also there was positive correlation between TrK A protein expression and severity of pruritus in cirrhotic patients with pruritus (r = 0.44, p value ≤ 0.05). Conclusions: We report, for the first time, role of these proteins (NGF/TrK A) in the mechanism of pruritus in cirrhotic patients and may provide a potential target for new treatment of pruritus in cirrhotic.
文摘[Objectives]To observe and analyze the clinical efficacy and possible mechanism of Chuanbai antipruritic lotion"water film"wet compress combined with chloramphenicol prednisone liniment in the treatment of acute eczema.[Methods]A total of 76 acute eczema cases admitted to Shiyan Taihe Hospital from January 2022 to March 2023 were divided into Western medicine treatment group and integrated traditional Chinese and Western medicine group.In the Western medicine treatment group,chloramphenicol and prednisone liniment was applied to the skin lesions and oral administration of cetirizine hydrochloride.The course of treatment in both groups was 2 weeks(w).The levels of interferon-γ(IFN-γ),interleukin-4(IL-4)and the ratio of IFN-γ/IL-4 in the peripheral blood of patients before and 2 weeks after treatment,as well as serum immunoglobulin E(IgE),anti-IgE antibody and histamine(HA)level,and with skin lesions disappearing time,skin oil,transepidermal water loss(TEWL),eczema area and severity index(EASI)score,total effective rate,degree of pruritus and traditional Chinese medicine quality of life scale(EPQOLS)score to evaluate the efficacy.[Results]Compared with the Western medicine treatment group at 2 w,the disappearance time of skin lesions in the integrated traditional Chinese and Western medicine group was shortened,TEWL,itching degree and EASI score,serum IgE and HA,and peripheral blood IL-4 levels were all decreased(P<0.05).IFN-γand IFN-γ/IL-4 ratio,anti-IgE antibody,EPQOLS score and total effective rate were all increased(P<0.05),and the difference was statistically significant.[Conclusions]Chuanbai antipruritic lotion"water film"wet compress combined with chloramphenicol prednisone liniment is an optimized and safe and efficient method for the treatment of acute eczema,which can quickly relieve the symptoms of inflammatory damage of eczema and restore the skin barrier function,dry dampness and relieve itch.Inhibition of the release of histamine active substances and regulation of immunity may be the main mechanisms.
