Itch (Philadelphia, Pa.)最新文献

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A systematic review of animal models and sex as a variable in itch research 动物模型和性别作为瘙痒研究变量的系统综述

Itch (Philadelphia, Pa.)

Pub Date : 2020-07-01 DOI: 10.1097/itx.0000000000000040

Joshua J. Wheeler, Katherine Allen-Moyer, John M. Davis, S. Mishra

Introduction: Pruritus (or itch) research has gained momentum in the last decades and use of animal models to study itch behavior are a vital part of the research. Recent studies have found that many fields using animal models, including neuroscience, are predisposed toward using male animals in preclinical research. To address sex bias in animal research, the National Institutes of Health (NIH) began requiring researchers to include sex as a variable beginning in June 2015. Here, we test whether researchers studying itch are biased toward using males in preclinical research. Methods: The NIH’s PubMed database was searched for primary research articles written between August 2007 and December 2018 using the words “Itch” and “Pruritus.” The following information was extracted from articles fitting our inclusion criteria: type of itch (acute or chronic), the animal model and the sex of the animals used, and whether researchers considered sex as a variable. z-Tests, binomial tests, and the Cochran-Armitage test for trend were used to explore relationships between animal models and the usage of both sexes. Results: We found 5.3%±1.2% of papers in a given year used 1 of our 4 animal models. Mice were the most frequently used animal model, followed by rats, nonhuman primates, and dogs. Overall, researchers used male animals regardless of the animal model used. In preclinical research conducted on both male and female animals, sex was not considered a variable in a majority of these studies. Finally, since 2015, there has not been a change in the usage of male or female mice. Briefly, the incidence of papers utilizing both sexes has not changed. Discussion: We have found that itch researchers have a bias towards males in animal research. This bias has not changed since the NIH’s mandate to include sex as a variable in preclinical research.

引言：瘙痒（或瘙痒）研究在过去几十年中取得了进展，使用动物模型研究瘙痒行为是该研究的重要组成部分。最近的研究发现，包括神经科学在内的许多使用动物模型的领域都倾向于在临床前研究中使用雄性动物。为了解决动物研究中的性别偏见，美国国立卫生研究院（NIH）从2015年6月开始要求研究人员将性别作为一个变量。在这里，我们测试研究瘙痒的研究人员是否倾向于在临床前研究中使用男性。方法：在美国国立卫生研究院的PubMed数据库中搜索2007年8月至2018年12月期间使用“瘙痒”和“瘙痒”两个词撰写的主要研究文章。从符合我们纳入标准的文章中提取以下信息：瘙痒类型（急性或慢性）、动物模型和所用动物的性别，以及研究人员是否将性别视为一个变量。z检验、二项式检验和趋势的Cochran-Armitage检验用于探索动物模型与两性使用之间的关系。结果：我们发现，在一年中，5.3%±1.2%的论文使用了我们4种动物模型中的1种。小鼠是最常用的动物模型，其次是大鼠、非人类灵长类动物和狗。总的来说，研究人员使用雄性动物，而不考虑使用的动物模型。在对雄性和雌性动物进行的临床前研究中，大多数研究都不认为性别是一个变量。最后，自2015年以来，雄性或雌性小鼠的使用情况没有变化。简言之，利用两性的论文发生率没有改变。讨论：我们发现瘙痒研究人员在动物研究中对雄性有偏见。自从美国国立卫生研究院授权将性别作为临床前研究的一个变量以来，这种偏见一直没有改变。

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引用次数: 4

A review of the management of uremic pruritus: current perspectives and future directions 尿毒症瘙痒症的治疗综述：现状与发展方向

Itch (Philadelphia, Pa.)

Pub Date : 2020-07-01 DOI: 10.1097/itx.0000000000000038

E. Westby, K. Purdy, K. Tennankore

Uremic pruritus (UP) is a common and distressing symptom experienced by up to half of all patients with end-stage renal disease (ESRD) receiving dialysis. It is associated with multiple health-related quality of life impairments and has been independently associated with mortality. Despite the prevalence and associated impact on quality of life, UP remains a difficult symptom to treat because of the relative lack of existing high quality evidence on which to base recommendations and the sheer volume of poorly studied therapeutic options. This review outlines the existing data of available treatment options including topical therapy, systemic therapy, and phototherapy as well as explore emerging data on therapies that are targeting novel pruritus pathways including the cannabinoid and opioid pathways. Overall, neuromodulators, in particular gabapentin, appear to have the most robust data in the treatment of UP. In individuals who cannot tolerate oral systemic therapy or in those with refractory generalized UP, ultraviolet phototherapy, specifically broad-band UVB, has shown significant promise. However, access is often a limiting factor. Lastly, the emergence of new therapies targeting a peripheral acting κ-opioid agonist, difelikefalin, has demonstrated effect in both early phase 2 and 3 clinical trials.

尿毒症瘙痒（UP）是一种常见且令人痛苦的症状，在接受透析的终末期肾病（ESRD）患者中，多达一半的患者都会出现这种症状。它与多种与健康相关的生活质量障碍有关，并与死亡率独立相关。尽管UP的患病率和对生活质量的相关影响，但它仍然是一种难以治疗的症状，因为相对缺乏现有的高质量证据作为建议的基础，而且研究不足的治疗方案数量之多。这篇综述概述了可用治疗方案的现有数据，包括局部治疗、全身治疗和光疗，并探索了针对新型瘙痒途径的治疗新数据，包括大麻素和阿片类药物途径。总的来说，神经调节剂，特别是加巴喷丁，似乎在UP的治疗中拥有最有力的数据。在无法耐受口服全身治疗的个体或难治性全身性UP患者中，紫外线光疗，特别是宽带UVB，显示出显著的前景。然而，访问往往是一个限制因素。最后，针对外周作用κ-阿片类激动剂二氟吡唑林的新疗法的出现，已在早期2期和3期临床试验中证明了效果。

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引用次数: 5

Sex differences in the perception of itch and quality of life in patients with chronic pruritus in the United States 美国慢性瘙痒症患者瘙痒感和生活质量的性别差异

Itch (Philadelphia, Pa.)

Pub Date : 2020-07-01 DOI: 10.1097/itx.0000000000000041

C. Kursewicz, E. Fowler, J. Rosen, D. Castillo, Y. Chan, L. Nattkemper, G. Yosipovitch

Using cross-sectional survey data from 335 patients with chronic itch, we analyzed differences in itch intensity, characteristics, and quality of life between males and females. The intensity of chronic pruritus was significantly greater in females compared with males (7.70 vs. 6.95; P<0.05) and females more often described their pruritus as dreadful, unbearable, hurting, and oppressive (P<0.05). In addition, females achieved a greater overall quality of life mean score compared with males (3.65 vs. 3.19; P<0.05), indicating a more negative impact on quality of life. Overall, our study shows that significant differences exist between females and males with chronic pruritus, and clinicians should be aware of these distinctions.

利用335名慢性瘙痒患者的横断面调查数据，我们分析了男性和女性在瘙痒强度、特征和生活质量方面的差异。女性的慢性瘙痒强度明显高于男性（7.70 vs.6.95；P<0.05），女性更经常将自己的瘙痒描述为可怕、难以忍受、疼痛和压迫（P<0.05）。此外，与男性相比，女性的总体生活质量平均得分更高（3.65 vs.3.19；P<0.05），这表明对生活质量的负面影响更大。总的来说，我们的研究表明，患有慢性瘙痒症的女性和男性之间存在显著差异，临床医生应该意识到这些差异。

引用次数: 2

Loss of S1PR3 attenuates scratching behaviors in mice in the imiquimod model of psoriasis, but not in the MC903 model of atopic dermatitis S1PR3的缺失减轻了咪喹莫特银屑病模型小鼠的抓挠行为，但在MC903特应性皮炎模型中没有

Itch (Philadelphia, Pa.)

Pub Date : 2020-04-01 DOI: 10.1097/itx.0000000000000035

Rose Z. Hill, Ziad Rifi, Cliff Vuong, D. Bautista

Here we examine the role of sphingosine 1-phosphate receptor 3 (S1PR3) in chronic itch. We used 2 mouse models—the MC903 model of atopic dermatitis and the imiquimod model of psoriasis—to examine the contribution of S1PR3 to chronic itch. We measured scratching behaviors in these mouse models in S1PR3−/−, +/−, and +/+ animals. Whereas we observed no effect of loss of S1PR3 on itch behaviors in the MC903 model, imiquimod-evoked itch behaviors were reduced in S1PR3−/− animals. Overall, the data support a role for S1PR3 signaling in the development of psoriatic but not atopic itch.

在这里，我们研究鞘氨醇1-磷酸受体3 (S1PR3)在慢性瘙痒中的作用。我们使用2种小鼠模型-特应性皮炎的MC903模型和银屑病的咪喹莫特模型-来研究S1PR3对慢性瘙痒的贡献。我们测量了这些小鼠模型中S1PR3−/−、+/−和+/+动物的抓痕行为。虽然我们在MC903模型中没有观察到S1PR3缺失对瘙痒行为的影响，但在S1PR3−/−动物中，咪喹莫德诱发的瘙痒行为有所减少。总的来说，这些数据支持S1PR3信号在银屑病而非特应性瘙痒的发展中发挥作用。

引用次数: 3

Itch intensity and characteristics in fibromyalgia patients in an outpatient rheumatology clinic 风湿病门诊纤维肌痛患者的瘙痒强度和特征

Itch (Philadelphia, Pa.)

Pub Date : 2020-04-01 DOI: 10.1097/itx.0000000000000033

S. Shah, R. S. Golpanian, T. Hashimoto, J. Rosen, L. Nattkemper, C. Albornoz, Y. Chan, G. Yosipovitch

Supplemental Digital Content is available in the text. Fibromyalgia (FM) is a disease characterized by chronic widespread pain and tenderness for at least 3 months and is associated with various dermatologic symptoms including itch. This study investigated the prevalence and characteristics of itch in female FM patients and whether or not it correlated to their pain. Our data revealed that 60% of FM patients in an outpatient rheumatology clinic suffered from chronic itch. Itch intensity had no correlation with pain intensity, but it was associated with both sleep disturbance and quality of life impairment. Also, itch intensity had no correlation with the intake of gamma aminobutyric acidergic or antidepressant drugs.

文本中提供了补充数字内容。纤维肌痛（FM）是一种以慢性广泛疼痛和压痛至少3个月为特征的疾病，并与包括瘙痒在内的各种皮肤病症状有关。本研究调查了女性FM患者瘙痒的患病率和特征，以及瘙痒是否与疼痛相关。我们的数据显示，在门诊风湿病诊所，60%的FM患者患有慢性瘙痒。瘙痒强度与疼痛强度无关，但与睡眠障碍和生活质量受损有关。此外，瘙痒强度与γ-氨基丁酸能或抗抑郁药物的摄入无关。

引用次数: 0

Nonpharmacologic interventions for chronic pruritus 慢性瘙痒的非药物干预

Itch (Philadelphia, Pa.)

Pub Date : 2020-01-01 DOI: 10.1097/itx.0000000000000031

J. Bonchak, P. Lio

Chronic pruritus, traditionally defined as itch persisting for >6 weeks, is a common affliction that can be associated with cutaneous or systemic disease, or may be idiopathic in nature. It affects patients of all ages and backgrounds and seems to have no predilection for sex or socioeconomic status. The lifetime prevalence has been estimated between 22% and 26%. It accounts for millions of outpatient clinic encounters every year. Pruritus is associated with significant morbidity ranging from sleep disturbance to suicidal ideation in both pediatric and adult patients. The pathophysiology of pruritus is complex and multifactorial. An intricate and incompletely understood interplay between cytokines, sensory neurons, and a variety of cutaneous and central nervous system receptors and effector cells are responsible for the development of itch. Scores of therapies exist, with enormous variation in efficacy, for the amelioration of itch. Drugs aimed at virtually all of the aforementioned pathogenic factors in pruritus have been trialed or are being developed. Nonpharmacologic therapies for chronic pruritus encompass a variety of methods for altering itch signaling or for changing the patient’s perception of pruritus. Although some of these interventions may be used as monotherapy, they are usually best utilized in combination with more conventional pharmacologic antipruritic therapies. This review evaluates the current understanding of the mechanisms and efficacy of these nonpharmacologic interventions and serves to expand the dermatologist's armamentarium against chronic pruritus.

慢性瘙痒，传统上定义为瘙痒持续60 - 60周，是一种常见的痛苦，可与皮肤或全身性疾病有关，也可能是特发性的。它影响所有年龄和背景的患者，似乎没有性别或社会经济地位的偏好。终生患病率估计在22%至26%之间。每年有数以百万计的门诊病例。瘙痒症在儿童和成人患者中与从睡眠障碍到自杀意念的显著发病率相关。瘙痒症的病理生理是复杂的、多因素的。细胞因子、感觉神经元、各种皮肤和中枢神经系统受体和效应细胞之间复杂而不完全理解的相互作用负责瘙痒的发展。为了改善瘙痒，存在着几十种治疗方法，其疗效差异很大。针对上述所有瘙痒症致病因素的药物已经试验或正在开发中。慢性瘙痒的非药物治疗包括改变瘙痒信号或改变患者对瘙痒的感觉的各种方法。虽然其中一些干预措施可以作为单一疗法使用，但它们通常最好与更传统的药理学止痒疗法联合使用。这篇综述评估了目前对这些非药物干预的机制和疗效的理解，并有助于扩大皮肤科医生对慢性瘙痒的治疗手段。

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引用次数: 1

Measurement tools for chronic pruritus: assessment of the symptom and the associated burden: a review 慢性瘙痒的测量工具:症状和相关负担的评估:综述

Itch (Philadelphia, Pa.)

Pub Date : 2019-10-01 DOI: 10.1097/itx.0000000000000029

M. Pereira, S. Ständer

Chronic pruritus is a subjective, multidimensional and highly impairing symptom of difficult assessment. Its clinical features and secondary burdens may vary substantially between affected individuals and within the same patient across time. Standardized scales and questionnaires have been developed to assess the various dimensions of chronic pruritus. Instruments addressing the intensity, distribution, qualities of associated symptoms, skin status and course over time are available for clinical trials. In addition, patient-oriented questionnaires on reactive conditions, including sleep disorders, anxiety, depression, and impairment of quality of life can be used. Assessing the individual patient’s needs before and throughout the treatment is valuable in directing therapeutic priorities and maximizing patient’s satisfaction. Along with a detailed medical history and a comprehensive physical examination, these instruments should be implemented in the clinical routine to achieve a comprehensive assessment of each patient. European experts of the European Academy of Dermatology and Venereology (EADV) considered a priority the use of intensity scales and questionnaires on quality of life. Harmonization of the assessment procedures should be aimed for across attending physicians. New technologies including electronic diaries or the use of tablet computers to complete assessment tools constitute helpful aids in the clinical practice by facilitating data collection and saving time.

慢性瘙痒是一种主观的、多方面的、高度损害的、难以评估的症状。其临床特征和继发负担可能在受影响个体之间以及同一患者在不同时间内存在很大差异。标准化的量表和调查问卷已被开发来评估慢性瘙痒的各个方面。针对强度、分布、相关症状质量、皮肤状况和病程的仪器可用于临床试验。此外，还可以使用以患者为导向的反应性疾病问卷，包括睡眠障碍、焦虑、抑郁和生活质量受损。在治疗前和整个治疗过程中评估个体患者的需求对于指导治疗重点和最大限度地提高患者满意度是有价值的。除了详细的病史和全面的体格检查外，这些仪器应在临床常规中实施，以实现对每位患者的全面评估。欧洲皮肤病和性病学会(EADV)的欧洲专家们优先考虑使用强度量表和生活质量调查问卷。评估程序的协调应针对所有主治医生。包括电子日记或使用平板电脑来完成评估工具在内的新技术通过促进数据收集和节省时间，在临床实践中构成了有益的辅助手段。

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引用次数: 3

Placebo and nocebo effects on itch: a review of experimental methods 安慰剂和反安慰剂对瘙痒的影响:实验方法综述

Itch (Philadelphia, Pa.)

Pub Date : 2019-07-01 DOI: 10.1097/itx.0000000000000027

Joseph S. Blythe, K. Peerdeman, D. Veldhuijzen, A. V. Van Laarhoven, A. Evers

Itch is a commonly experienced symptom of acute and chronic dermatological and systemic conditions. Placebo and nocebo effects, positive and negative effects experienced after both real and sham interventions, putatively due to positive or negative outcome expectancies, can have a significant impact on the experience of itch and its treatment. Experimental methods to induce and study placebo and nocebo effects on itch have been developed, utilizing various combinations of expectancy-induction methods (eg, conditioning, verbal suggestions) and short-acting itch-evoking stimuli (eg, histamine, electrical, or mechanical stimulation). The aim of this review is to describe the current research methods used to induce placebo and nocebo effects on itch, and the results of these studies. The benefits and drawbacks of different expectancy-induction methods and itch-evoking stimuli are described, and future directions for research and clinical application are discussed.

瘙痒是急性和慢性皮肤病和全身疾病的常见症状。安慰剂和反安慰剂效应，在真实和虚假干预后经历的积极和消极影响，假定是由于积极或消极的结果预期，可以对瘙痒体验及其治疗产生重大影响。诱导和研究安慰剂和反安慰剂对瘙痒影响的实验方法已经开发出来，利用各种期望诱导方法(例如，条件反射，口头建议)和短效瘙痒刺激(例如，组胺，电或机械刺激)的组合。本综述的目的是描述目前用于诱导安慰剂和反安慰剂对瘙痒的影响的研究方法，以及这些研究的结果。介绍了不同期望诱导方法和瘙痒诱发刺激的优缺点，并对未来的研究和临床应用方向进行了讨论。

引用次数: 15

Signs of chronic itch in the mouse imiquimod model of psoriasiform dermatitis: sex differences and roles of TRPV1 and TRPA1. 银屑病样皮炎小鼠咪喹莫特模型的慢性瘙痒症状:TRPV1和TRPA1的性别差异和作用

Itch (Philadelphia, Pa.)

Pub Date : 2019-07-01 DOI: 10.1097/itx.0000000000000025

Taylor Follansbee, Yan Zhou, Xuesong Wu, Jeremy Delahanty, Amanda Nguyen, Dan Domocos, Mirela Iodi Carstens, Samuel T Hwang, Earl Carstens

Plaque psoriasis is a chronic inflammatory skin disease that affects a substantial proportion of the world population. This disorder is characterized by scaly, thick skin, intense ongoing itch, and itch from light touch (such as clothing contacting skin, called "alloknesis"). Imiquimod is a topical treatment for basal cell carcinomas and warts that has been used to create a mouse model of plaque psoriasis. Imiquimod-treated male, but not female, wildtype B6 mice showed significant increases in spontaneous scratching, while both sexes exhibited increased alloknesis, indicative of chronic itch. TRPV1 and TRPA1 knockout (KO) mice all exhibited numeric increases in spontaneous scratching which were significant for TRPV1KO mice and TRPA1KO males. Female TRPV1KO and TRPA1KO mice exhibited imiquimod-induced increases in alloknesis scores that did not significantly differ from wildtypes, while alloknesis scores in imiquimod-treated male TRPV1KO and TRPA1KO mice were significantly lower compared with wildtypes, suggesting that these ion channels are necessary for the development of alloknesis in males but not females in this model. Curiously, none of the groups exhibited any significant overall change in chloroquine-evoked scratching following imiquimod treatment, indicating that hyperknesis does not develop in this mouse model. Overall, the data indicate that there are sex differences in this mouse model of psoriasis, and that TRPV1 and TRPA1 ion channels have a small role in promoting the development of itch sensitization. This contrasts with the far greater role these channels play in the manifestation of skin changes in psoriatic dermatitis.

斑块型银屑病是一种慢性炎症性皮肤病，影响着世界上相当大比例的人口。这种疾病的特征是鳞状、厚皮肤、持续强烈的瘙痒和轻触(如衣服接触皮肤，称为“异位性”)引起的瘙痒。咪喹莫特是一种局部治疗基底细胞癌和疣的药物，已被用于创建斑块型银屑病的小鼠模型。吡喹莫德处理过的雄性野生型B6小鼠自发抓挠明显增加，雌性野生型B6小鼠自发抓挠明显增加，两性均表现出异位性增加，表明慢性瘙痒。TRPV1和TRPA1基因敲除(KO)小鼠自发抓痕的数量均增加，这在TRPV1KO小鼠和TRPA1KO雄性小鼠中都是显著的。雌性TRPV1KO和TRPA1KO小鼠表现出吡喹莫德诱导的异基因得分升高，与野生型相比差异不显著，而雄性TRPV1KO和TRPA1KO小鼠的异基因得分明显低于野生型，这表明在该模型中，这些离子通道是雄性异基因发生所必需的，而雌性则不是。奇怪的是，在咪喹莫特治疗后，没有一个组在氯喹引起的抓痕方面表现出任何显著的整体变化，这表明在该小鼠模型中没有发生过度呼吸。综上所述，这些数据表明，该银屑病小鼠模型存在性别差异，TRPV1和TRPA1离子通道在促进瘙痒致敏的发展中具有较小的作用。这与这些通道在银屑病皮炎的皮肤变化表现中发挥的更大作用形成对比。

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引用次数: 10

MrgprX1 Mediates Neuronal Excitability and Itch Through Tetrodotoxin-Resistant Sodium Channels. MrgprX1通过抗河豚毒素钠通道介导神经元兴奋性和瘙痒。

Itch (Philadelphia, Pa.)

Pub Date : 2019-07-01 Epub Date: 2019-08-01 DOI: 10.1097/itx.0000000000000028

Pang-Yen Tseng, Qin Zheng, Zhe Li, Xinzhong Dong

In this study, we sought to elucidate the molecular mechanism underlying human Mas-related G protein-coupled receptor X1 (MrgprX1) mediated itch sensation. We found that activation of MrgprX1 by BAM8-22 triggered robust action potential discharges in dorsal root ganglion (DRG) neurons. This neuronal excitability is not mediated by Transient receptor potential (TRP) cation channels, M-type potassium channels, or chloride channels. Instead, activation of MrgprX1 lowers the activation threshold of TTX-resistant sodium channels and induces inward sodium currents. These MrgprX1-elicited action potential discharges can be blocked by Pertussis toxin (PTX) and a Gβγ inhibitor - Gallein. Behavioral results showed that Nav1.9 knockout but not Trpa1 knockout significantly reduced BAM8-22 evoked scratching behavior. Collectively, these data suggest that activation of MrgprX1 triggers itch sensation by increasing the activity of TTX-resistant voltage-gated sodium channels.

在这项研究中，我们试图阐明人类mass相关G蛋白偶联受体X1 (MrgprX1)介导瘙痒感觉的分子机制。我们发现BAM8-22激活MrgprX1会在背根神经节(DRG)神经元中触发强大的动作电位放电。这种神经元兴奋性不是由瞬时受体电位(TRP)阳离子通道、m型钾通道或氯离子通道介导的。相反，MrgprX1的激活降低了抗ttx钠通道的激活阈值，并诱导向内钠电流。这些mrgprx1引起的动作电位放电可被百日咳毒素(PTX)和Gβγ抑制剂Gallein阻断。行为学结果显示，敲除Nav1.9而不敲除Trpa1显著降低了BAM8-22引起的抓痕行为。总的来说，这些数据表明MrgprX1的激活通过增加抗ttx电压门控钠通道的活性来触发瘙痒感觉。

引用次数: 17

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