Itch (Philadelphia, Pa.)最新文献

Kappa opioid agonists in the treatment of itch: just scratching the surface? Kappa 阿片受体激动剂治疗瘙痒：仅仅是表面现象？

Itch (Philadelphia, Pa.) Pub Date : 2023-10-01 Epub Date: 2023-12-06 DOI: 10.1097/itx.0000000000000072

Tyler C Beck, Elena M Wilson, Erik Wilkes, Lara Wine Lee, Russell Norris, Manuel Valdebran

{"title":"Kappa opioid agonists in the treatment of itch: just scratching the surface?","authors":"Tyler C Beck, Elena M Wilson, Erik Wilkes, Lara Wine Lee, Russell Norris, Manuel Valdebran","doi":"10.1097/itx.0000000000000072","DOIUrl":"https://doi.org/10.1097/itx.0000000000000072","url":null,"abstract":"<p><p>Chronic pruritus is a debilitating condition affecting 23-44 million Americans. Recently, kappa opioid agonists (KOAs) have emerged as a novel class of potent antipruritic agents. In 2021, the Food and Drug Administration approved difelikefalin (Korsuva) for the treatment of moderate-to-severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis. Difelikefalin is a potent, peripherally restricted KOA that is intravenously available. Although promising, difelikefalin is currently available as an intravenous composition only, limiting the scope of use. Oral formulations of difelikefalin did not meet the primary endpoint criteria in recent phase 2 clinical trials; however, additional clinical studies are ongoing. The future for KOAs in the treatment of pruritus is encouraging. Orally active pathway-biased KOAs, such as triazole 1.1, may serve as viable alternatives with broader applications. Extended-release compositions, such as the TP-2021 ProNeura subdermal implant, may circumvent the pharmacokinetic issues associated with peptide-based KOAs. Lastly, dual-acting kappa opioid receptor agonist/mu opioid receptor antagonists are orally bioavailable and may be useful in the treatment of various forms of chronic itch. In this review, we summarize the results of KOAs in clinical and preclinical trials and discuss future directions of drug development.</p>","PeriodicalId":73523,"journal":{"name":"Itch (Philadelphia, Pa.)","volume":"8 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10720604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138815245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Real-world clinical efficacy of nemolizumab in Japanese patients with atopic dermatitis 奈莫单抗在日本特应性皮炎患者中的实际临床疗效

Itch (Philadelphia, Pa.) Pub Date : 2023-10-01 DOI: 10.1097/itx.0000000000000071

Yoshinori Watanabe, Yozo Ishiuji, Minako Ogawa-Tominaga, Michie Katsuta, Akihiko Asahina

引用次数: 0

Oral administration of 4′-demethyl nobiletin inhibits dry skin-induced mechanical alloknesis 口服4′-去甲基皂素可抑制皮肤干燥引起的机械变形

Itch (Philadelphia, Pa.) Pub Date : 2023-07-01 DOI: 10.1097/itx.0000000000000069

S. Toyama, M. Tominaga, E. Komiya, S. Kusano, T. Kaneko, K. Takamori

引用次数: 0

The effect of repetitive topical applications of local anesthetics (EMLA) on experimental pain and itch (histaminergic and nonhistaminergic) 反复局部应用局部麻醉剂（EMLA）对实验性疼痛和瘙痒（组胺能和非组胺能）的影响

Itch (Philadelphia, Pa.) Pub Date : 2023-04-01 DOI: 10.1097/itx.0000000000000070

Giulia Erica Aliotta, S. L. Vecchio, J. Elberling, L. Arendt-Nielsen

{"title":"The effect of repetitive topical applications of local anesthetics (EMLA) on experimental pain and itch (histaminergic and nonhistaminergic)","authors":"Giulia Erica Aliotta, S. L. Vecchio, J. Elberling, L. Arendt-Nielsen","doi":"10.1097/itx.0000000000000070","DOIUrl":"https://doi.org/10.1097/itx.0000000000000070","url":null,"abstract":"Background: The effects of repeated topical applications of local anesthetics are poorly investigated as they may, in addition to analgesia, impact peripheral nerve endings in a cumulative manner. In the present study, the effects of 6 repetitive applications of eutectic mixture of lidocaine (EMLA 2.5% and prilocaine 2.5%) were investigated on experimentally induced pain, histaminergic and nonhistaminergic itch, and neurogenic inflammation. Methods: Four skin areas on the forearms of 24 subjects were randomized to receive 3 hours of application of EMLA or placebo twice a day for 3 consecutive days. After each application, superficial blood perfusion (SBP), mechanical (mechanically evoked itch, mechanical pain threshold, and mechanical pain sensitivity), and thermal sensitivity (warm detection threshold, heat pain threshold, and suprathreshold heat sensitivity) were assessed. After the last application of EMLA/placebo, histamine and cowhage was applied (2 areas each) and itch and pain intensity and SBP were assessed. Results: After 3 hours of EMLA application, significant mechanical and thermal hypoalgesia were found with no cumulative efficacy over the 3 days. EMLA alone had no effect on SBP. Significantly increased SBP, reduced cowhage-induced itch, but the unaffected histamine-induced itch was found when applying EMLA ahead of histamine and cowhage. Conclusions: EMLA induced a reduction of mechanical and thermal sensitivity without a cumulative-dose effect. EMLA reduced nonhistaminergic itch and pain but not the experimentally provoked histaminergic itch. Selective action of EMLA on polymodal C-fibers could explain these effects.","PeriodicalId":73523,"journal":{"name":"Itch (Philadelphia, Pa.)","volume":"8 1","pages":"e70 - e70"},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44328802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Potential antipruritic neuronal targets of nalfurafine in the murine spinal dorsal horn 纳氟萘芬在小鼠脊髓背角的潜在抗瘙痒神经元靶点

Itch (Philadelphia, Pa.) Pub Date : 2023-01-01 DOI: 10.1097/itx.0000000000000066

K. Honda, M. Tominaga, F. Kusube, K. Takamori

{"title":"Potential antipruritic neuronal targets of nalfurafine in the murine spinal dorsal horn","authors":"K. Honda, M. Tominaga, F. Kusube, K. Takamori","doi":"10.1097/itx.0000000000000066","DOIUrl":"https://doi.org/10.1097/itx.0000000000000066","url":null,"abstract":"Introduction: Itch is an unpleasant sensation that evokes a scratching behavior which often damages the skin. Nalfurafine is a kappa opioid receptor (KOR) agonist known as an effective drug used to control the intractable itch. Mechanistically, the spinal cord is a target of nalfurafine, however, little is known about the specific sites important to the antipruritic effects of nalfurafine. Therefore, the aim of this study was an investigation to uncover the sites of action of nalfurafine in the spinal neuronal pathway of itch. Materials and Methods: To reveal the antipruritic action of nalfurafine in the murine spinal dorsal horn, we conducted in vivo electrophysiology, behavioral experiments, and high-sensitive in situ hybridization (ISH) using normal C57BL/6J mice. Results: Behavioral analyses indicated that intrathecal injection of nalfurafine reduced, but not entirely eliminated the gastrin-releasing peptide (GRP)-evoked scratching bouts. In vivo electrophysiological recordings revealed that nalfurafine administration suppressed chloroquine (CQ)-responsive dorsal horn neurons in 15.8% (3/19) of mice. In fact, only 1 of 3 nalfurafine-suppressed mice responded to GRP. ISH in 3 sections of the spinal cord showed that 24.8% (154/623) were double-positive for GRP and KOR and 13.6% (68/431) for GRP receptor (GRPR) and KOR in total KOR+ cells. Most KOR+ cells were negative for GRP and GRPR. Intrathecal injection of dynorphin-saporin did not change the number of scratching bouts caused by GRP. However, it reduced the number of scratching bouts evoked by intradermal injection of CQ. Discussion: In conclusion, our data suggest that nalfurafine targets both GRP+ KOR+ and GRPR+ KOR+ cells which are present in a 2:1 ratio and suppresses CQ-induced itch in the spinal dorsal horn. These findings suggest that GRP+ KOR- or GRPR+ KOR- cells may function as interneurons in the spinal neuronal pathway of itch.","PeriodicalId":73523,"journal":{"name":"Itch (Philadelphia, Pa.)","volume":"8 1","pages":"e66 - e66"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43100907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Therapeutics in chronic pruritus of unknown origin 不明原因慢性瘙痒症的治疗

Itch (Philadelphia, Pa.) Pub Date : 2023-01-01 DOI: 10.1097/itx.0000000000000064

T. Ju, A. Labib, A. Vander Does, G. Yosipovitch

{"title":"Therapeutics in chronic pruritus of unknown origin","authors":"T. Ju, A. Labib, A. Vander Does, G. Yosipovitch","doi":"10.1097/itx.0000000000000064","DOIUrl":"https://doi.org/10.1097/itx.0000000000000064","url":null,"abstract":"Chronic pruritus of unknown origin (CPUO) is a common condition that is underrecognized and underdiagnosed. Patients suffer from 6 or more weeks of pruritus with no identified cause, or with multiple potential causes, of which the primary cause cannot be determined. Despite being a common condition and prevalent in nearly 30% of the elderly in certain populations, most patients suffer from CPUO for years from inadequate treatments for itch and are made to undergo extensive diagnostics. There is no FDA-approved treatment for CPUO, and providers are often tasked to treat CPUO patients with limited knowledge and guidance on CPUO and its treatments. However, recent breakthroughs in antipruritic therapeutics have led to an increase in therapies available for CPUO patients. These include a variety of both pharmacological and nonpharmacological interventions, as well as topical and systemic therapies. Newer therapies such as biologics and Janus kinase inhibitors are currently under investigation due to their therapeutic effects in other pruritic diseases and are promising for treating CPUO. Here, we review the various therapeutic options that are currently available or are on the horizon, with a special emphasis on the therapies antipruritic mechanism, available clinical evidence of efficacy and safety, and the appropriate contexts for their application. By doing so, we hope to educate clinicians on the known treatments for pruritus and their applicability to CPUO to guide optimal management of this highly prevalent disease.","PeriodicalId":73523,"journal":{"name":"Itch (Philadelphia, Pa.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45920292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The effect of escalating heat stimulation on top of anesthetized skin 在麻醉皮肤上不断升级的热刺激的效果

Itch (Philadelphia, Pa.) Pub Date : 2023-01-01 DOI: 10.1097/itx.0000000000000065

D. Riccio, S. Lo Vecchio, L. Arendt-Nielsen

引用次数: 0

Pruritic eruptions in older adults: characterization of a patch test negative cohort 老年人瘙痒性皮疹:斑贴试验阴性队列的特征

Itch (Philadelphia, Pa.) Pub Date : 2023-01-01 DOI: 10.1097/itx.0000000000000067

S. Sreekantaswamy, Jane Tully, N. Botto, Carina M. Woodruff, D. Butler

引用次数: 0

Role of antioxidants in itch treatment: lessons learned from pain management 抗氧化剂在瘙痒治疗中的作用:从疼痛管理中获得的经验教训

Itch (Philadelphia, Pa.) Pub Date : 2023-01-01 DOI: 10.1097/itx.0000000000000068

Georgia Biazus Soares, O. Mahmoud, G. Yosipovitch

引用次数: 1

Severity stages of chronic nodular prurigo: analysis of associated itch intensity and quality of life impairment 慢性结节性瘙痒症的严重程度分期：相关瘙痒强度和生活质量损害的分析

Itch (Philadelphia, Pa.) Pub Date : 2022-10-01 DOI: 10.1097/itx.0000000000000061

C. Zeidler, M. Pereira, M. Storck, Aysenur Suer, S. Ständer

{"title":"Severity stages of chronic nodular prurigo: analysis of associated itch intensity and quality of life impairment","authors":"C. Zeidler, M. Pereira, M. Storck, Aysenur Suer, S. Ständer","doi":"10.1097/itx.0000000000000061","DOIUrl":"https://doi.org/10.1097/itx.0000000000000061","url":null,"abstract":"Introduction: Chronic nodular prurigo (CNPG) is a pruritic neuroinflammatory skin disease characterized by the presence of multiple pruriginous nodules. Previous psychometric analyzes showed the presence of moderate to severe pruritus and a considerable impairment of quality of life. A detailed study of these parameters in relation to the severity of the disease defined by the number of lesions is lacking. Methods: A total of 131 adult patients with CNPG were included. The number of pruriginous lesions and disease stage was determined by using the Prurigo Activity and Severity (PAS) scale and the prurigo-specific Investigator’s Global Assessment (IGA) scale. Patient-reported outcomes comprised pruritus intensity (worst itch intensity of the previous 24 h using the numerical rating scale; WI-NRS/24 h) and the impairment of quality of life (ItchyQol, Dermatology Life Quality Index; DLQI). Results: The counted and estimated number of pruriginous nodules correlated strongly with each other (r=0.82; P<0.001), moderately with the WI-NRS/24 h (counted number: r=0.44, P<0.001; estimated number: r=0.45, P<0.001) and with the DLQI score (counted number: r=0.40, P<0.001; estimated number: r=0.38, P<0.001). The severity groups of the CNPG, as defined by the IGA scale, correlated strongly with the WINRS/24 h and DLQI scores. With increasing severity of CNPG, increasing pruritus intensity and DLQI/ItchyQoL scores were recorded. Conclusion: The correlation between objective (disease stage) and subjective (itch intensity, quality of life) CNPG disease parameters argues for a representative disease severity characterization via physician assessments using either PAS or IGA.","PeriodicalId":73523,"journal":{"name":"Itch (Philadelphia, Pa.)","volume":"7 1","pages":"e61 - e61"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47657189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0