{"id":2533,"date":"2022-06-09T23:43:31","date_gmt":"2022-06-09T14:43:31","guid":{"rendered":"http:\/\/misterx95.myds.me\/?p=2533"},"modified":"2022-06-09T23:43:33","modified_gmt":"2022-06-09T14:43:33","slug":"journal-club-2022-06-10","status":"publish","type":"post","link":"https:\/\/misterx95.myds.me\/wordpress\/?p=2533","title":{"rendered":"Journal Club-2022.06.10"},"content":{"rendered":"\n<h2>The role of Na\u00a0<sub>v<\/sub>\u00a01.7 and methylglyoxal-mediated activation of TRPA1 in itch and hypoalgesia in a murine model of type 1 diabetes<\/h2>\n\n\n\n<p>Ruo-Xiao Cheng, Yu Feng, Di Liu, Zhi-Hong Wang, Jiang-Tao Zhang, Li-Hua Chen, Cun-Jin Su, Bing Wang, Ya Huang, Ru-Rong Ji, Ji Hu, Tong Liu<\/p>\n\n\n\n<p><\/p>\n\n\n\n<h2>Abstract<\/h2>\n\n\n\n<p>Methylglyoxal (MGO), an endogenous reactive carbonyl compound, plays a key role in the pathogenesis of diabetic neuropathy. The aim of this study is to investigate the role of MGO in diabetic itch and hypoalgesia, two common symptoms associated with diabetic neuropathy.\u00a0<\/p>\n\n\n\n<p><strong>Methods<\/strong>: Scratching behavior, mechanical itch (alloknesis), and thermal hypoalgesia were quantified after intradermal (i.d.) injection of MGO in na\u00efve mice or in diabetic mice induced by intraperitoneal (i.p.) injection of streptozotocin (STZ). Behavioral testing, patch-clamp recording, transgenic mice, and gene expression analysis were used to investigate the mechanisms underlying diabetic itch and hypoalgesia in mice.\u00a0<\/p>\n\n\n\n<p><strong>Results<\/strong>: I.d. injection of MGO evoked dose-dependent scratching in normal mice. Addition of MGO directly activated transient receptor potential ankyrin 1 (TRPA1) to induce inward currents and calcium influx in dorsal root ganglia (DRG) neurons or in TRPA1-expressing HEK293 cells. Mechanical itch, but not spontaneous itch was developed in STZ-induced diabetic mice. Genetic ablation of\u00a0<em>Trpa1<\/em>\u00a0(<em>Trpa1<sup>-\/-<\/sup><\/em>\u00a0), pharmacological blockade of TRPA1 and Na<sub>v<\/sub>1.7, antioxidants, and mitogen-activated protein kinase kinase enzyme (MEK) inhibitor U0126 abrogated itch induced by MGO or in STZ-induced diabetic mice. Thermal hypoalgesia was induced by intrathecal (i.t.) injection of MGO or in STZ-induced diabetic mice, which was abolished by MGO scavengers, intrathecal injection of TRPA1 blockers, and in\u00a0<em>Trpa1<sup>-\/-<\/sup><\/em>\u00a0mice.\u00a0<\/p>\n\n\n\n<p><strong>Conclusion<\/strong>: This study revealed that Na<sub>v<\/sub>1.7 and MGO-mediated activation of TRPA1 play key roles in itch and hypoalgesia in a murine model of type 1 diabetes. Thereby, we provide a novel potential therapeutic strategy for the treatment of itch and hypoalgesia induced by diabetic neuropathy.<\/p>\n\n\n\n<p><strong>Keywords:\u00a0<\/strong>Diabetes; Hypoalgesia; Itch; Methylglyoxal; TRPA1.<\/p>\n\n\n\n<p><\/p>\n\n\n\n<div class=\"wp-block-file\"><a href=\"http:\/\/misterx95.myds.me\/wordpress\/wp-content\/uploads\/2022\/06\/The-role-of-Nav-1.7-and-methylglyoxal-mediated-activation-of-TRPA1-in-itch-and-hypoalgesia-in-murine-model-of-type-1-diabetes.pdf\">The role of Nav1.7 and methylglyoxal mediated activation of TRPA1 in itch and hypoalgesia in murine model of type-1 diabetes<\/a><a href=\"http:\/\/misterx95.myds.me\/wordpress\/wp-content\/uploads\/2022\/06\/The-role-of-Nav-1.7-and-methylglyoxal-mediated-activation-of-TRPA1-in-itch-and-hypoalgesia-in-murine-model-of-type-1-diabetes.pdf\" class=\"wp-block-file__button\" download>Download<\/a><\/div>\n\n\n\n<div class=\"wp-block-file\"><a href=\"http:\/\/misterx95.myds.me\/wordpress\/wp-content\/uploads\/2022\/06\/Supplementary-Information.pdf\">Supplementary Information<\/a><a href=\"http:\/\/misterx95.myds.me\/wordpress\/wp-content\/uploads\/2022\/06\/Supplementary-Information.pdf\" class=\"wp-block-file__button\" download>Download<\/a><\/div>\n","protected":false},"excerpt":{"rendered":"<p>The role of Na\u00a0v\u00a01.7 and methylglyoxal-mediated activation of TRPA1 in itch and hypoalgesia in a murine model of type 1 diabetes Ruo-Xiao Cheng, Yu Feng, Di Liu, Zhi-Hong Wang, Jiang-Tao Zhang, Li-Hua Chen, Cun-Jin Su, Bing Wang, Ya Huang, Ru-Rong Ji, Ji Hu, Tong Liu Abstract Methylglyoxal (MGO), an endogenous reactive carbonyl compound, plays a [&hellip;]<\/p>\n","protected":false},"author":7,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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