瞬时受体电位通道Trpv1和Trpm8在糖尿病周围神经病变中的作用。

Journal of diabetes and treatment Pub Date : 2017-01-01 Epub Date: 2017-10-17
Mallikarjuna R Pabbidi, Louis S Premkumar
{"title":"瞬时受体电位通道Trpv1和Trpm8在糖尿病周围神经病变中的作用。","authors":"Mallikarjuna R Pabbidi, Louis S Premkumar","doi":"","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>1.1.Transient Receptor Potential (Vanilloid 1) TRPV1 and (Melastatin 8) TRPM8 are heat and cold sensing non-selective cation channels, respectively. We sought to correlate the modulation of TRPV1- and TRPM8-mediated membrane currents and altered thermal sensitivity in Diabetic Peripheral Neuropathy (DPN).</p><p><strong>Method: </strong>1.2.Streptozotocin (STZ)-induced diabetic mice were used and thermal (heat and cold) pain sensitivities were determined using hot plate and acetone drop test, respectively. Membrane currents were recorded using patch-clamp techniques.</p><p><strong>Results: </strong>1.3.First, we tested thermal pain sensitivities to implicate a possible role of TRPV1 and TRPM8 in DPN. Paw withdrawal latency on a hot plate test was decreased, and acetone-induced cold sensitivity was enhanced in diabetic mice as compared to non-diabetic mice. Dorsal Root Ganglion (DRG) neurons dissociated from diabetic hyperalgesic mice exhibited an increase in TRPV1-mediated current and a decrease in TRPM8-mediated currents as compared to non-diabetic mice. Then, we determined the modulation of TRPV1- and TRPM8-mediated currents using HEK cells heterologously expressing TRPV1 by promoting PKC- and PKA-mediated phosphorylation. Both Phorbol 12,13-Dibutyrate (PDBu), a PKC activator and forskolin, a PKA activator upregulated TRPV1-mediated currents but downregulated TRPM8-mediated currents. In diabetic mice, intraplantar injection of capsaicin, a TRPV1 agonist-induced nocifensive behavior but the severity of this behavior was significantly lower when co-administered with menthol, a TRPM8 agonist.</p><p><strong>Conclusions: </strong>1.4.These findings suggest that diabetic thermal hyperalgesia mediated by up-regulation of TRPV1 function may be further aggravated by the downregulation of TRPM8 function. Targeting TRPV1 may be a useful approach to alleviate pain associated with DPN.</p>","PeriodicalId":73707,"journal":{"name":"Journal of diabetes and treatment","volume":"2017 4","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317870/pdf/nihms-1002094.pdf","citationCount":"0","resultStr":"{\"title\":\"Role of Transient Receptor Potential Channels Trpv1 and Trpm8 in Diabetic Peripheral Neuropathy.\",\"authors\":\"Mallikarjuna R Pabbidi, Louis S Premkumar\",\"doi\":\"\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>1.1.Transient Receptor Potential (Vanilloid 1) TRPV1 and (Melastatin 8) TRPM8 are heat and cold sensing non-selective cation channels, respectively. We sought to correlate the modulation of TRPV1- and TRPM8-mediated membrane currents and altered thermal sensitivity in Diabetic Peripheral Neuropathy (DPN).</p><p><strong>Method: </strong>1.2.Streptozotocin (STZ)-induced diabetic mice were used and thermal (heat and cold) pain sensitivities were determined using hot plate and acetone drop test, respectively. Membrane currents were recorded using patch-clamp techniques.</p><p><strong>Results: </strong>1.3.First, we tested thermal pain sensitivities to implicate a possible role of TRPV1 and TRPM8 in DPN. Paw withdrawal latency on a hot plate test was decreased, and acetone-induced cold sensitivity was enhanced in diabetic mice as compared to non-diabetic mice. Dorsal Root Ganglion (DRG) neurons dissociated from diabetic hyperalgesic mice exhibited an increase in TRPV1-mediated current and a decrease in TRPM8-mediated currents as compared to non-diabetic mice. Then, we determined the modulation of TRPV1- and TRPM8-mediated currents using HEK cells heterologously expressing TRPV1 by promoting PKC- and PKA-mediated phosphorylation. Both Phorbol 12,13-Dibutyrate (PDBu), a PKC activator and forskolin, a PKA activator upregulated TRPV1-mediated currents but downregulated TRPM8-mediated currents. In diabetic mice, intraplantar injection of capsaicin, a TRPV1 agonist-induced nocifensive behavior but the severity of this behavior was significantly lower when co-administered with menthol, a TRPM8 agonist.</p><p><strong>Conclusions: </strong>1.4.These findings suggest that diabetic thermal hyperalgesia mediated by up-regulation of TRPV1 function may be further aggravated by the downregulation of TRPM8 function. Targeting TRPV1 may be a useful approach to alleviate pain associated with DPN.</p>\",\"PeriodicalId\":73707,\"journal\":{\"name\":\"Journal of diabetes and treatment\",\"volume\":\"2017 4\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2017-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317870/pdf/nihms-1002094.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of diabetes and treatment\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2017/10/17 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of diabetes and treatment","FirstCategoryId":"1085","ListUrlMain":"","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2017/10/17 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

摘要

摘要目的:1.1。瞬时受体电位(Vanilloid 1) TRPV1和(Melastatin 8) TRPM8分别是热感知和冷感知的非选择性阳离子通道。我们试图将糖尿病周围神经病变(DPN)中TRPV1-和trpm8介导的膜电流调节与热敏性改变联系起来。方法:1.2。采用链脲佐菌素(STZ)诱导的糖尿病小鼠,分别采用热板法和丙酮跌落法测定热(热、冷)痛敏感性。膜片钳技术记录膜电流。结果:1.3。首先,我们测试了热痛敏感性,以暗示TRPV1和TRPM8在DPN中的可能作用。与非糖尿病小鼠相比,糖尿病小鼠在热板实验中爪子戒断潜伏期降低,丙酮诱导的冷敏感性增强。与非糖尿病小鼠相比,糖尿病高痛觉小鼠背根神经节(DRG)分离的神经元表现出trpv1介导的电流增加和trpm8介导的电流减少。然后,我们利用HEK细胞异种表达TRPV1,通过促进PKC和pka介导的磷酸化,确定了TRPV1和trpm8介导的电流的调节。PKC激活剂Phorbol 12,13- dibutyrate (PDBu)和PKA激活剂forskolin均上调trpv1介导的电流,但下调trpm8介导的电流。在糖尿病小鼠中,足底注射辣椒素(一种TRPV1激动剂)诱导了不良行为,但与薄荷醇(一种TRPM8激动剂)联合使用时,这种行为的严重程度显著降低。结论:1.4。这些发现提示,TRPV1功能上调介导的糖尿病热痛觉过敏可能会因TRPM8功能下调而进一步加重。靶向TRPV1可能是缓解DPN相关疼痛的有效方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Role of Transient Receptor Potential Channels Trpv1 and Trpm8 in Diabetic Peripheral Neuropathy.

Role of Transient Receptor Potential Channels Trpv1 and Trpm8 in Diabetic Peripheral Neuropathy.

Role of Transient Receptor Potential Channels Trpv1 and Trpm8 in Diabetic Peripheral Neuropathy.

Role of Transient Receptor Potential Channels Trpv1 and Trpm8 in Diabetic Peripheral Neuropathy.

Objective: 1.1.Transient Receptor Potential (Vanilloid 1) TRPV1 and (Melastatin 8) TRPM8 are heat and cold sensing non-selective cation channels, respectively. We sought to correlate the modulation of TRPV1- and TRPM8-mediated membrane currents and altered thermal sensitivity in Diabetic Peripheral Neuropathy (DPN).

Method: 1.2.Streptozotocin (STZ)-induced diabetic mice were used and thermal (heat and cold) pain sensitivities were determined using hot plate and acetone drop test, respectively. Membrane currents were recorded using patch-clamp techniques.

Results: 1.3.First, we tested thermal pain sensitivities to implicate a possible role of TRPV1 and TRPM8 in DPN. Paw withdrawal latency on a hot plate test was decreased, and acetone-induced cold sensitivity was enhanced in diabetic mice as compared to non-diabetic mice. Dorsal Root Ganglion (DRG) neurons dissociated from diabetic hyperalgesic mice exhibited an increase in TRPV1-mediated current and a decrease in TRPM8-mediated currents as compared to non-diabetic mice. Then, we determined the modulation of TRPV1- and TRPM8-mediated currents using HEK cells heterologously expressing TRPV1 by promoting PKC- and PKA-mediated phosphorylation. Both Phorbol 12,13-Dibutyrate (PDBu), a PKC activator and forskolin, a PKA activator upregulated TRPV1-mediated currents but downregulated TRPM8-mediated currents. In diabetic mice, intraplantar injection of capsaicin, a TRPV1 agonist-induced nocifensive behavior but the severity of this behavior was significantly lower when co-administered with menthol, a TRPM8 agonist.

Conclusions: 1.4.These findings suggest that diabetic thermal hyperalgesia mediated by up-regulation of TRPV1 function may be further aggravated by the downregulation of TRPM8 function. Targeting TRPV1 may be a useful approach to alleviate pain associated with DPN.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信