Thermal Hyperalgesia and Mechanical Allodynia Elicited by Histamine and Non-histaminergic Itch Mediators: Respective Involvement of TRPV1 and TRPA1.
Thermal Hyperalgesia and Mechanical Allodynia Elicited by Histamine and Non-histaminergic Itch Mediators: Respective Involvement of TRPV1 and TRPA1.
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由组胺和非希斯明素能瘙痒介质引起的热痛觉过敏和机械性异常性症：TRPV1和TRPA1的各自参与。
DOI：
10.1016/j.neuroscience.2020.09.048
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发表时间：
2020-11-21
期刊：
影响因子：
3.3
通讯作者：
Carstens E
中科院分区：
文献类型：
--
作者：
Tsagareli MG;Nozadze I;Tsiklauri N;Carstens MI;Gurtskaia G;Carstens E
急性瘙痒由组胺以及非组胺能瘙痒介质（包括氯喹、BAM 8 -22和Ser-Leu-Ile-Gly-Arg-Leu（SLIGRL））引起。当皮内注射时，组胺与组胺H1和H4受体结合，组胺H1和H4受体激活瞬时受体电位香草酸1（TRPV 1），使其成为去乙酰化受体。氯喹、BAM 8 -22和SLIGRL分别与Mas相关的G蛋白偶联受体MrgprA 3、MrgprC 11和MrgprC 11/PAR 2结合，进而激活瞬时受体电位锚蛋白1（TRPA 1）。在这项研究中，我们测试了组胺、氯喹、BAM 8 -22和SLIGRL是否会引起成年雄性小鼠的热痛觉过敏和机械性异常性疼痛。我们测量了从有害的热刺激后爪回缩的潜伏期，以及从von Frey机械刺激后爪回缩的阈值。足底注射组胺可引起明显的热痛觉过敏（p < 0.001）和机械性痛觉超敏（p < 0.001），并持续1 h。用TRPV 1拮抗剂AMG-517（10或20 μg）预处理，而不是TRPA 1拮抗剂HC-030031（50或100 μg），可显著减弱组胺引起的热痛觉过敏和机械性异常性疼痛的幅度和时间进程（两者均为p < 0.001），表明这些作用由TRPV 1介导。相比之下，用TRPA 1拮抗剂预处理显著降低由氯喹（两者均为p < 0.001）、BAM-822（分别为p <0.01，p < 0.001）和SLGRL（分别为p < 0.05，p < 0.001）引起的热痛觉过敏和机械性异常性疼痛，表明由这些非组胺能瘙痒介质引起的作用需要TRPA 1。因此，TRPV 1和TRPA 1通道抑制剂可能分别在减少与组胺能和非组胺能瘙痒相关的痛觉过敏和异常性疼痛中具有潜在的用途。
Acute itch is elicited by histamine, as well as non-histaminergic itch mediators including chloroquine, BAM8–22 and Ser-Leu-Ile-Gly-Arg-Leu (SLIGRL). When injected intradermally, histamine binds to histamine H1 and H4 receptors that activate transient receptor potential vanilloid 1 (TRPV1) to depolarize pruriceptors. Chloroquine, BAM8–22, and SLIGRL, respectively, bind to Mas-related G-protein-coupled receptors MrgprA3, MrgprC11, and MrgprC11/PAR2 that in turn activate transient receptor potential ankyrin 1 (TRPA1). In this study we tested if histamine, chloroquine, BAM8–22 and SLIGRL elicit thermal hyperalgesia and mechanical allodynia in adult male mice. We measured the latency of hindpaw withdrawal from a noxious heat stimulus, and the threshold for hindpaw withdrawal from a von Frey mechanical stimulus. Intraplantar injection of histamine resulted in significant thermal hyperalgesia (p < 0.001) and mechanical allodynia (p < 0.001) ipsilaterally that persisted for 1 h. Pretreatment with the TRPV1 antagonist AMG-517 (10 or 20 μg), but not the TRPA1 antagonist HC-030031 (50 or 100 μg), significantly attenuated the magnitude and time course of thermal hyperalgesia and mechanical allodynia elicited by histamine (p < 0.001 for both), indicating that these effects are mediated by TRPV1. In contrast, pretreatment with the TRPA1 antagonist significantly reduced thermal hyperalgesia and mechanical allodynia elicited by chloroquine (p < 0.001 for both), BAM-822 (p < 0.01, p < 0.001, respectively) and SLGRL (p < 0.05, p < 0.001, respectively), indicating that effects elicited by these non-histaminergic itch mediators require TRPA1. TRPV1 and TRPA1 channel inhibitors thus may have potential use in reducing hyperalgesia and allodynia associated with histaminergic and non-histaminergic itch, respectively.
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影响因子：
25
作者：
Han, Liang;Ma, Chao;Liu, Qin;Weng, Hao-Jui;Cui, Yiyuan;Tang, Zongxiang;Kim, Yushin;Nie, Hong;Qu, Lintao;Patel, Kush N.;Li, Zhe;McNeil, Benjamin;He, Shaoqiu;Guan, Yun;Xiao, Bo;LaMotte, Robert H.;Dong, Xinzhong
通讯作者：
Dong, Xinzhong
影响因子：
3.3
作者：
Akiyama, T.;Tominaga, M.;Davoodi, A.;Nagamine, M.;Blansit, K.;Horwitz, A.;Carstens, M. I.;Carstens, E.
通讯作者：
Carstens, E.
影响因子：
2.5
作者：
Follansbee, T.;Akiyama, G. T.;Carstens, E.
通讯作者：
Carstens, E.
DOI：
10.1523/jneurosci.1760-08.2008
发表时间：
2008-07-23
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Johanek LM;Meyer RA;Friedman RM;Greenquist KW;Shim B;Borzan J;Hartke T;LaMotte RH;Ringkamp M
通讯作者：
Ringkamp M
影响因子：
2.5
作者：
Klein, Amanda;Carstens, Mirela Iodi;Carstens, E.
通讯作者：
Carstens, E.