Thermal Hyperalgesia and Mechanical Allodynia Elicited by Histamine and Non-histaminergic Itch Mediators: Respective Involvement of TRPV1 and TRPA1.
Autor: | Tsagareli MG; Beritashvili Center for Experimental Biomedicine, Tbilisi, Georgia. Electronic address: m.tsagareli@biomedicine.org.ge., Nozadze I; Beritashvili Center for Experimental Biomedicine, Tbilisi, Georgia., Tsiklauri N; Beritashvili Center for Experimental Biomedicine, Tbilisi, Georgia., Carstens MI; University of California, Davis, CA, USA., Gurtskaia G; Beritashvili Center for Experimental Biomedicine, Tbilisi, Georgia., Carstens E; University of California, Davis, CA, USA. Electronic address: eecarstens@ucdavis.edu. |
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Jazyk: | angličtina |
Zdroj: | Neuroscience [Neuroscience] 2020 Nov 21; Vol. 449, pp. 35-45. Date of Electronic Publication: 2020 Oct 01. |
DOI: | 10.1016/j.neuroscience.2020.09.048 |
Abstrakt: | 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. (Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.) |
Databáze: | MEDLINE |
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