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Papers of the Week

Papers: 3 Oct 2020 - 9 Oct 2020

Animal Studies


2020 Sep 30


Thermal hyperalgesia and mechanical allodynia elicited by histamine and non-histaminergic itch mediators: Respective involvement of TRPV1 and TRPA1.


Tsagareli MG, Nozadze I, Tsiklauri N, Iodi Carstens M, Gurtskaia G, Carstens E
Neuroscience. 2020 Sep 30.
PMID: 33010342.


Acute itch is elicited by histamine, as well as non-histaminergic itch mediators including chloroquine, BAM8-22 and SLIGRL. When injected intradermally, histamine binds to histamine H1 and H4 receptors that activate TRPV1 to depolarize pruriceptors. Chloroquine, BAM-822, and SLIGRL respectively bind to Mas-related G-protein-coupled receptors MrgprA3, MrgprC11, and MrgprC11/PAR2 that in turn activate 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<0.01) and mechanical allodynia (p<0.0001) ipsilaterally that persisted for 1 hr. 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<0.0001 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 and, p<0.0001, respectively), 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.