Hyperalgesia and Allodynia Elicited by Histamine and Non-histaminergic Itch Mediators.

What is it about?

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, but not the TRPA1 antagonist HC-030031, 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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Why is it important?

TRPV1 and TRPA1 channel inhibitors may have potential use in reducing hyperalgesia and allodynia associated with histaminergic and non-histaminergic itch, respectively. Thus, this study is important to determine if the chronic itch is also associated with painful dysesthesias. One implication of these findings is that TRP channel antagonists might prove to be useful in the clinical treatment of increased pain and allodynia that may be symptoms in patients suffering from chronic itch.

Perspectives