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Cinnamaldehyde elicits itch behavior via TRPV1 and TRPV4 but not TRPA1

INTRODUCTION: Cinnamaldehyde (CA) elicits itch sensation in humans. We investigated if CA elicits scratching behavior in mice and determined the roles for TRPV1, TRPA1, and TRPV4. MATERIALS AND METHODS: Scratching behavior elicited by intradermal injection of CA was assessed in wildtype (WT) mice an...

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Autores principales: Domocos, Dan, Follansbee, Taylor, Nguyen, Amanda, Nguyen, Tony, Carstens, Mirela I., Carstens, Earl
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8388579/
https://www.ncbi.nlm.nih.gov/pubmed/34458578
http://dx.doi.org/10.1097/itx.0000000000000036
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author Domocos, Dan
Follansbee, Taylor
Nguyen, Amanda
Nguyen, Tony
Carstens, Mirela I.
Carstens, Earl
author_facet Domocos, Dan
Follansbee, Taylor
Nguyen, Amanda
Nguyen, Tony
Carstens, Mirela I.
Carstens, Earl
author_sort Domocos, Dan
collection PubMed
description INTRODUCTION: Cinnamaldehyde (CA) elicits itch sensation in humans. We investigated if CA elicits scratching behavior in mice and determined the roles for TRPV1, TRPA1, and TRPV4. MATERIALS AND METHODS: Scratching behavior elicited by intradermal injection of CA was assessed in wildtype (WT) mice and knockout (KO) mice lacking TRPV1, TRPA1, TRPV4, or deficient in mast cells. We also assessed scratching and wet dog shakes elicited by low-threshold mechanical stimulation of skin treated topically with CA or vehicle. Using calcium imaging we tested if CA activates dorsal root ganglion (DRG) neurons of each genotype. RESULTS: Intradermal cheek injection of CA elicited dose-dependent hindlimb scratch bouts, with fewer forelimb wipes and facial groom bouts that were not dose-dependent. CA elicited significantly fewer scratch bouts in TRPV1 and TRPV4 KO mice, but not TRPA1KOs, compared with WTs. There were no sex differences across genotypes. The histamine H1 antagonist cetirizine did not affect CA-evoked scratching, which was normal in mast cell deficient mice, indicating lack of histamine involvement. Scores for alloknesis were significantly greater following topical application of CA compared with vehicle. Post-CA alloknesis scores were significantly higher in TRPV4KOs of both sexes and in female TRPV1 and TRPA1KOs, compared with WTs. Low threshold mechanical stimuli also elicited significantly more wet dog shakes in mice treated topically with 20% CA, with significantly fewer in TRPV1, TRPA1, and TRPV4KOs compared with WTs. In calcium imaging studies, CA excited 24% of WT DRG cells, significantly fewer (11.5%) in cells from TRPV4KOs, and none in TRPA1KOs. Responses of cells of all genotypes exhibited significant sensitization to repeated CA stimulation. Sensitization was significantly enhanced by IL-4, which itself excited 16% of WT DRG cells and none from TRPA1KOs. DISCUSSION: The results indicate that TRPA1 is dispensable for CA-evoked scratching, which depends partly on TRPV1 and TRPV4.
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spelling pubmed-83885792021-08-26 Cinnamaldehyde elicits itch behavior via TRPV1 and TRPV4 but not TRPA1 Domocos, Dan Follansbee, Taylor Nguyen, Amanda Nguyen, Tony Carstens, Mirela I. Carstens, Earl Itch (Phila) Article INTRODUCTION: Cinnamaldehyde (CA) elicits itch sensation in humans. We investigated if CA elicits scratching behavior in mice and determined the roles for TRPV1, TRPA1, and TRPV4. MATERIALS AND METHODS: Scratching behavior elicited by intradermal injection of CA was assessed in wildtype (WT) mice and knockout (KO) mice lacking TRPV1, TRPA1, TRPV4, or deficient in mast cells. We also assessed scratching and wet dog shakes elicited by low-threshold mechanical stimulation of skin treated topically with CA or vehicle. Using calcium imaging we tested if CA activates dorsal root ganglion (DRG) neurons of each genotype. RESULTS: Intradermal cheek injection of CA elicited dose-dependent hindlimb scratch bouts, with fewer forelimb wipes and facial groom bouts that were not dose-dependent. CA elicited significantly fewer scratch bouts in TRPV1 and TRPV4 KO mice, but not TRPA1KOs, compared with WTs. There were no sex differences across genotypes. The histamine H1 antagonist cetirizine did not affect CA-evoked scratching, which was normal in mast cell deficient mice, indicating lack of histamine involvement. Scores for alloknesis were significantly greater following topical application of CA compared with vehicle. Post-CA alloknesis scores were significantly higher in TRPV4KOs of both sexes and in female TRPV1 and TRPA1KOs, compared with WTs. Low threshold mechanical stimuli also elicited significantly more wet dog shakes in mice treated topically with 20% CA, with significantly fewer in TRPV1, TRPA1, and TRPV4KOs compared with WTs. In calcium imaging studies, CA excited 24% of WT DRG cells, significantly fewer (11.5%) in cells from TRPV4KOs, and none in TRPA1KOs. Responses of cells of all genotypes exhibited significant sensitization to repeated CA stimulation. Sensitization was significantly enhanced by IL-4, which itself excited 16% of WT DRG cells and none from TRPA1KOs. DISCUSSION: The results indicate that TRPA1 is dispensable for CA-evoked scratching, which depends partly on TRPV1 and TRPV4. 2020-07-24 2020 /pmc/articles/PMC8388579/ /pubmed/34458578 http://dx.doi.org/10.1097/itx.0000000000000036 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Article
Domocos, Dan
Follansbee, Taylor
Nguyen, Amanda
Nguyen, Tony
Carstens, Mirela I.
Carstens, Earl
Cinnamaldehyde elicits itch behavior via TRPV1 and TRPV4 but not TRPA1
title Cinnamaldehyde elicits itch behavior via TRPV1 and TRPV4 but not TRPA1
title_full Cinnamaldehyde elicits itch behavior via TRPV1 and TRPV4 but not TRPA1
title_fullStr Cinnamaldehyde elicits itch behavior via TRPV1 and TRPV4 but not TRPA1
title_full_unstemmed Cinnamaldehyde elicits itch behavior via TRPV1 and TRPV4 but not TRPA1
title_short Cinnamaldehyde elicits itch behavior via TRPV1 and TRPV4 but not TRPA1
title_sort cinnamaldehyde elicits itch behavior via trpv1 and trpv4 but not trpa1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8388579/
https://www.ncbi.nlm.nih.gov/pubmed/34458578
http://dx.doi.org/10.1097/itx.0000000000000036
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