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Pirt, a TRPV1 modulator, is required for histamine-dependent and -independent itch.

Patel KN, Liu Q, Meeker S, Undem BJ, Dong X - PLoS ONE (2011)

Bottom Line: Itch, or pruritus, is an important clinical problem whose molecular basis has yet to be understood.Here we show that Pirt, known to play a vital part in sensing pain through modulation of the transient receptor potential vanilloid 1 (TRPV1) channel, is also necessary for proper itch sensation.Our findings demonstrate that the function of Pirt extends beyond nociception via TRPV1 regulation to its role as a critical component in several itch signaling pathways.

View Article: PubMed Central - PubMed

Affiliation: The Solomon H. Snyder Department of Neuroscience, Center for Sensory Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.

ABSTRACT
Itch, or pruritus, is an important clinical problem whose molecular basis has yet to be understood. Recent work has begun to identify genes that contribute to detecting itch at the molecular level. Here we show that Pirt, known to play a vital part in sensing pain through modulation of the transient receptor potential vanilloid 1 (TRPV1) channel, is also necessary for proper itch sensation. Pirt(-/-) mice exhibit deficits in cellular and behavioral responses to various itch-inducing compounds, or pruritogens. Pirt contributes to both histaminergic and nonhistaminergic itch and, crucially, is involved in forms of itch that are both TRPV1-dependent and -independent. Our findings demonstrate that the function of Pirt extends beyond nociception via TRPV1 regulation to its role as a critical component in several itch signaling pathways.

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Pirt plays a role in mast cell-dependent itch.(A, B) In an allergy model, ovalbumin (50 µg) induces less scratching in Pirt−/− (n = 11) and SASH (n = 7) mice compared to WT controls (n = 8). (C, D) Pirt KO mice (n = 11) show a trend toward decreased scratching compared to WT (n = 13) when injected with compound 48/80 (30 µg), but this difference just misses statistical significance (p<0.06). * p<0.05, **** p<0.00001; two-tailed unpaired t-test.
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pone-0020559-g004: Pirt plays a role in mast cell-dependent itch.(A, B) In an allergy model, ovalbumin (50 µg) induces less scratching in Pirt−/− (n = 11) and SASH (n = 7) mice compared to WT controls (n = 8). (C, D) Pirt KO mice (n = 11) show a trend toward decreased scratching compared to WT (n = 13) when injected with compound 48/80 (30 µg), but this difference just misses statistical significance (p<0.06). * p<0.05, **** p<0.00001; two-tailed unpaired t-test.

Mentions: One allergy model of itch makes use of the egg protein ovalbumin, an otherwise innocuous molecule that induces an immune response when co-injected with an adjuvant; subsequent injection of ovalbumin alone causes scratching [38]. We tested Pirt KO mice in this allergy model and found they exhibit significantly less scratching compared to WT (154 bouts vs. 115 bouts in KO, Fig. 4A, B). As mast cells are thought to play a critical role in the allergy response, we also tested SASH mice, which lack mast cells due to a chromosomal inversion affecting c-kit gene function [39]. They show drastically reduced scratching (30 bouts) in response to ovalbumin injection, verifying the role of mast cells in allergy-associated itch.


Pirt, a TRPV1 modulator, is required for histamine-dependent and -independent itch.

Patel KN, Liu Q, Meeker S, Undem BJ, Dong X - PLoS ONE (2011)

Pirt plays a role in mast cell-dependent itch.(A, B) In an allergy model, ovalbumin (50 µg) induces less scratching in Pirt−/− (n = 11) and SASH (n = 7) mice compared to WT controls (n = 8). (C, D) Pirt KO mice (n = 11) show a trend toward decreased scratching compared to WT (n = 13) when injected with compound 48/80 (30 µg), but this difference just misses statistical significance (p<0.06). * p<0.05, **** p<0.00001; two-tailed unpaired t-test.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3105090&req=5

pone-0020559-g004: Pirt plays a role in mast cell-dependent itch.(A, B) In an allergy model, ovalbumin (50 µg) induces less scratching in Pirt−/− (n = 11) and SASH (n = 7) mice compared to WT controls (n = 8). (C, D) Pirt KO mice (n = 11) show a trend toward decreased scratching compared to WT (n = 13) when injected with compound 48/80 (30 µg), but this difference just misses statistical significance (p<0.06). * p<0.05, **** p<0.00001; two-tailed unpaired t-test.
Mentions: One allergy model of itch makes use of the egg protein ovalbumin, an otherwise innocuous molecule that induces an immune response when co-injected with an adjuvant; subsequent injection of ovalbumin alone causes scratching [38]. We tested Pirt KO mice in this allergy model and found they exhibit significantly less scratching compared to WT (154 bouts vs. 115 bouts in KO, Fig. 4A, B). As mast cells are thought to play a critical role in the allergy response, we also tested SASH mice, which lack mast cells due to a chromosomal inversion affecting c-kit gene function [39]. They show drastically reduced scratching (30 bouts) in response to ovalbumin injection, verifying the role of mast cells in allergy-associated itch.

Bottom Line: Itch, or pruritus, is an important clinical problem whose molecular basis has yet to be understood.Here we show that Pirt, known to play a vital part in sensing pain through modulation of the transient receptor potential vanilloid 1 (TRPV1) channel, is also necessary for proper itch sensation.Our findings demonstrate that the function of Pirt extends beyond nociception via TRPV1 regulation to its role as a critical component in several itch signaling pathways.

View Article: PubMed Central - PubMed

Affiliation: The Solomon H. Snyder Department of Neuroscience, Center for Sensory Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.

ABSTRACT
Itch, or pruritus, is an important clinical problem whose molecular basis has yet to be understood. Recent work has begun to identify genes that contribute to detecting itch at the molecular level. Here we show that Pirt, known to play a vital part in sensing pain through modulation of the transient receptor potential vanilloid 1 (TRPV1) channel, is also necessary for proper itch sensation. Pirt(-/-) mice exhibit deficits in cellular and behavioral responses to various itch-inducing compounds, or pruritogens. Pirt contributes to both histaminergic and nonhistaminergic itch and, crucially, is involved in forms of itch that are both TRPV1-dependent and -independent. Our findings demonstrate that the function of Pirt extends beyond nociception via TRPV1 regulation to its role as a critical component in several itch signaling pathways.

Show MeSH
Related in: MedlinePlus