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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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Related in: MedlinePlus

Pirt is not involved in all types of itch.(A, B) Pirt WT (n = 10) and KO (n = 8) mice display comparable formalin-induced (5%) itch behavior. (C) Ca2+ responses to formalin (0.02%) are unaltered in Pirt mutant DRG neurons (n = 6 per genotype). (D) Saline vehicle induces a similar baseline, i.e. spontaneous, scratching response in Pirt−/− (n = 5) and WT (n = 7) mice.
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pone-0020559-g005: Pirt is not involved in all types of itch.(A, B) Pirt WT (n = 10) and KO (n = 8) mice display comparable formalin-induced (5%) itch behavior. (C) Ca2+ responses to formalin (0.02%) are unaltered in Pirt mutant DRG neurons (n = 6 per genotype). (D) Saline vehicle induces a similar baseline, i.e. spontaneous, scratching response in Pirt−/− (n = 5) and WT (n = 7) mice.

Mentions: These results lead to the question of how broadly Pirt functions in itch and whether it is involved in all types of pruritoception. We tested another compound, formalin, which has long been used to model pain responses [41] although recent evidence suggests its acute effect may be pruritogenic [42], [43]. Interestingly, Pirt mice show scratching responses that do not differ significantly from WT controls (429 bouts in WT vs. 367 in KO, Fig. 5A, B). Formalin is known to directly activate the TRPA1 channel, which is also required for the compound's pain behavior [44], [45]. Earlier work suggests Pirt is not involved in TRPA1-dependent physiological or behavioral, i.e. formalin-induced pain, responses [3]. Consistent with these findings, we found Pirt−/− DRG neurons display Ca2+ responses to formalin that are indistinguishable from WT neurons (17.2% of WT neurons vs. 17.4% of KO, Fig. 5C), a response that is known to require TRPA1 [45]. This shows Pirt is not compulsory for all varieties of itch and reveals a degree of specificity in its function.


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 is not involved in all types of itch.(A, B) Pirt WT (n = 10) and KO (n = 8) mice display comparable formalin-induced (5%) itch behavior. (C) Ca2+ responses to formalin (0.02%) are unaltered in Pirt mutant DRG neurons (n = 6 per genotype). (D) Saline vehicle induces a similar baseline, i.e. spontaneous, scratching response in Pirt−/− (n = 5) and WT (n = 7) mice.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3105090&req=5

pone-0020559-g005: Pirt is not involved in all types of itch.(A, B) Pirt WT (n = 10) and KO (n = 8) mice display comparable formalin-induced (5%) itch behavior. (C) Ca2+ responses to formalin (0.02%) are unaltered in Pirt mutant DRG neurons (n = 6 per genotype). (D) Saline vehicle induces a similar baseline, i.e. spontaneous, scratching response in Pirt−/− (n = 5) and WT (n = 7) mice.
Mentions: These results lead to the question of how broadly Pirt functions in itch and whether it is involved in all types of pruritoception. We tested another compound, formalin, which has long been used to model pain responses [41] although recent evidence suggests its acute effect may be pruritogenic [42], [43]. Interestingly, Pirt mice show scratching responses that do not differ significantly from WT controls (429 bouts in WT vs. 367 in KO, Fig. 5A, B). Formalin is known to directly activate the TRPA1 channel, which is also required for the compound's pain behavior [44], [45]. Earlier work suggests Pirt is not involved in TRPA1-dependent physiological or behavioral, i.e. formalin-induced pain, responses [3]. Consistent with these findings, we found Pirt−/− DRG neurons display Ca2+ responses to formalin that are indistinguishable from WT neurons (17.2% of WT neurons vs. 17.4% of KO, Fig. 5C), a response that is known to require TRPA1 [45]. This shows Pirt is not compulsory for all varieties of itch and reveals a degree of specificity in its function.

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