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Alleviation of behavioral hypersensitivity in mouse models of inflammatory pain with two structurally different casein kinase 1 (CK1) inhibitors

BACKGROUND: The phylogenetically highly conserved CK1 protein kinases consisting of at least seven isoforms form a distinct family within the eukaryotic protein kinases. CK1 family members play crucial roles in a wide range of signaling activities. However, the functional role of CK1 in somatosensor...

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Autores principales: Kurihara, Takashi, Sakurai, Eri, Toyomoto, Masayasu, Kii, Isao, Kawamoto, Daisuke, Asada, Toshihide, Tanabe, Tsutomu, Yoshimura, Megumu, Hagiwara, Masatoshi, Miyata, Atsuro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4008364/
https://www.ncbi.nlm.nih.gov/pubmed/24612480
http://dx.doi.org/10.1186/1744-8069-10-17
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author Kurihara, Takashi
Sakurai, Eri
Toyomoto, Masayasu
Kii, Isao
Kawamoto, Daisuke
Asada, Toshihide
Tanabe, Tsutomu
Yoshimura, Megumu
Hagiwara, Masatoshi
Miyata, Atsuro
author_facet Kurihara, Takashi
Sakurai, Eri
Toyomoto, Masayasu
Kii, Isao
Kawamoto, Daisuke
Asada, Toshihide
Tanabe, Tsutomu
Yoshimura, Megumu
Hagiwara, Masatoshi
Miyata, Atsuro
author_sort Kurihara, Takashi
collection PubMed
description BACKGROUND: The phylogenetically highly conserved CK1 protein kinases consisting of at least seven isoforms form a distinct family within the eukaryotic protein kinases. CK1 family members play crucial roles in a wide range of signaling activities. However, the functional role of CK1 in somatosensory pain signaling has not yet been fully understood. The aim of this study was to clarify the role of CK1 in the regulation of inflammatory pain in mouse carrageenan and complete Freund’s adjuvant (CFA) models. RESULTS: We have used two structurally different CK1 inhibitors, TG003 and IC261. TG003, which was originally identified as a cdc2-like kinase inhibitor, had potent inhibitory effects on CK1 isoforms in vitro and in cultured cells. Intrathecal injection of either TG003 (1-100 pmol) or IC261 (0.1-1 nmol) dose-dependently decreased mechanical allodynia and thermal hyperalgesia induced by carrageenan or CFA. Bath-application of either TG003 (1 μM) or IC261 (1 μM) had only marginal effects on spontaneous excitatory postsynaptic currents (sEPSCs) recorded in the substantia gelatinosa neurons of control mice. However, both compounds decreased the frequency of sEPSCs in both inflammatory pain models. CONCLUSIONS: These results suggest that CK1 plays an important pathophysiological role in spinal inflammatory pain transmission, and that inhibition of the CK1 activity may provide a novel strategy for the treatment of inflammatory pain.
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spelling pubmed-40083642014-05-03 Alleviation of behavioral hypersensitivity in mouse models of inflammatory pain with two structurally different casein kinase 1 (CK1) inhibitors Kurihara, Takashi Sakurai, Eri Toyomoto, Masayasu Kii, Isao Kawamoto, Daisuke Asada, Toshihide Tanabe, Tsutomu Yoshimura, Megumu Hagiwara, Masatoshi Miyata, Atsuro Mol Pain Research BACKGROUND: The phylogenetically highly conserved CK1 protein kinases consisting of at least seven isoforms form a distinct family within the eukaryotic protein kinases. CK1 family members play crucial roles in a wide range of signaling activities. However, the functional role of CK1 in somatosensory pain signaling has not yet been fully understood. The aim of this study was to clarify the role of CK1 in the regulation of inflammatory pain in mouse carrageenan and complete Freund’s adjuvant (CFA) models. RESULTS: We have used two structurally different CK1 inhibitors, TG003 and IC261. TG003, which was originally identified as a cdc2-like kinase inhibitor, had potent inhibitory effects on CK1 isoforms in vitro and in cultured cells. Intrathecal injection of either TG003 (1-100 pmol) or IC261 (0.1-1 nmol) dose-dependently decreased mechanical allodynia and thermal hyperalgesia induced by carrageenan or CFA. Bath-application of either TG003 (1 μM) or IC261 (1 μM) had only marginal effects on spontaneous excitatory postsynaptic currents (sEPSCs) recorded in the substantia gelatinosa neurons of control mice. However, both compounds decreased the frequency of sEPSCs in both inflammatory pain models. CONCLUSIONS: These results suggest that CK1 plays an important pathophysiological role in spinal inflammatory pain transmission, and that inhibition of the CK1 activity may provide a novel strategy for the treatment of inflammatory pain. BioMed Central 2014-03-10 /pmc/articles/PMC4008364/ /pubmed/24612480 http://dx.doi.org/10.1186/1744-8069-10-17 Text en Copyright © 2014 Kurihara et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Kurihara, Takashi
Sakurai, Eri
Toyomoto, Masayasu
Kii, Isao
Kawamoto, Daisuke
Asada, Toshihide
Tanabe, Tsutomu
Yoshimura, Megumu
Hagiwara, Masatoshi
Miyata, Atsuro
Alleviation of behavioral hypersensitivity in mouse models of inflammatory pain with two structurally different casein kinase 1 (CK1) inhibitors
title Alleviation of behavioral hypersensitivity in mouse models of inflammatory pain with two structurally different casein kinase 1 (CK1) inhibitors
title_full Alleviation of behavioral hypersensitivity in mouse models of inflammatory pain with two structurally different casein kinase 1 (CK1) inhibitors
title_fullStr Alleviation of behavioral hypersensitivity in mouse models of inflammatory pain with two structurally different casein kinase 1 (CK1) inhibitors
title_full_unstemmed Alleviation of behavioral hypersensitivity in mouse models of inflammatory pain with two structurally different casein kinase 1 (CK1) inhibitors
title_short Alleviation of behavioral hypersensitivity in mouse models of inflammatory pain with two structurally different casein kinase 1 (CK1) inhibitors
title_sort alleviation of behavioral hypersensitivity in mouse models of inflammatory pain with two structurally different casein kinase 1 (ck1) inhibitors
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4008364/
https://www.ncbi.nlm.nih.gov/pubmed/24612480
http://dx.doi.org/10.1186/1744-8069-10-17
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