2007 Fiscal Year Final Research Report Summary
Roles of spinal astrocyte in the induction and maintenance of chronic pain
| Project/Area Number |
18613006
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pain science
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| Research Institution | Kyoto University |
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Principal Investigator |
NAKAGAWA Takayuki Kyoto University, Graduate School of Pharmaceutical Sciences, Associate Professor (30303845)
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| Co-Investigator(Kenkyū-buntansha) |
MINAMI Masabumi Hokkaido University, Graduate School of Pharmaceutical Sciences, Professor (20243040)
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| Project Period (FY) |
2006 – 2007
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| Keywords | chronic pain / astrocyte / ATP / MAPK / glial glutamate transporter / GLT-1 / trafficking / spinal cord |
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| Research Abstract |
We have investigated the roles of spinal astrocytes in chronic pain. Intrathecal administration of ATP to rats produced short-lasting hyperalgesia (<20 min) and subsequently long-lasting allodynia, which appeared within 5 min, reached a plateau between 15 and 30min and lasted fm 3-4 weeks. In the spinal cord, intrathecal ATP administration caused microglia activation within 1 day (induction phase) and subsequently astrocytic activation, which peaked at 1-3 days (transition and early maintenance phase). Taken together with further behavioral studies using inhibitors for microglial and astrocytic activation, and MAPK inhibitors, it is suggested that early microglia activation contributes to the initial induction of chronic pain and precipitates, in turn, the subsequent and sustained astrocytic activation, which is implicated in the transition and maintenance of the persistent pain state.
In the inflammatory (carrageenan/kaolin) and neuropathic pain (partial sciatic nerve ligation (pSNL))
… More
rat models, the total expression or membrane localization of a glial glutamate transporter GLT-1, which is mainly expressed in astrocytes, in the spinal cord was decreased. Gene transfer of GLT-1 into the spinal cord by the recombinant adenoviruses reduced the induction of inflammatory mechanical hyperalgesia and pSNL-induced allodynia (neuropathic pain), although it had no effect in acute mechanical and thermal pain. These results suggest that dysfunction of GLT-1 by decreased expression of intracellular trafficking in astrocytes contributes to the induction of chronic pain.
Finally, to elucidate the molecular mechanisms underlying GLT-1 trafficking in astrocyte, we constructed a recombinant adenovirus expressing EGFP-tagged GLT-1 and analyzed time-lapse imaging of GLT-1 dynamics in live astrocytes. In rat astroglia-neuronal mixed cultures, treatment with glutamate rapidly induced formation of clusters and intracellular trafficking of GLT-1 via endocytotic pathways. Furthermore, our results suggest that Na^+ influx associated with substrate-transport via GLT-1, but not stimulation of glutamate receptors and intracellular Ca^<2+> signaling, triggers the GLT-1 clustering. Less
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[Journal Article] Characterization of the tritium-labeled analog of L-threo-β-benzyloxyaspartate binding to glutamate transporters2007
Author(s)
Shimamoto, K., Otsubo, Y., Shigeri, Y., Yasuda-Kamatani, Y., Satoh, M., Kaneko, S., Nakagawa, T
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Journal Title
Mol. Pharmacol 71
Pages: 294-302
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Intrathecal administration of ATP produces long-lasting allodynia in rats : differential mechanisms in the phase of the induction and maintenance2007
Author(s)
Nakagawa, T., Wakamatsu, K., Zhang, N., Maeda, S., Minami, M., Satoh, M., Kaneko, S
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Journal Title
Neuroscience 147
Pages: 445-455
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Inhibition of glutamatergic transmission by morphine in the basolateral amygdaloid nucleus reduces pain-induced aversion2007
Author(s)
Deyama, S., Yamamoto, J., Machida, T. Tanimoto, S., Nakagawa, T., Kaneko, S., Satoh, M., Minami, M
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Journal Title
Neurosci. Res 59
Pages: 199-204
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Ca^<2+> mobilization mediated by transient receptor potential canonical 3 is associated with thrombin-induced morphological changes of 1321N1 human astrocytoma cells
Author(s)
Nakao, K., Shirakawa, H., Sugishita, A., Matsutani, I., Niidome, T., Nakagawa, T., Kaneko, S
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Journal Title
J. Neurosci. Res (in press)
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Roles of spinal GLT-1, a glial glutamate transporter, in the pathogenesis of inflammatory and neuropathic pain2008
Author(s)
Maeda, S., Kawmoto, A., Yatani, Y., Nakagawa, T., Kaneko, S.
Organizer
The 4th Seoul-Kyoto-Osaka Joint Symposium on Pharmaceutical Sciences for Young Scientists
Place of Presentation
京都
Year and Date
20080422-24
Description
「研究成果報告書概要(和文)」より
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[Presentation] Roles of spinal GLT-1, a glial glutamate transporter, in the pathogenesis of inflammatory and neuropathic pain2008
Author(s)
Maeda, S., Kawamoto, A., Yatani, Y., Nakagawa, T., Kaneko, S
Organizer
The 4th Seoul-Kyoto-Osaka Joint Symposium on Pharmaceutical Sciences for Young Scientists
Place of Presentation
Kyoto
Year and Date
20080422-24
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Spinal gene transfer of GLT-1, a glial glutamate transporter, inhibits inflammatory and neuropathic pain in rats2008
Author(s)
Maeda, S., Kawamoto, A., Yatani, Y., Nakagawa, T., Kaneko, S
Organizer
The 81st Annual Meeting of the Japanese Pharmacological Sociery
Place of Presentation
Yokohama
Year and Date
20080326-28
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Involvement of glutamatergic transmission within the ventral bed nucleus of the stria terminalis in pain-related aversion in rats2008
Author(s)
Deyama, S., Katayama, T., Nakagawa, T., Kaneko, S., Yamaguchi, T., Yoshioka, M., Minami, M
Organizer
The 81st Annual Meeting of the Japanese Pharmacological Society
Place of Presentation
Yokohama
Year and Date
20080326-28
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Ca^<2+> mobilization mediated by transient receptor potential canonical 1 is associated with thrombin-induced morphological changes of 1321N1 human astrocytoma cells2007
Author(s)
Nakao, K., Sugishita, A., Matsutani, I., Nakagawa, T., Shirakawa, H., Kaneko, S
Organizer
Neuroscience 2007 (The 37th Annual Meeting of the Society for Neuroscience)
Place of Presentation
San Diego, CA, USA
Year and Date
20071103-07
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Role of the protein kinase A activation within the bed nucleus of the stria terminalis in pain-induced aversion in rats2007
Author(s)
Deyama, S., Katayama, T., Nakagawa, T., Kaneko, S., Yamaguchi, T., Yoshioka, M., Minami, M
Organizer
Neuroscience 2007 (The 37th Annual Meeting of the Society for Neuroscience)
Place of Presentation
San Diego, CA, USA
Year and Date
20071103-07
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Role of the protein kinase A within the ventral bed nucleus of the stria terminalis in pain-induced aversion in rats2007
Author(s)
Deyama, S., Katayama, T., Nakagawa, T., Kaneko, S., Yamaguchi, T., Yoshioka, M., Minami, M
Organizer
The 28th Annual Meeting of Japanese Narcotics Research Conference
Place of Presentation
Sapporo
Year and Date
20070831-0901
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Role of the protein kinase A within the ventral bed nucleus of the stria terminalis in pain-induced aversion in rats2007
Author(s)
Deyama, S., Katayama, T., Nakagawa, T., Kaneko, S., Yamaguchi, T., Yoshioka, M., Minami, M
Organizer
The 37th Annual Meeting of Japanese Society of Neuropsychopharmacology
Place of Presentation
Sapporo
Year and Date
20070711-13
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Functional roles of TRPC receptor-activated Ca^<2+> channels in astroglia2007
Author(s)
Sugishita, A., Nakao, K., Matsutani, I., Shirakawa, H., Nakagawa, T., Kaneko, S
Organizer
The 80th Annual Meeting of the Japanese Pharmacological Society
Place of Presentation
Nagoya
Year and Date
20070314-16
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Activation of β-adrenoceptors in the bed nucleus of the stria terminalis induces conditioned place aversion and anxiety-like behaviors2007
Author(s)
Deyama, S., Katayama, T., Nakagawa, T., Kaneko, S., Yamaguchi, T., Yoshioka, M., Minami, M
Organizer
The 80th Annual Meeting of the Japanese Pharmacological Society
Place of Presentation
Nagoya
Year and Date
20070314-16
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Activation of spinal P2X-receptors produce long-lasting allodynia in rats : roles of spinal glial cells2006
Author(s)
Nakagawa, T., Wakamatsu, K., Zhang, N., Maeda, S., Satoh, M., Kaneko, S
Organizer
Neuroscience2006 (The 36th Annual Meeting of the Society for Neuroscience)
Place of Presentation
Atlanta, USA
Year and Date
20061014-18
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Noradrenergic transmission within the bed nucleus of the stria terminalis contributes to the negative affective component of pain in rats2006
Author(s)
Minami, M., Deyama, S., Akiyama, N., Hirata, M., Nakagawa, T., Kaneko, S
Organizer
Neuroscience2006 (The 36th Annual Meeting of the Society for Neuroscience)
Place of Presentation
Atlanta, USA
Year and Date
20061014-18
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Noradrenergic transmission within the BNST contributes to the negative affective component of pain2006
Author(s)
Minami, M., Deyama, S., Akiyama, N., Hirata, M., Nakagawa, T., Kaneko, S
Organizer
The 36th Annual Meeting of Japanese Society of Neuropsychopharmacology
Place of Presentation
Nagoya
Year and Date
20060914-16
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Involvement of noradrenergic transmission within the bed nucleus of the stria terminalis in the negative affective component of pain2006
Author(s)
Deyama, S., Akiyama, N., Hirata, M., Nakagawa, T., Kaneko, S., Yamaguchi, T., Yoshioka, M., Minami, M
Organizer
The 27th Annual Meeting of Japanese Narcotics Research Conference
Place of Presentation
Wakayama
Year and Date
20060901-02
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Involvement of spinal glial cells in intrathecal ATP-induced long-lasting allodynia in rats2006
Author(s)
Wakamatsu, K., Nakagawa, T., Maeda, S., Minami, M., Satoh, M., Kaneko, S
Organizer
The 27th Annual Meeting of Japanese Narcotics Research Conference
Place of Presentation
Wakayama
Year and Date
20060901-02
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Role of noradrenergic transmission within the bed nucleus of the stria terminalis in pain-related aversion in rats2006
Author(s)
Deyama, S., Akiyama, N., Hirata, M., Nakagawa, T., Kaneko, S., Minami, M
Organizer
The 31st Annual Meeting of Japan Neuroscience Society
Place of Presentation
Kyoto
Year and Date
20060719-21
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Noradrenergic transmission within the central amygdaloid nucleus contributes to the negative affective component of visceral pain in rats2006
Author(s)
Deyama, S., Takishita, A., Nakagawa, T., Tanimoto, S., Kaneko, S., Satoh, M., Minami, M
Organizer
Serotonin Club-Sixth IUPHAR Satellite Meeting on Serotonin
Place of Presentation
Hokkaido
Year and Date
20060627-30
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Role of noradrenergic transmission within the bed nucleus of the stria terminalis in somatic pain-related aversion in rats2006
Author(s)
Hirata, M., Deyama, S., Akiyama, N., Nakagawa, T., Kaneko, S., Minami, M
Organizer
Serotonin Club-Sixth IUPHAR Satellite Meeting on Serotonin
Place of Presentation
Hokkaido
Year and Date
20060627-30
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Role of noradrenergic transmission within the bed nucleus of the stria terminalis in visceral pain-related aversion in rats2006
Author(s)
Akiyama, N., Deyama, S., Hirata, M., Nakagawa, T., Kaneko, S., Minami, M
Organizer
Serotonin Club-Sixth IUPHAR Satellite Meeting on Serotonin
Place of Presentation
Hokkaido
Year and Date
20060627-30
Description
「研究成果報告書概要(欧文)」より
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