Pioglitazone Attenuates Tactile Allodynia and Thermal Hyperalgesia in Mice Subjected to Peripheral Nerve Injury
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概要
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To clarify the role of peroxisome proliferator activated receptor γ (PPARγ) in neuropathic pain, we examined the effect of pioglitazone, a PPARγ agonist, on tactile allodynia and thermal hyperalgesia in a neuropathic pain model. Mice were subjected to partial sciatic nerve ligation (PSL) and given pioglitazone (1 – 25 mg/kg, p.o.) once daily. PPARγ was distributed in the neurons of the dorsal root ganglion and the dorsal horn of the spinal cord and in the adipocytes at the epineurium of the sciatic nerve in naive mice. PSL elicited tactile allodynia and thermal hyperalgesia for two weeks. Administration of pioglitazone for the first week after PSL attenuated thermal hyperalgesia and tactile allodynia, which was dose-dependent and blocked by GW9662 (2 mg/kg, i.p.), a PPARγ antagonist. Administration of pioglitazone for the second week also relieved tactile allodynia, but administration one week before PSL had no effect. A single administration of pioglitazone to mice on day 7 of PSL did not alter tactile allodynia and thermal hyperalgesia. PSL-induced upregulation of tumor necrosis factor-α and interleukin-6, which are essential for neuropathic pain, was suppressed by pioglitazone for the first week. This suggests that pioglitazone alleviates neuropathic pain through attenuation of proinflammatory cytokine upregulation by PPARγ stimulation.
- 2008-11-20
著者
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Maeda Takehiko
Department of Pharmacology, Wakayama Medical University
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Kiguchi Norikazu
Department of Pharmacology, Wakayama Medical University
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Kobayashi Yuka
Department of Pharmacology, Wakayama Medical University
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Ozaki Masanobu
Department of Toxicology, Niigata University of Pharmacy and Applied Life Science
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Kishioka Shiroh
Department of Pharmacology, Wakayama Medical University
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Ozaki M
Institute Of Space And Astronautical Science Jaxa
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Ozaki Masanobu
和歌山県立医科大学 薬理学教室
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Ozaki Masanobu
Department Of Cardiology Fukuoka University School Of Medicine
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OHNO Masanori
Dep. of Phys., Hiroshima University
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Maeda Takehiko
Department Of Pharmacology Graduate School Of Pharmaceutical Sciences Kyoto University
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Kobayashi Yuka
Department Of Cardiology And Internal Medicine Yamashiro Public Hospital
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Ozaki Masanobu
Institute Of Space And Astronautical Science Jaxa
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Ohno Masanori
Institute Of Space And Astronautical Science Japan Aerospace Exploration Agency
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Kishioka Shiroh
Department Of Pharmacology Wakayama Medical College
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Kobayashi Yuka
Department Of Biological And Environmental Chemistry Faculty Of Agriculture Tottori University
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Ozaki Masanobu
JAXA/Institute of Space and Astronautical Science
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OZAKI Masanobu
Department of High Energy Astrophysics, Institute of Space and Astronautical Science (ISAS), Japan Aerospace Exploration Agency (JAXA)
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Kiguchi Norikazu
Department of Pharmacology, Faculty of Medicine, Wakayama Medical University, Japan
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