Excessive spinal glutamate transmission is involved in oxaliplatin-induced mechanical allodynia: A possibility for riluzole as a prophylactic drug

Shota Yamamoto, Soichiro Ushio, Nobuaki Egashira, Takehiro Kawashiri, Shohei Mitsuyasu, Hitomi Higuchi, Nana Ozawa, Ken Masuguchi, Yuko Ono, Satohiro Masuda

研究成果: ジャーナルへの寄稿記事

8 引用 (Scopus)

抄録

Oxaliplatin, a chemotherapy medication, causes severe peripheral neuropathy. Although oxaliplatin-induced peripheral neuropathy is a dose-limiting toxicity, a therapeutic strategy against its effects has not been established. We previously reported the involvement of N-methyl-D-aspartate receptors and their intracellular signalling pathway in oxaliplatin-induced mechanical allodynia in rats. The aim of this study was to clarify the involvement of spinal glutamate transmission in oxaliplatin-induced mechanical allodynia. In vivo spinal microdialysis revealed that the baseline glutamate concentration was elevated in oxaliplatin-treated rats, and that mechanical stimulation of the hind paw markedly increased extracellular glutamate concentration in the same rats. In these rats, the expression of glutamate transporter 1 (GLT-1), which plays a major role in glutamate uptake, was decreased in the spinal cord. Moreover, we explored the potential of pharmacological therapy targeting maintenance of extracellular glutamate homeostasis. The administration of riluzole, an approved drug for amyotrophic lateral sclerosis, suppressed the increase of glutamate concentration, the decrease of GLT-1 expression and the development of mechanical allodynia. These results suggest that oxaliplatin disrupts the extracellular glutamate homeostasis in the spinal cord, which may result in neuropathic symptoms, and support the use of riluzole for prophylaxis of oxaliplatin-induced mechanical allodynia.

元の言語英語
記事番号9661
ジャーナルScientific reports
7
発行部数1
DOI
出版物ステータス出版済み - 12 1 2017

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oxaliplatin
Riluzole
Hyperalgesia
Glutamic Acid
Pharmaceutical Preparations
Amino Acid Transport System X-AG
Peripheral Nervous System Diseases
Spinal Cord
Homeostasis
Microdialysis
Amyotrophic Lateral Sclerosis
N-Methyl-D-Aspartate Receptors

All Science Journal Classification (ASJC) codes

  • General

これを引用

Excessive spinal glutamate transmission is involved in oxaliplatin-induced mechanical allodynia : A possibility for riluzole as a prophylactic drug. / Yamamoto, Shota; Ushio, Soichiro; Egashira, Nobuaki; Kawashiri, Takehiro; Mitsuyasu, Shohei; Higuchi, Hitomi; Ozawa, Nana; Masuguchi, Ken; Ono, Yuko; Masuda, Satohiro.

:: Scientific reports, 巻 7, 番号 1, 9661, 01.12.2017.

研究成果: ジャーナルへの寄稿記事

Yamamoto, Shota ; Ushio, Soichiro ; Egashira, Nobuaki ; Kawashiri, Takehiro ; Mitsuyasu, Shohei ; Higuchi, Hitomi ; Ozawa, Nana ; Masuguchi, Ken ; Ono, Yuko ; Masuda, Satohiro. / Excessive spinal glutamate transmission is involved in oxaliplatin-induced mechanical allodynia : A possibility for riluzole as a prophylactic drug. :: Scientific reports. 2017 ; 巻 7, 番号 1.
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abstract = "Oxaliplatin, a chemotherapy medication, causes severe peripheral neuropathy. Although oxaliplatin-induced peripheral neuropathy is a dose-limiting toxicity, a therapeutic strategy against its effects has not been established. We previously reported the involvement of N-methyl-D-aspartate receptors and their intracellular signalling pathway in oxaliplatin-induced mechanical allodynia in rats. The aim of this study was to clarify the involvement of spinal glutamate transmission in oxaliplatin-induced mechanical allodynia. In vivo spinal microdialysis revealed that the baseline glutamate concentration was elevated in oxaliplatin-treated rats, and that mechanical stimulation of the hind paw markedly increased extracellular glutamate concentration in the same rats. In these rats, the expression of glutamate transporter 1 (GLT-1), which plays a major role in glutamate uptake, was decreased in the spinal cord. Moreover, we explored the potential of pharmacological therapy targeting maintenance of extracellular glutamate homeostasis. The administration of riluzole, an approved drug for amyotrophic lateral sclerosis, suppressed the increase of glutamate concentration, the decrease of GLT-1 expression and the development of mechanical allodynia. These results suggest that oxaliplatin disrupts the extracellular glutamate homeostasis in the spinal cord, which may result in neuropathic symptoms, and support the use of riluzole for prophylaxis of oxaliplatin-induced mechanical allodynia.",
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