論文

査読有り
2014年11月

The Contribution of Gi/o Protein to Opioid Antinociception in an Oxaliplatin-Induced Neuropathy Rat Model

JOURNAL OF PHARMACOLOGICAL SCIENCES
  • Tomoe Kanbara
  • ,
  • Atsushi Nakamura
  • ,
  • Keiko Takasu
  • ,
  • Koichi Ogawa
  • ,
  • Masahiro Shibasaki
  • ,
  • Tomohisa Mori
  • ,
  • Tsutomu Suzuki
  • ,
  • Minoru Hasegawa
  • ,
  • Gaku Sakaguchi
  • ,
  • Toshiyuki Kanemasa

126
3
開始ページ
264
終了ページ
273
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1254/jphs.14133FP
出版者・発行元
JAPANESE PHARMACOLOGICAL SOC

Oxaliplatin is a chemotherapeutic agent that induces chronic refractory neuropathy. To determine whether opioids effectively relieve this chronic neuropathy, we investigated the efficacies of morphine, oxycodone, and fentanyl, and the mechanisms underlying opioid antinociception, in oxaliplatin-induced neuropathy in rats. Rats exhibited significant mechanical allodynia following 2 weeks of chronic oxaliplatin administration. Within the range of doses that did not induce sedation and/or muscle rigidity, morphine (3 mg/kg, subcutaneously, s.c.) and oxycodone (0.3 - 0.56 mg/kg, s.c.) completely reversed oxaliplatin-induced mechanical allodynia, whereas fentanyl (0.017 - 0.03 mg/kg, s.c.) showed partial antinociception. The antinociception of the optimal doses of morphine and oxycodone were completely inhibited by pertussis toxin (PTX; 0.5 mu g/rat, i.c.v.), a Gi/o protein inhibitor, while the partial effect of fentanyl was not affected in the oxaliplatin model. In the [S-35]-GTP gamma S binding assay, activation of mu-opioid receptor by fentanyl, but not by morphine or oxycodone, in the mediodorsal thalamus was significantly reduced in oxaliplatin-treated rats. These results indicate that the lower antinociceptive potency of fentanyl in the oxaliplatin model might in part result from the loss of PTX-sensitive Gi/o protein activation, and the degree of Gi/o protein activation might be related to the potency of antinociception by opioids in this model.

リンク情報
DOI
https://doi.org/10.1254/jphs.14133FP
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/25346041
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000345551900009&DestApp=WOS_CPL
ID情報
  • DOI : 10.1254/jphs.14133FP
  • ISSN : 1347-8613
  • eISSN : 1347-8648
  • PubMed ID : 25346041
  • Web of Science ID : WOS:000345551900009

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