Establishment of Opioid-Induced Rewarding Effects Under Oxaliplatin- and Paclitaxel-Induced Neuropathy in Rats

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  • Mori Tomohisa
    Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Japan
  • Kanbara Tomoe
    Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Japan Pain & Neurology, Discovery Research Laboratories, Shionogi & Co., Ltd., Japan
  • Harumiya Masato
    Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Japan
  • Iwase Yoshiyuki
    Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Japan
  • Masumoto Aki
    Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Japan
  • Komiya Sachiko
    Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Japan
  • Nakamura Atsushi
    Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Japan Pain & Neurology, Discovery Research Laboratories, Shionogi & Co., Ltd., Japan
  • Shibasaki Masahiro
    Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Japan
  • Kanemasa Toshiyuki
    Pain & Neurology, Discovery Research Laboratories, Shionogi & Co., Ltd., Japan
  • Sakaguchi Gaku
    Pain & Neurology, Discovery Research Laboratories, Shionogi & Co., Ltd., Japan
  • Suzuki Tsutomu
    Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Japan

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Abstract

The rewarding effects of μ-receptor agonists can be suppressed under several pain conditions. We recently showed that clinically used μ-receptor agonists possess efficacies for relieving the neuropathic pain induced by chemotherapeutic drug in rats; however, it is possible that the use of μ-receptor agonists may trigger the rewarding effects even under chemotherapeutic drug–induced neuropathic pain. Nevertheless, no information is available regarding whether μ-receptor agonists produce psychological dependence under chemotherapeutic drug–induced neuropathic pain. Therefore, we examined the effects of neuropathy induced by chemotherapeutic drugs on the rewarding effects of morphine, oxycodone, and fentanyl in rats. Repeated treatment with oxaliplatin or paclitaxel produced neuropathy as measured by the von Frey test. Rewarding effects produced by antinociceptive doses of μ-receptor agonists were not suppressed under oxaliplatin- or paclitaxel-induced neuropathy. Furthermore, the morphine-induced increase in the release of dopamine from the nucleus accumbens, which is a critical step in the rewarding effects of μ-receptor agonists, was not altered in paclitaxel-treated rats. These results suggest that the rewarding effects of μ-receptor agonists can still be established under oxaliplatin- or paclitaxel-induced neuropathic pain. Therefore, patients should be carefully monitored for psychological dependence on μ-receptor agonists when they are used to control chemotherapeutic drug-induced neuropathic pain.

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