Preventive and Alleviative Effect of Tramadol on Neuropathic Pain in Rats: Roles of <i>α</i><sub>2</sub>-Adrenoceptors and Spinal Astrocytes

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  • Sakakiyama Minoru
    Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan
  • Maeda Sanae
    Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan
  • Isami Kouichi
    Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan
  • Asakura Kayoko
    Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan
  • So Kanako
    Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan
  • Shirakawa Hisashi
    Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan
  • Nakagawa Takayuki
    Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Japan
  • Kaneko Shuji
    Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan

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  • Preventive and Alleviative Effect of Tramadol on Neuropathic Pain in Rats : Roles of α₂-Adrenoceptors and Spinal Astrocytes

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Abstract

The acute analgesic effect of tramadol has been extensively investigated; however, its long-term effect on neuropathic pain has not been well clarified. In this study, we examined the effects of repeated administration of tramadol on partial sciatic nerve ligation–induced neuropathic pain in rats. Each drug was administered once daily from 0 – 6 days (preventive effect) or 7 – 14 days (alleviative effect) after the surgery. Mechanical allodynia was evaluated just before (preventive or alleviative effect) and 1 h after (analgesic effect) drug administration. Like morphine, first administration of tramadol (20 mg/kg) showed an acute analgesic effect on the developed mechanical allodynia, which was diminished by naloxone. Like amitriptyline, repeated administration of tramadol showed preventive and alleviative effects on the mechanical allodynia that was diminished by yohimbine, but not naloxone. The alleviative effects of tramadol lasted even after drug cessation or in the presence of yohimbine. Repeated administration of tramadol increased the dopamine β-hydroxylase immunoreactivity in the spinal cord. Furthermore, tramadol inhibited the nerve ligation–induced activation of spinal astrocytes, which was reduced by yohimbine. These results suggest that tramadol has both μ-opioid receptor–mediated acute analgesic and α2-adrenoceptor–mediated preventive and alleviative effects on neuropathic pain, and the latter is due to α2-adrenoceptor–mediated inhibition of astrocytic activation.

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