Milnacipran Inhibits Oxaliplatin-Induced Mechanical Allodynia through Spinal Action in Mice

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  • Andoh Tsugunobu
    Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences
  • Kitamura Ryo
    Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences
  • Kuraishi Yasushi
    Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences

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Abstract

We investigated whether milnacipran, a serotonin–noradrenaline reuptake inhibitor, would have therapeutic effect on oxaliplatin-induced mechanical allodynia in mice. A single intraperitoneal injection of oxaliplatin (3 mg/kg) induced mechanical allodynia, which peaked on day 10 after injection and almost completely subsided by day 20. Ten days post-oxaliplatin injection, the intraperitoneal administration of milnacipran (3–30 mg/kg) significantly and dose-dependently inhibited the established mechanical allodynia. Intrathecal injections of milnacipran (2.1–21 µg/site) also significantly and dose-dependently inhibited mechanical allodynia, but intracisternal and intracereboventricular injections at the same doses did not. The present results suggest that milnacipran is effective against oxaliplatin-induced mechanical allodynia and that the antiallodynic effect is mainly mediated by actions on the spinal cord.

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