Milnacipran inhibits oxaliplatin-induced mechanical allodynia through spinal action in mice

Biol Pharm Bull. 2015;38(1):151-4. doi: 10.1248/bpb.b14-00581.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents*
  • Cyclopropanes / administration & dosage
  • Cyclopropanes / therapeutic use*
  • Drug Administration Routes
  • Hyperalgesia / chemically induced
  • Hyperalgesia / drug therapy*
  • Male
  • Mice, Inbred C57BL
  • Milnacipran
  • Organoplatinum Compounds*
  • Oxaliplatin
  • Selective Serotonin Reuptake Inhibitors / administration & dosage
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Spinal Cord / drug effects

Substances

  • Antineoplastic Agents
  • Cyclopropanes
  • Organoplatinum Compounds
  • Serotonin Uptake Inhibitors
  • Oxaliplatin
  • Milnacipran