Milnacipran inhibits oxaliplatin-induced mechanical allodynia through spinal action in mice.
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.
Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences.
Tsugunobu
T
Andoh
Ryo
R
Kitamura
Yasushi
Y
Kuraishi
D000818:Animals; D000970:Antineoplastic Agents; D003521:Cyclopropanes / Q000008:administration & dosage / Q000627:therapeutic use*; D004333:Drug Administration Routes; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D008810:Mice, Inbred C57BL; D000078764:Milnacipran; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D013116:Spinal Cord / Q000187:drug effects
D000970:Antineoplastic Agents; D003521:Cyclopropanes; D000078764:Milnacipran; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D017367:Selective Serotonin Reuptake Inhibitors