The monoamine-mediated antiallodynic effects of intrathecally administered milnacipran, a serotonin noradrenaline reuptake inhibitor, in a rat model of neuropathic pain.
Antidepressants are often used to treat neuropathic pain. In the present study, we determined the antiallodynic effects of selective monoamine reuptake inhibitors in the spinal cord in a rat model of neuropathic pain. Mechanical allodynia was produced by tight ligation of the left L5 and L6 spinal nerves and determined by applying von Frey filaments to the left hindpaw. A serotonin noradrenaline reuptake inhibitor, milnacipran, a selective serotonin reuptake inhibitor, paroxetine, or a selective noradrenaline reuptake inhibitor, maprotiline, was administered intrathecally via a chronically implanted catheter. Milnacipran produced dose-dependent antiallodynic effects at doses between 3 microg and 100 microg. The effect lasted for 7 h after injection of 100 microg (P < 0.05). The antiallodynic effect of 30 microg of milnacipran was attenuated by intrathecal coadministration of 30 microg of yohimbine, an alpha(2)-adrenoceptor antagonist, 30 microg of methysergide, a serotonin receptor antagonist, or 30 microg of atropine, a muscarinic receptor antagonist (P < 0.01, respectively). Intraperitoneal administration of milnacipran had no antiallodynic effects at doses of 3 to 30 mg/kg. Antiallodynic effects were not produced by intrathecal administration of paroxetine (10 to 100 microg) or maprotiline (10 to 100 microg). These findings suggest that simultaneous inhibition of serotonin and noradrenaline reuptake in the spinal cord is essential to mediate antiallodynic effects. Milnacipran might be effective for suppression of neuropathic pain.
Obata
Hideaki
H
Department of Anesthesiology, Gunma University Graduate School of Medicine, Gunma, Japan.
Saito
Shigeru
S
Koizuka
Shiro
S
Nishikawa
Koichi
K
Goto
Fumio
F
D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use*; D000818:Animals; D003521:Cyclopropanes / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D007278:Injections, Spinal; D008297:Male; D000078764:Milnacipran; D010146:Pain / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D013116:Spinal Cord / Q000187:drug effects*
D018759:Adrenergic Uptake Inhibitors; D003521:Cyclopropanes; D000078764:Milnacipran; D017367:Selective Serotonin Reuptake Inhibitors