The Monoamine-Mediated Antiallodynic Effects of Intrathecally Administered Milnacipran, a Serotonin Noradrenaline Reuptake Inhibitor, in a Rat Model of Neuropathic Pain

In Brief 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 μg and 100 μg. The effect lasted for 7 h after injection of 100 μg (P < 0.05). The antiallodynic effect of 30 μg of milnacipran was attenuated by intrathecal coadministration of 30 μg of yohimbine, an α2-adrenoceptor antagonist, 30 μg of methysergide, a serotonin receptor antagonist, or 30 μg 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 μg) or maprotiline (10 to 100 μg). 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. IMPLICATIONS: Intrathecal administration of a new type of antidepressant, milnacipran, a serotonin noradrenaline reuptake inhibitor, mediates antiallodynic effects in rats with neuropathic pain, and spinal monoamine receptors are involved in this action. Intrathecal administration of milnacipran might be effective for suppression of neuropathic pain.