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PAIN MEDICINE

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

Department of Anesthesiology, Gunma University Graduate School of Medicine, Gunma, Japan

Address correspondence and reprint requests to Hideaki Obata, MD, Department of Anesthesiology, Gunma University Graduate School of Medicine, 3–39–22 Showa, Maebashi, Gunma 371–8511, Japan. Address e-mail to hobata{at}showa.gunma-u.ac.jp.

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 ₂-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.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999