Milnacipran inhibits itch-related responses in mice through the enhancement of noradrenergic transmission in the spinal cord

We investigated whether milnacipran, a serotonin-noradrenaline reuptake inhibitor, exhibits an antipruritic effect through the spinal action in mice. Intrathecal injections of milnacipran (0.1 - 10 μg/site) significantly suppressed serotonin-induced biting, which is an itch-related response. However, such an effect was not observed with fluvoxamine (10 μg/site), which is a selective serotonin reuptake inhibitor. Furthermore, an intraperitoneal injection of milnacipran (10 mg/kg) inhibited serotonin-induced biting. When phentolamine (1.0 μg/site), a non-selective α-adrenoceptor antagonist, was intrathecally injected, it inhibited the above response of milnacipran. These results suggest that milnacipran suppresses itching through the inhibition of noradrenaline reuptake in the spinal cord.