We have recently reported that systemic administration of the KCNQ (Kv7) K⁺ channel opener retigabine produces analgesic and antipruritic effects. In this study, we further explored the analgesic and antipruritic effects of retigabine behaviorally and analyzed its analgesic mechanisms electrophysiologically. In the cheek model, intraperitoneal injection of retigabine inhibited wiping behavior elicited by capsaicin injection reflecting pain sensation and scratching behavior elicited by chloroquine or compound 48/80 reflecting itch sensation. In the calf model, intrathecal injection of retigabine attenuated licking behavior after capsaicin injection reflecting pain sensation and biting behavior after chloroquine or compound 48/80 injection reflecting itch sensation, indicating that the spinal cord is an important site of action of retigabine. In dorsal horn neurons of spinal cord slices prepared from mice developing mechanical allodynia after partial sciatic nerve ligation, retigabine suppressed A-fiber-evoked monosynaptic EPSCs but not C-fiber-evoked EPSCs, while mEPSCs were not affected, suggesting that reduction of monosynaptic excitatory transmission from A-fibers contributes to the analgesic effect of retigabine, and that its antipruritic effect most likely involve spinal intrinsic neurons.