Antihistamines and steroids, targeting peripheral tissues, have been used as first-line drugs in the treatment of chronic pruritus. Here, we focused on mirogabalin (MGB) and pregabalin (PGB), gabapentinoids that are widely used to treat neuropathic pain, to explore their potential antipruritic effects in several acute and chronic itch models. MGB and PGB, when injected i.p., i.c.v., or i.t., inhibited scratching behavior induced by chloroquine (CQ; histamine-independent pruritogen) in the neck model of acute itch. MGB (i.p., i.c.v., or i.t.) also reduced biting and licking behaviors reflecting acute itch and pain sensation, respectively, after CQ injection into the front of the left calf, while PGB produced apparent antipruritic effects only when it was injected i.t. in this calf model. The antipruritic effects of MGB and PGB were also examined under chronic itch conditions induced by applying 1-fluoro-2,4-dinitrobenzene (DNFB) repeatedly to the nape of the neck. I.p. injection of MGB and PGB, when used therapeutically or prophylactically, suppressed spontaneous scratching behavior and the development of chronic itch, respectively. Therefore, gabapentinoids are considered to be effective as the therapeutic agents acting on the central nervous system including the spinal cord for antihistamine-refractory chronic itch.