The mechanical antihyperalgesic effect of intrathecally administered MPV-2426, a novel α2-adrenoceptor agonist, in a rat model of postoperative pain

Abstract

Background: MPV-2426 is a novel α2-adrenoceptor agonist developed for spinal pain therapy. It has proved to be effective in physiologic and neuropathic conditions. In the current study its effectiveness on mechanical hyperalgesia was assessed in a rat model of postoperative pain. Methods: Rats with intrathecal catheters were anesthetized with pentobarbital, and a 1-cm incision was made in the plantar aspect of the foot and closed. During postoperative days 1 and 2 the antihyperalgesic effects induced by intrathecal MPV-2426, clonidine, and dexmedetomidine were determined by assessing the hind limb withdrawal threshold to calibrated yon Frey hairs applied to the skin of the hind paw adjacent to the wound. Results: MPV-2426 administered into the lumbar spinal cord produced a dose-dependent (0.3-10 μg) attenuation of the mechanical hyperalgesia, and this antihyperalgesic effect was completely reversed by yohimbine (1 mg/kg, subcutaneous), an α2- adrenoceptor antagonist. Dexmedetomidine (1-3 μg) produced an equipotent antihyperalgesic effect, whereas the effect of clonidine (1-10 μg) was markedly weaker. MPV-2426 (10 μg in 20 μl) administered adjacent to the wound did not produce any effect. Preoperative treatment with an antihyperalgesic dose of MPV-2426 did not prevent the development of hyperalgesia. Conclusions: Intrathecal MPV-2426 dose-dependently attenuates postoperative hyperalgesia to mechanical stimulation because of an action on α2 adrenoceptors. Its antihyperalgesic action is as effective as that produced by dexmedetomidine and is considerably stronger than that produced by clonidine. However, preoperative treatment with MPV-2426 does not prevent the development of postoperative hyperalgesia.