The mechanical antihyperalgesic effect of intrathecally administered MPV-2426, a novel alpha(2)-adrenoceptor agonist, in a rat model of postoperativepain

Background MPV-2426 is a novel alpha(2)-adrenoceptor agonist developed for spinal pain therapy. It has proved to be effective In physiologic and neuro pathic conditions. In the current study its effectiveness on mechanical hyp eralgesia was assessed in a rat model of postoperative pain. Methods: Rats with intrathecal catheters were anesthetized with pentobarbit al, and a 1-cm incision was made in the plantar aspect of the foot and clos ed. 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 von Frey hairs a pplied 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 mu g) attenuation of the mechanical hyperalgesia, and thi s antihyperalgesic effect was completely reversed by yohimbine (1 mg/kg, su bcutaneous), an alpha(2)-adrenoceptor antagonist. Dexmedetomidine (1-3 mu g ) produced an equipotent antihyperalgesic effect, whereas the effect of clo nidine (1-10 mu g) was markedly weaker. MPV-2426 (10 mu g in 20 mu l) admin istered adjacent to the wound did not produce any effect. Preoperative trea tment with an antihyperalgesic dose of MPV-2426 did not prevent the develop ment of hyperalgesia, Conclusions: Intrathecal MPV-2426 dose-dependently attenuates postoperative hyperalgesia to mechanical stimulation because of an action on alpha(2) ad renoceptors. Its antihyperalgesic action Is as effective as that produced b y dexmedetomidine and is considerably stronger than that produced by clonid ine. However, preoperative treatment with MPV-2426 does not prevent the dev elopment of postoperative hyperalgesia.