The heparin binding growth factors midkine and pleiotrophin regulate the antinociceptive effects of morphine through α2-adrenergic independent mechanisms

► We studied pain processing and morphine antinociceptive effects in MK knockout mice. ► Nociceptive transmission is not altered by the absence of endogenous midkine. ► Morphine antinociceptive effects at the spinal level are enhanced in MK-/- mice. ► Enhanced morphine effects in MK and PTN KO mice are not related to adrenergic changes. ► Differences between morphine-treated MK-/- and PTN-/- mice are discussed.