Introduction . Various studies su ggest Menaquinone-4 in inhibiting the pain and in flammation. Vitamin K2 in hibits the release of b radykinin and NMDA receptors activity in the spinal co rd can b e con sidered for its probable analgesic effect. Systemic administration of opioid s such as morphine causes pain relief by inhibitory effects on neu rotransmitter sy stem s, nitric oxide (NO) and NMDA receptors. Interference between intrathecal adm inistration (i.t) of Menaquinone-4 an d systemic morphine ind uced an algesia/hyp eralgesia in formalin test were investigated in this study. Materials and method s. The adu lt male Wistar rats (250-300 g) were used. Rats were then sub jected to i.t. surgery. Gro ups inclu de: control, sham (salin +DMSO، i.t) and treatmen ts consists o f vitamin K2 (2µg/10 µl, i.t), initially hy peralgesia and analgesia doses of morphine were intraperitoneal injected, after 25 minute intrathecal adm in istration of v itamin K2 was p erfo rmed, a subplantar 0.05 ml injection of fo rmalin %2.5 in th e right hind paw was tak e p laced 5 minute later, then animal responses to pain was recorded for 60 m in utes. Resu lts. Intrathecal administration of vitamin K2 (2µ g/10µl) significantly increased morphine induced analgesia (P<0.001) and reduced morphine induced hyperalgesia, So that even in the latest case hyp eralgesia was converted to a redu ction in pain respon ses (P<0.001 ). Conclusion. Vitamin K2 potentiated the analg esic effect o f morphine may be b ecause of its indirect inhibitory effect on the activ ity of NMDA receptors and an other d irect effects wh ich still is not so clear; also inhibitory fu nction of v itamin K2 on th e activity of iNOS and thus NO produ ction has to be co ncidered. So perhaps vitamin K2 and morphine produ ce a syn ergistic analgesic effect via some com mon pathways.

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