Opioids can induce analgesia and also hyperalgesia in humans and in animals. It has been shown that acute administration of morphine induced a hyperalgesic response at an extremely low dose. In addition, chronic injection of morphine can also induce hyperalgesic states. Although the behavioral outputs are similar but the exact mechanism(s) underlying such morphine-induced hyperalgesia has not yet been clarified. Here, we have investigated cellular events involved in low-dose and chronic morphine hyperalgesia in male Wistar rats. The data showed that acute (0.01μg i.t.) and chronic (20μg i.t., twice daily for 7 days) morphine could elicit hyperalgesia as assessed by the tail-flick test. Gas Mrna and protein levels increased significantly in both hyperalgesic situations in the dorsal half of the lumbar spinal cord. Furthermore, the levels of Gb mRNA and protein were increased by chronic administration of morphine. The tissue AMP levels were not affected by morphine treatment at hyperalgesic doses. Nifedipine, an L-type calcium channel blocker, antagonized the hyperalgesia induced by the low-dose of and also by the chronic morphine. Furthermore, pretreatment with the selective protein kinase C (PKC) inhibitor, chelerytrine, resulted in prevention of the both types of morphine-induced hyperalgesia. KT 5720, specific inhibitor of protein kinase A (PKA), did not evidence any effect on low-dose morphine-induced hyperalgesia while prevented chronic morphineinduced hyperalgesia. These results indicate a role for Gas, the PLC-PKC pathway and L-type calcium channels in both intrathecal low-dose and chronic morphine-induced hyperalgesia in rats. Activation of PKA signaling appears to play a major role just in the induction of hyperalgesia by chronic morphine.