Study On Analgesic Effect Of Ghrelin And Its Effects On Peripheral Analgesia Of Morphine

Objective: The aim of the study was to observe the effects and the possiblemechanisms of Ghrelin on acute pain at the supra spinal level, by using tailwithdrawal test and hot-plate test in mice. Meanwhile, the effects and the possiblemechanisms of Ghrelin on the analgesic effect induced by peripheral injection ofmorphine was evaluated by using tail withdrawal test in mice.Methods:1.It was evaluated that the effects and the possible mechanisms ofGhrelin on acute pain modulation at the supra spinal level in mice, by using tailwithdrawal test and hot-plate test.2. It was detected that the effects and the possible mechanisms of Ghrelin on theanalgesic effect induced by peripheral injection of morphine in mice, by using tailwithdrawal test.Results:1. Ghrelin(0.03-1nmol)injected intracerebroventriculary(mouse, i.c.v.)caused a dose-dependant increasing of tail withdrawal latency and paw-licking/jumping latency in the tail withdrawal test and the hot-plate test, respectively.2. The analgesic effect was blocked by opioid receptor antagonist naloxone(i.c.v.,10nmol co-injection or i.p.,10mg/kg,10min prior to Ghrelin), which inducedby intracerebroventricular injection of small dose of Ghrelin in both tail withdrawaltest and hot-plate test.3. The analgesic effect was blocked by co-injection with10nmol GHS-R1αantagonist [D-Lys3]-GHRP-6, which induced by Ghrelin(1nmol, i.c.v.), while [D-Lys3]-GHRP-6(10nmol)alone induced neither hyperalgesia nor analgesia.4. The analgesic effect was decreased by intracerebroventricular injection oflarge dose of Ghrelin in a dose-dependant manner, which induced by peripheralinjection of morphine.5. The peripheral analgesia of morphine was decreased by intracerebroventr-icular injection of large dose of Ghrelin. This effect could not be blocked by intrac-erebroventricular injection of GHS-R1α. So the mechanism of Ghrelin’s decreasing the peripheral analgesia of morphine was not through GHS-R1α.Conclusion: we demonstrated that small dose of Ghrelin exerted its analgesiceffect through GHS-R1α and opioid receptor. At the same time, central administrationof large dose of Ghrelin could block the effect of analgesia induced by morphineadministered at the peripheral level.