Effect of agmatine on intrathecal morphine analgesia

Objective To observe the effect of intrathecal agmatine( AG) at the spinal cord level on morphine tolerance.Methods( 1) Twenty-four SD rats were divided into four groups: control group,pure intrathecal injection( i. t.) of saline( 15 μL);morphine group,i. t. morphine( 15 μg /15 μL); AG group,i. t. AG( 12. 5 μg /15 μL); and morphine + AG group,i. t. morphine( 15 μg/5 μg) and AG( 12.5 μg/10 μL). Rats of the four groups were injected with 0.2 mg bee venom subcutaneously in the plantar5 min after i. t,and the numbers of spontaneous paw withdrawal reflex were recorded within 1 hour.( 2) Twenty-four SD rats were divided into three groups: control group,pure intrathecal saline( 15 μL); morphine tolerance group,i. t. morphine( 15 μg /5 μL)twice a day for 4 consecutive days; and morphine tolerance + AG group,i. t. morphine( 15 μg /5 μL) twice a day for 4 consecutive days,on the fourth day the rats also received AG( 12. 5 μg /10 μL). Half of the rats were examined for thermal paw withdrawal latency and mechanical withdrawal threshold after i. t,and the other half was injected with 0. 2 mg bee venom subcutaneously in the plantar 10 min after last dose; the number of spontaneous paw withdrawal reflex were recorded within 1 hour. Results( 1) Compared with the control group,the numbers of flinches of intrathecal morphine and AG groups were significantly reduced( P 0. 05).( 2) In intrathecal morphine tolerance model,the thermal paw withdrawal latency and mechanical withdrawal threshold were significantly increased in the morphine tolerance + AG group compared with the control group( P 0. 05); morphine tolerance + AG group hadsignificantly stronger inhibitory effect against spontaneous s. c. BV-induced pain,with the number of spontaneous flinches within 1 hour decreased significantly in the morphine tolerance + AG group( P 0. 05). Conclusion Intrathecal AG has synergistic effect with morphine in pain relieving,and it can also reverse the morphine tolerance induced by repeated i. t. injection.