RESUMO
OBJECTlVE To investigate the effect of Guiyuan tablets on the analgesic effect of morphine and morphine-induced tolerance and hyperalgesia. METHODS ① The model of morphine-induced acute tolerance Mice were ig treated with Guiyuan tablets 200, 400 and 800 mg·kg-1 and 15 min later were sc treated with morphine 10 mg·kg-1 every hour for consecutive 9 h. At 24 and 48 h, they were sc treated with morphine 10 mg·kg-1 alone, respectively.②The model of morphine-induced chronic tolerance Mice were ig treated with Guiyuan tablets 200, 400 and 800 mg·kg-1 and 15 min later were sc treated with morphine 10 mg·kg-1 every day for consecutive 8 d. On d 9, the mice were sc treated with morphine 10 mg·kg-1 alone. ③ The model of morphine-induced established tolerance. Mice were sc treated with morphine 10 mg·kg-1 every day for consecutive 8 d. On d 1, d 4 or d 7, the mice began to be ig co-administered with Guiyuan 200 mg·kg-1 . On d 9, they were sc treated with morphine 10 mg·kg-1 alone. The hot-plate test was used to detect the values of the baseline latency ( T0 ) and the post-treatment latency ( T1 ) before the percentage of maximal possible analgesic effect (%MPAE) was calculated. Spec-trophotometry was used to detect the nitric oxide synthase ( NOS) activity and the nitric oxide ( NO) con-tent in the tissue of the spinal cord. RESULTS The ED50 of the analgesic effect of Guiyuan tablets was 523.5 mg·kg-1 in the hot-plate test. Guiyuan tablets 200 and 400 mg·kg-1 prolonged the duration of mor-phine anti-nociception and deceased its ED50 from 4.67 to 3.14 and 0.65 mg·kg-1, respectively. ln the models of both acute and chronic tolerance, Guiyuan tablets prevented the decrease of the%MPAE and the baseline latencies ( P<0. 05 ) . ln the model of morphine-induced established tolerance, Guiyuan tablets rapidly reversed the decrease of%MPAE( P<0.05) , and this compound preparation which began to be co-administered with morphine from d 1 could significantly inhibit the increase of the NOS activity and NO content induced by morphine in the spinal cord ( P<0.01) . CONCLUSlON Guiyuan tablets are capable of enhancing the analgesic effect of morphine, prolonging the duration of morphine anti-nocicep-tion, preventing the development of morphine-induced tolerance and hyperalgesia, and might have neuroprotective effect.