Effects of ginsenoside Rg1 on apoptosis in spinal dorsal horn in development of morphine tolerance in rats with arthritis

Abstract

Objective To investigate the effects of ginsenoside Rgl on apoptosis in spinal dorsal horn in development of morphine tolerance in rats with arthritis. Methods Twenty-four healthy male SD rats weighing 280-320 g in which intrathecal（IT） catheters were successfully implanted without complication were randomized into 4 groups （n = 6 each）： group normal saline （group C）; group morphine （group M）; group ginsenoside Rgl （group G） and group morphine ＋ ginsenoside Rgl （group MG）. Arthritis was induced with complete Freund adjuivant injected into the ankle joint of fight hind limb according to the method described by Butler et al in all 24 animals. Chronic morphine tolerance was induced by IT morphine 10 μg twice a day for 7 consecutive days in groups M and MG. Ginsenoside Rgl 100 μg was given IT once a day for 7 consecutive days in groups G and MG. Paw withdrawal threshold to mechanical stimulation with von Frey filaments （MWT） was measured before induction of arthritis （T1 , baseline）, and IT drug administration （T2） and at day 1, 3, 5, 7 （T3-6） after IT administration. The rats were sacrificed after last MWT measurement and their lumbar segments of the spinal cord （L3-5） were removed for detection of apoptosis in the spinal dorsal horn by TUNEL. Results MWT was significantly decreased after induction of arthritis at T2-6 compared with the baseline value before arthritis at T1 in all 4 groups. In group M IT morphine significantly increased MWT at T3,4 compared with the baseline at T2 but the MWT was decreasing at Ts,6 indicative of development of morphine tolerance. In group MG, addition of ginsenoside Rgl to IT morphine significantly attenuate the decrease in MWT at T5, 6 -The number of apoptotic cells in spinal dorsal horn was significantly higher in groups M and MG than in group C, but was significantly lower in group MG than in group M. Conclusion Ginsenoside Rgl can prevent the development of morphine tolerance in rats with arthritis by inhibiting apoptosis in spinal dorsal horn. Key words: GINSENOSIDE ; Drug tolerance ; Morphine ; Arthritis, experimental ; Apoptosis ; Spinal cord