Tramadol and dihydroetorphine produce synergistic analgesic effect and postpones acute opiate tolerance in rats

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MING Xiao-Yun()
WANG Wei()
HAN Ji-Sheng()
LUO Fei()
Journal Title:
Volume 57, Issue 06, 2005
Key Word:
tramadol;dihydroetorphine;synergistic effect;analgesia;acute tolerance

Abstract: The present study investigated whether a co-application of tramadol (TRA) and dihydroetorphine (DHE) would exert a synergy in analgesic effect and delay acute tolerance development. Intraperitoneal injection of TRA (in mg) and subcutaneous injection of DHE (in ng) were delivered in fixed proportions (1:6.25, 1:12.5, 1:25, 1:50, 1:100, and 1:200). The effect of analgesia was accessed by tail-flick test and analyzed with isobolographic analysis. For test of acute tolerance, six successive injections of either TRA (20 mg/kg) alone, DHE (1 000 ng/kg) alone, or a combination of TRA (20 mg/kg) and DHE (250 ng/kg) were administered. We found that (1)except for 1 mg: 6.25 ng and 1 mg: 50 ng, combinations, all the other ratios produced a significant synergy in their analgesic effect; (2)the effect of analgesia induced by repeated TRA plus DHE injections lasted significantly longer, indicating a slower onset of acute tolerance. These results indicate that TRA and DHE injections in certain dose ratios can induce synergistic analgesia, which is resistant against the development of acute tolerance.

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