Tramadol and dihydroetorphine produce synergistic analgesic effect and postpones acute opiate tolerance in rats.
- Author:
Xiao-Yun MING
1
;
Wei WANG
;
Ji-Sheng HAN
;
Fei LUO
Author Information
1. Neuroscience Research Institute and Department of Neurobiology, School of Basic Medicine, Peking University, Beijing 100083, China.
- Publication Type:Journal Article
- MeSH:
Analgesics, Opioid;
administration & dosage;
pharmacology;
Animals;
Drug Synergism;
Drug Tolerance;
physiology;
Etorphine;
administration & dosage;
analogs & derivatives;
pharmacology;
Female;
Male;
Pain;
drug therapy;
physiopathology;
Rats;
Rats, Wistar;
Tramadol;
administration & dosage;
pharmacology
- From:
Acta Physiologica Sinica
2005;57(6):696-704
- CountryChina
- Language:English
-
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.
