Synergistic antinociceptive interaction between aspirin and tramadol, the atypical opioid analgesic, in the rat

In order to assess a possible synergistic antinociceptive interactions, the analgesic effects of aspirin per ss (acetyl salicylic acid or “ASA”), a nonsteroidal anti-inflammatory drug (NSAID), and tramadol s.c. (TRA), an atypical opioid analgesic, administered either separately or in combination were determined in a model of pain-induced functional impairment in the rat, groups of six rats received either vehicle, ASA (175.4, 312.1, 555.1, 987.0, 1, 755.3, or 3, 121.2 μmol/kg) and TRA (21.3, 38.0, 67.5, 120.0, or 213.5 μmol/kg), or a combination of ASA and TRA (24 different combinations). This allowed us to detect the interaction profile of these combinations. The ED50 for either ASA or TRA were 1, 173.5 ± 7.4 μmol/kg and 141.5 ± 6.8 μmol/kg, respectively. The data obtained confirmed an interaction between ASA and TRA and showed antinociception that may be additive or synergistic, depending on the drug ratio administered. Furthermore, eight combinations showed various degrees of potentiation (P < .01), whereas the others (16) exhibited analgesic effects not different from that of ASA alone. The combination of ASA (3, 121.2 μmol/kg) and TRA (120.0 μmol/kg) produced the maximum analgesic effect. However, the combination of ASA (987/ μmol/kg) with TRA (120.0 μmo/kg) produced the highest potentiation effects. This study clearly showed (1) that there is an interaction between ASA and TRA and (2) which combination of these analgesic drugs produced either the maximum analgesic effect or the highest degree of potentiation in the rat. © 1995 Wiley-Liss, Inc.