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 sigma s (acetyl salicylic acid or ''ASA''), a nonsteroidal anti-inflammatory drug (NSAID), and tramad ol s.c. (TRA), an atypical opioid analgesic, administered either separ ately or in combination were determined in a model of pain-induced fun ctional impairment in the rat, groups of six rats received either vehi cle, ASA (175.4, 312.1, 555.1, 987.0, 1,755.3, or 3,121.2 mu mol/kg), TRA (21.3, 38.0, 67.5, 120.0, or 243.5 mu mol/kg), or a combination of ASA and TRA (24 different combinations). This allowed us to detect th e interaction profile of these combinations. The ED(50) for either ASA or TRA were 1,173.5 +/- 7.4 mu mol/kg and 141.5 +/- 6.8 mu mol/kg, re spectively. The data obtained confirmed an interaction between ASA and TRA and showed antinociception that may be additive or synergistic, d epending on the drug ratio administered. Furthermore, eight combinatio ns showed various degrees of potentiation (P < .01), whereas the other s (16) exhibited analgesic effects not different from that of ASA alon e. The combination of ASA (3,121.2 mu mol/kg) and TRA (120.0 mu mol/kg ) produced the maximum analgesic effect. However, the combination of A SA (987/mu mol/kg) with TRA (120.0 mu mo/kg) produced the highest pote ntiation effects. This study clearly showed 1) that there is an intera ction between ASA and TRA and 2) which combination of these analgesic drugs produced either the maximum analgesic effect or the highest degr ee of potentiation in the rat. (C) 1995 Wiley-Liss, Inc.