ANALGESIC INTERACTIONS PRODUCED BY DIPYRONE AND EITHER MORPHINE OR D-PROPOXYPHENE IN THE PAIN-INDUCED FUNCTIONAL IMPAIRMENT MODEL IN RAT

The analgesic synergism of drug mixtures containing dipyrone in combin ation with either morphine or d-propoxyphene were examined in the pain -induced functional impairment model in the rat (PIFIR). Pain was prod uced by intra-articular injection of uric acid in the right hind limb, inducing its dysfunction. Animals then received the following treatme nts: dipyrone (160, 285, 506, 900, 1,600 or 2,846 mu moles.kg(-1), sc) , morphine (3, 6, 10, 18, 31, or 55 mu moles.kg(-1), sc), d-propoxyphe ne (84, 150, 266, 473, or 841 mu moles.kg(-1), sc), or a combination u sing the ED(33) of each drug, namely, dipyrone/morphine (834/18 mu mol es.kg(-1)) or dipyrone/d-propoxyphene (834/187 mu moles.kg(-1)). The r ecovery of functionality after the above treatments was considered as an expression of analgesia. The analgesic effects produced by the comb ination dipyrone/morphine were similar to those expected on the basis of addition of analgesic effects of the individual drugs. However, ana lgesia produced by the combination dipyrone/d-propoxyphene was signifi cantly higher (P<0.01) than that induced by each component alone. The percent change was 33% over the addition of individual analgesic effec ts. The analysis of the time-course curve of the simultaneous administ ration of dipyrone/d-propoxyphene showed a maximum of analgesia of 95% at 1 h after administration and then persisted until the end of the e xperiment (up to 3 h). The total analgesic effect determined from the area under the time-course curve showed 332.5 area units; this represe nted the highest analgesic effect among the drugs tested. These result s are relevant in view of the inability of dipyrone, morphine, and d-p ropoxyphene to produce that highest analgesic effect. (C) 1994 Wiley-L iss, Inc.