Increased analgesic potency of morphine following repeated anaphylactoid reaction by compound 48/80 involves cyclooxygenase products of arachidonic acid

The role of rat brain mast cell histamine in the analgesic effect of morphine, and the possible involvement of cyclooxygenase products of arachidonic acid, was studied in the tail-flick and hot-plate tests. In animals submitted to repeated anphylactoid reactions (by injecting compound 48/80 intracerebroventricularly, 20 μg/5 μl, for five days) morphine (10 mg/kg, sc, 24 hrs after the last treatment with compound 48/80) showed a significant enhancement in its antinociceptive properties and a marked increase in the duration of action in both analgesic tests, compared to saline-pretreated rats. In rats pretreated with combined compound 48/80 (20 μg, icv) plus the nonsteroidal antiinflammatory drug acetylsalicyclic acid (30 mg/kg, ip. 60 min before compound 48/80) for five days, the effect of morphine (10 mg/kg, sc, 24 hrs after) was reduced both in its intensity and in its duration of analgesic efficacy, compared to saline-pretreated rats. Since in this study acetylsalicylic acid-pretreatment was shown to inhibit the morphine response in tailflick and hot-plate tests only in animals lacking in brain mast cell histamine following icv administration of compound 48/80, results suggest that cyclooxygenase products of arachidonic acid may be intermediates in the adaptive processes involved in shock/stress functional disturbances in rat brain. © 1993 Birkhäuser Verlag.