Chlorpromazine hyperalgesia antagonizes clonidine analgesia, but enhances morphine analgesia in rats tested in a hot-water tail-flick paradigm

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Abstract
Seventy-six male Sprague-Dawley rats were tested in a hot-water (55°±0.5° C) tail-flick paradigm. Tail-flick latencies (TFL) were obtained at 30 and 15 min before intraperitoneal injection of either morphine (2.5, 5.0 and 10.0 mg/kg) clonidine (25, 50, 100 and 200 μg/kg), chlorpromazine (CPZ, 2.5 and 5.0 mg/kg), dual injections of these drug combinations, or a saline control injection. Further TFL measures were taken immediately following drug administration and thereafter at 15 min intervals. The mean of the pre-drug TFL's served as each rat's baseline. All other TFL's were calculated as percentage changes from that baseline. Mean changes were determined for each treatment group and differences between groups, at each test time, were analysed. Our results demonstrated morphine and clonidine analgesia but CPZ hyperalgesia. The drug interaction studies revealed that morphine analgesia is enhanced by coadministration of either clinidine or CPZ but that clonidine analgesia is antagonized by chlorpromazine. These data suggest that morphine and clonidine exert their analgesic effects through different neurochemical mechanisms. It is particularly interesting that the clonidine-CPZ combination should result in TFL's similar to baseline levels, even though both drugs are sedatives. The investigation emphasizes the value of chlorpromazine as a pharmacological tool in analgesic research because of its ability to induce hyperalgesia even though it is a sedating agent.