Morphine, U50-488, and (-)-lobeline produced dose-related shortening of a low-intensity thermally evoked tail avoidance response (LITETAR) (e.g., hyperalgesia) when microinjected into the dorsal posterior mesencephalic tegmentum (DPMT) of conscious rats. The hyperalgesic potency of (-)-lobeline was greater than either morphine or U50-488. With higher doses, morphine's hyperalgesic actions diminished and prolongation of the LITETAR (e.g., analgesia) was observed. Naltrexone produced analgesia in the DPMT that diminished with increasing dose. The hyperalgesic actions of morphine, U50-488, and (-)-lobeline further suggest the presence of kappaergic opioid and nicotinic mechanisms in the DPMT of rats. The hyperalgesic actions of U50-488, a highly specific opioid kappa-receptor agonist, strongly suggest the presence of a kappa-opioidergic hyperalgesic mechanism in the DPMT.
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer Analgesics