Pain is associated with the stimulation of some behaviors and the depression of others. The present study used parallel assays of pain-stimulated and pain-depressed behaviors in rats to compare antinociception profiles for six μ-agonists that varied in efficacy (from highest to lowest: methadone, fentanyl, morphine, hydrocodone, buprenorphine, nalbuphine). Intraperitoneal injection of diluted lactic acid was a noxious stimulus to either induce stretching or depress operant responding maintained by electrical stimulation in intracranial self-stimulation (ICSS). All μ-agonists blocked both stimulation of stretching and depression of ICSS produced by 1.8% lactic acid. The high-efficacy agonists were more potent at blocking acid-induced depression of ICSS than acid-stimulated stretching, whereas lower-efficacy agonists displayed similar potency across assays. These results reveal distinctions between opioids based on efficacy at the μ-receptor, as well as support the use of parallel assays of pain-stimulated and pain-depressed behaviors to evaluate analgesic efficacy.
See article at J Pharmacol Exp Ther 2015, 352:208–217.
- Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics