mr-2266 and Arthritis

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Animals; Arthritis; Arthritis, Experimental; Benzomorphans; beta-Endorphin; Dynorphins; Endorphins; Enkephalin, Leucine; Enkephalin, Methionine; Morphine; Naloxone; Nociceptors; Pain; Pituitary Gland, Anterior; Protein Precursors; Pyrrolidines; Rats; Receptors, Opioid; Sensory Thresholds; Spinal Cord; Thalamus

In an attempt to determine the opioid receptor class(es) which underly the two opposing effects of naloxone in models of persistent pain, we tested the action of the selective delta antagonist naltrindole, and that of the kappa antagonist MR-2266 on the bidirectional effect of systemic naloxone in arthritic rats. As a nociceptive test, we used the measure of the vocalization thresholds to paw pressure. The antagonists were administered at a dose (1 mg/kg i.v. naltrindole, 0.2 mg/kg i.v. MR-2266), without action per se but which prevents the analgesic effect of the delta agonist DTLET (3 mg/kg, i.v.) or the kappa agonist U-69,593 (1.5 mg/kg, i.v.) respectively, and does not influence the effect of morphine (1 mg/kg i.v.) or the mu agonist DAMGO (2 mg/kg, i.v.) in these animals. In arthritic rats injected with the delta antagonist, the paradoxical antinociceptive effect produced by 3 micrograms/kg i.v. naloxone was not significantly modified (maximal vocalization thresholds (% of control) were 146 +/- 9% versus 161 +/- 7% in the control group). By contrast, the hyperalgesic effect produced by 1 mg/kg i.v. naloxone was significantly reduced (maximal vocalization thresholds were 87 +/- 4% versus 69 +/- 5% in the control group). In rats injected with the kappa antagonist, the antinociceptive effect of the low dose of naloxone was almost abolished (mean vocalization thresholds were 115 +/- 3% versus 169 +/- 7%) whereas the hyperalgesic effect of naloxone 1 mg/kg i.v. was not significantly modified (mean vocalization thresholds = 70 +/- 3% and 65 +/- 3%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Analysis of Variance; Animals; Arthritis; Benzomorphans; Dose-Response Relationship, Drug; Injections, Intravenous; Male; Naloxone; Naltrexone; Narcotic Antagonists; Nociceptors; Pain; Pain Threshold; Rats; Rats, Sprague-Dawley; Receptors, Opioid, delta; Receptors, Opioid, kappa; Vocalization, Animal