title: Contralateral but not systemic administration of the kappa-opioid agonist U-50,488H induces anti-nociception in acute hindpaw inflammation in rats.
abstract: 1. The anti-nociceptive effects of contralateral administration of kappa-opioid agonist U-50,488H were investigated in rats. 2. Inflammation was induced by unilateral injection of 1% carrageenan into the right hindpaw. Prior to carrageenan injection, U-50,488H or saline was administered into the left hindpaw. Withdrawal responses to mechanical and heat stimulation and oedema levels were evaluated at 3, 6 and 24 h post-carrageenan injection. 3. The results showed that the inflammatory effect of 1% carrageenan peaked after 6 h with bilateral decreases in withdrawal latencies and ipsilateral oedema formation. 4. Contralateral treatment with 0.01, 0.05, 0.3 and 2 mg of U-50,488H attenuated nociceptive reflexes to mechanical stimulation on the inflamed side at 6 h. The anti-nociceptive effect of contralateral treatment was dose-dependent at 3 and 24 h. The hindpaw withdrawal latencies to heat stimulation were prolonged at 3 and 24 h after contralateral treatment with 0.3 mg U-50,488H. No effect on inflammatory oedema formation was observed, except for a decrease at 3 h after treatment with 2 mg of U-50,488H. 5. Sciatic nerve denervation on the contralateral side abolished the anti-nociceptive effects of U-50,488H (0.3 and 2 mg). In contrast, contralateral injection of 1 mg morphine prolonged paw latencies in denervated rats. 6. Both co-administration of the peripherally selective opioid antagonist naloxone methiodide with 0.3 mg U-50,488H, and alternatively, systemic administration of 0.3 mg U-50,488H reversed the anti-nociceptive effects induced by contralateral injection of U-50,488H. 7. Taken together, our findings indicate that the contralateral administration of U-50,488H attenuates nociceptive behaviour resulting from acute inflammation. The effect is mediated via peripheral neuronal kappa-opioid receptors and, possibly, spinal cord mechanisms, suggesting a new treatment approach for acute inflammatory conditions.
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, 171 77 Stockholm, Sweden. Indre.Bileviciute@fyfa.ki.se
authors.forename: I
authors.initials: I
authors.lastname: Bileviciute-Ljungar
authors.forename: M
authors.initials: M
authors.lastname: Spetea
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000208:Acute Disease; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003714:Denervation; D006614:Hindlimb / Q000473:pathology; D006358:Hot Temperature; D007249:Inflammation / Q000139:chemically induced / Q000150:complications* / Q000473:pathology; D008297:Male; D009270:Naloxone / Q000031:analogs & derivatives* / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement; D010812:Physical Stimulation; D000644:Quaternary Ammonium Compounds; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D012584:Sciatic Nerve
chemical_list: D000701:Analgesics, Opioid; D000644:Quaternary Ammonium Compounds; D017473:Receptors, Opioid, kappa; D009270:Naloxone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C041269:N-methylnaloxone