title: The central versus peripheral antinociceptive effects of μ-opioid receptor agonists in the new model of rat visceral pain.
abstract: This study describes the antinociceptive effects of μ-opioid agonists, d-Ala(2),N-Me-Phe(4),Gly(5)-ol-enkephalin (DAMGO) and morphine in a model of rat visceral pain in which nociceptive responses were triggered by 2% acetic acid intraperitoneal (i.p.) injections. DAMGO and morphine were administered i.p., to the same site where acetic acid was delivered or intracerebroventricularly (i.c.v.). The antinociceptive actions of i.p. versus i.c.v. administered DAMGO or morphine were evaluated in the late phase of permanent visceral nociceptive responses. Both compounds inhibited the nociceptive responses in a dose-dependent manner and exhibited more potent agonist activity after i.c.v. than i.p. administration. DAMGO and morphine showed comparable ED(50) values after i.p. injections. However, DAMGO was much stronger than morphine after central administration. Co-administration of the peripherally restricted opioid antagonist, naloxone methiodide (NAL-M), significantly attenuated the antinociceptive effects of i.p. DAMGO or morphine. On the other hand, i.c.v. injections of NAL-M partially antagonized the antinociceptive effect of i.p. morphine and failed to affect the antinociceptive action of i.p. DAMGO indicating the partial and pure peripheral antinociceptive effects of morphine and DAMGO, respectively. These results suggest the role of either central or peripheral μ-opioid receptors (MOR) in mediating antinociceptive effects of i.p. μ-opioid agonists in the rat late permanent visceral pain model which closely resembles the clinical situation.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4, P.O. Box 370, H-1445 Budapest, Hungary.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Al-Khrasani
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Lackó
authors.forename: Pál
authors.initials: P
authors.lastname: Riba
authors.forename: Kornél
authors.initials: K
authors.lastname: Király
authors.forename: Melinda
authors.initials: M
authors.lastname: Sobor
authors.forename: Júlia
authors.initials: J
authors.lastname: Timár
authors.forename: Shaaban
authors.initials: S
authors.lastname: Mousa
authors.forename: Michael
authors.initials: M
authors.lastname: Schäfer
authors.forename: Susanna
authors.initials: S
authors.lastname: Fürst
mesh_terms: D019342:Acetic Acid / Q000633:toxicity; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004347:Drug Interactions; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000627:therapeutic use*; D009020:Morphine / Q000627:therapeutic use*; D009270:Naloxone / Q000008:administration & dosage / Q000031:analogs & derivatives; D009292:Narcotic Antagonists / Q000008:administration & dosage; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage; D051381:Rats; D059265:Visceral Pain / Q000139:chemically induced / Q000188:drug therapy*
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D000644:Quaternary Ammonium Compounds; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; C041269:N-methylnaloxone; D009020:Morphine; D019342:Acetic Acid