Research article summary (published 29 Sep 2009):

The peripheral antinociceptive effects of endomorphin-1 and kynurenic acid in the rat inflamed joint model.

Full Abstract

BACKGROUND: Several data suggest that both opioid and N-methyl-d-aspartate (NMDA) receptors are localized at the peripheral level, and drugs acting on these receptors may produce antinociception after topical administration; however, the antinociceptive effect of endogenous ligands at these receptors is poorly clarified. Our goal in this study was to determine the antinociceptive potency of the endogenous opioid peptide, endomorphin-1 (EM1), and the endogenous NMDA receptor antagonist, kynurenic acid (KYNA), and their interaction at the peripheral level in the rat inflamed joint model. METHODS: Mechanical hypersensitivity was produced by injection of carrageenan (300 microg/20 microL) into the tibiotarsal joint of the right hind leg. The mechanical pain threshold was assessed by von Frey filaments (0.064-110 g). EM1 (30, 100, and 200 microg), KYNA (30, 100, 200, and 400 microg), and their combinations in a fixed-dose ratio (1:1) were injected into the inflamed joint, and the pain threshold was determined repeatedly for 75 min after the drug administrations. RESULTS: Neither EM1 nor KYNA administered to the inflamed joint influenced the pain threshold at the noninflamed side. Both ligands produced dose-dependent antihyperalgesia, and the highest doses caused a prolonged effect. EM1 had higher potency (30% effective dose [ED(30)] and 50% effective dose [ED(50)] values were 112 microg [confidence interval {CI}: 80-146] and 167 microg [CI: 135-220], respectively) compared with KYNA (ED(30) and ED(50) values were 204 microg [CI: 160-251] and 330 microg [CI: 280-407], respectively). The antinociceptive effect of EM1 was prevented by subcutaneous naltrexone pretreatment. The coadministration of EM1 with KYNA caused an enhanced and/or prolonged antinociceptive effect. The ED(30) and ED(50) values of the combination were 141 microg [CI: 83-182] and 231 microg [CI: 190-293], respectively, which did not differ significantly from the theoretically additive values (ED(30) and ED(50) values were 145 microg [CI: 68-237] and 220 microg [CI: 144-230], respectively), thus the interaction between these ligands is additive. None of the treatments caused any sign of side effects. CONCLUSION: Peripherally administered endogenous opioid agonist and NMDA receptor antagonist ligands might be beneficial in inflammatory pain. Because both drugs barely cross the blood-brain barrier, their local administration causes no central side effects.

Author information

Author/s: Mecs, Laszlo (L); Tuboly, Gabor (G); Nagy, Endre (E); Benedek, Gyorgy (G); Horvath, Gyongyi (G);

Affiliation: Department of Orthopedics, University of Szeged, Szeged, Hungary.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Anesthesia and analgesia (Anesth Analg), published in United States. (Language: eng)

Reference: 2009-Oct; vol 109 (issue 4) : pp 1297-304

Dates: Created 2009/09/18; Completed 2009/10/01;

PMID: 19762760, status: MEDLINE (last retrieval date: 10/1/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Analgesics, Opioid - administration & dosage Animals Arthralgia - etiology; metabolism; physiopathology; prevention & control Arthritis, Experimental - chemically induced; complications; drug therapy; metabolism; physiopathology Behavior, Animal - drug effects Carrageenan Dose-Response Relationship, Drug Drug Therapy, Combination Edema - etiology Excitatory Amino Acid Antagonists - administration & dosage Hyperalgesia - etiology; metabolism; physiopathology; prevention & control Injections, Intra-Articular Injections, Subcutaneous

Kynurenic Acid - administration & dosage Ligands Male Naltrexone - administration & dosage Narcotic Antagonists - administration & dosage Oligopeptides - administration & dosage Pain Measurement Pain Threshold - drug effects Rats Rats, Wistar Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; metabolism Receptors, Opioid - agonists; metabolism Time Factors

Associated Chemicals: Analgesics, Opioid (0) ; Excitatory Amino Acid Antagonists (0) ; Ligands (0) ; Narcotic Antagonists (0) ; Oligopeptides (0) ; Receptors, N-Methyl-D-Aspartate (0) ; Receptors, Opioid (0) ; endomorphin 1 (0) ; Naltrexone (16590-41-3) ; Kynurenic Acid (492-27-3) ; Carrageenan (9000-07-1)

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