title: Antinociceptive synergy between diclofenac and morphine after local injection into the inflamed site.
abstract: BACKGROUND
  Combinations of non-steroidal anti-inflammatory drugs with opioids are frequently used to reduce opioid doses required in the clinical management of acute pain. The present study was designed to evaluate the possible antinociceptive interaction between morphine and diclofenac at peripheral level in male rats.
  
  
  METHODS
  Drugs were chosen based on their efficacy in the treatment of this kind of pain and as representative drugs of their respective analgesic groups. For the formalin test, 50 μ of 1% formalin solution was injected subcutaneously into the right hind paw. The interaction between morphine and diclofenac was evaluated by using isobolographic analysis and interaction index. Drug interaction was examined by administering fixed-ratio combinations of morphine-diclofenac (1 : 1 and 3 : 1) of their respective ED30 fractions.
  
  
  RESULTS
  Diclofenac and morphine reduced flinching behavior in a dose-dependent manner during phase 2 but not phase 1 of the formalin test. Isobolographic analysis showed a synergistic interaction for the combination of morphine and diclofenac after local peripheral administration.
  
  
  CONCLUSIONS
  Data suggest that the combination of morphine with diclofenac at the site of injury is synergistic and could be useful in the treatment of wounds, bruises, rheumatisms and other painful peripheral conditions associated with an inflammatory process.
authors.affiliation: Pain Mechanisms Laboratory, Research Center of the Academic Division of Health Sciences, Juarez Autonomous University of Tabasco, Villahermosa Tabasco, México. jorge.torres@ujat.mx
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Torres-López
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Carmona-Díaz
authors.forename: José L
authors.initials: JL
authors.lastname: Cortés-Peñaloza
authors.forename: Crystell G
authors.initials: CG
authors.lastname: Guzmán-Priego
authors.forename: Héctor I
authors.initials: HI
authors.lastname: Rocha-González
mesh_terms: D059787:Acute Pain / Q000188:drug therapy*; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D004008:Diclofenac / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005557:Formaldehyde; D007267:Injections; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac; D005557:Formaldehyde; D009020:Morphine