title: Isobolographic analysis of the opioid-opioid interactions in a tonic and a phasic mouse model of induced nociceptive pain.
abstract: BACKGROUND
  Opioids have been used for the management of pain and coadministration of two opioids may induce synergism. In a model of tonic pain, the acetic acid writhing test and in a phasic model, the hot plate, the antinociceptive interaction between fentanyl, methadone, morphine, and tramadol was evaluated.
  
  
  RESULTS
  The potency of opioids in the writhing test compared to the hot plate assay was from 2.5 (fentanyl) to 15.5 (morphine) times, respectively. The ED50 was used in a fixed ratio for each of the six pairs of opioid combinations, which, resulted in a synergistic antinociception except for methadone/tramadol and fentanyl/tramadol which were additive, in the hot plate. The opioid antagonists naltrexone, naltrindole and nor-binaltorphimine, suggests that the synergism of morphine combinations are due to the activation of MOR subtypes with partially contribution of DOR and KOR, however fentanyl and methadone combinations are partially due to the activation of MOR and DOR subtypes and KOR lack of participation. The antinociceptive effects of tramadol combinations, are partially due to the activation of MOR, DOR and KOR opioid subtypes.
  
  
  CONCLUSIONS
  These results suggets that effectiveness and magnitude of the interactions between opioids are dependent on pain stimulus intensity.
authors.forename: Hugo F
authors.initials: HF
authors.lastname: Miranda
authors.forename: Viviana
authors.initials: V
authors.lastname: Noriega
authors.forename: Pilar
authors.initials: P
authors.lastname: Zanetta
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Prieto
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Prieto-Rayo
authors.forename: Nicolás
authors.initials: N
authors.lastname: Aranda
authors.forename: Fernando
authors.initials: F
authors.lastname: Sierralta
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004357:Drug Synergism; D005283:Fentanyl / Q000819:agonists / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009020:Morphine / Q000819:agonists / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology; D059226:Nociceptive Pain / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology; D011957:Receptors, Opioid / Q000378:metabolism*
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D009020:Morphine; D005283:Fentanyl