title: Systemic synergism between codeine and morphine in three pain models in mice.
abstract: BACKGROUND
  The combination of two analgesic agents offers advantages in pain treatment. Codeine and morphine analgesia is due to activation of opioid receptor subtypes.
  
  
  METHODS
  This study, performed in mice using isobolographic analysis, evaluated the type of interaction in intraperitoneal (ip) or intrathecal (it) coadministration of codeine and morphine, in three nociceptive behavioral models.
  
  
  RESULTS
  Intrathecal morphine resulted to be 7.5 times more potent than ip morphine in the writhing test, 55.6 times in the tail flick test and 1.7 times in phase II of the orofacial formalin test; however, in phase I of the same test ip was 1.2 times more potent than it morphine. Intrathecal codeine resulted being 3.4 times more potent than ip codeine in the writhing test, 1.6 times in the tail flick test, 2.5 times in phase I and 6.7 times in phase II of the orofacial formalin test. Opioid coadministration had a synergistic effect in the acute tonic pain (acetic acid writhing test), acute phasic pain (tail flick test) and inflammatory pain (orofacial formalin test). The interaction index ranged between 0.284 (writhing ip) and 0.440 (orofacial formalin phase II ip).
  
  
  CONCLUSIONS
  This synergy may relate to the different pathways of pain transmission and to the different intracellular signal transduction. The present findings also raise the possibility of potential clinical advantages in combining opioids in pain management.
authors.affiliation: Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Medical School, University of Chile, and Cardiovascular Department, Clinical Hospital, Santiago, Chile. hmiranda@med.uchile.cl
authors.forename: Hugo F
authors.initials: HF
authors.lastname: Miranda
authors.forename: Viviana
authors.initials: V
authors.lastname: Noriega
authors.forename: Ramiro J
authors.initials: RJ
authors.lastname: Zepeda
authors.forename: Fernando
authors.initials: F
authors.lastname: Sierralta
authors.forename: Juan C
authors.initials: JC
authors.lastname: Prieto
mesh_terms: D019342:Acetic Acid / Q000633:toxicity; D059787:Acute Pain / Q000188:drug therapy; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003061:Codeine / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004357:Drug Synergism; D005557:Formaldehyde / Q000633:toxicity; D007249:Inflammation / Q000188:drug therapy; D007274:Injections, Intraperitoneal; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000701:Analgesics, Opioid; D005557:Formaldehyde; D009020:Morphine; D019342:Acetic Acid; D003061:Codeine