Systemic synergism between codeine and morphine in three pain models in mice

Hugo F. Miranda, Viviana Noriega, Ramiro J. Zepeda, Fernando Sierralta, Juan C. Prieto

Research output: Contribution to journalArticle

13 Citations (Scopus)

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). Conclusion: 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.

Original languageEnglish
Pages (from-to)80-88
Number of pages9
JournalPharmacological Reports
Volume65
Issue number1
DOIs
Publication statusPublished - 2013

Keywords

  • Algesiometer tests
  • Isobolographic analysis
  • Opioids
  • Synergism

ASJC Scopus subject areas

  • Pharmacology

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    Miranda, H. F., Noriega, V., Zepeda, R. J., Sierralta, F., & Prieto, J. C. (2013). Systemic synergism between codeine and morphine in three pain models in mice. Pharmacological Reports, 65(1), 80-88. https://doi.org/10.1016/S1734-1140(13)70966-6