Antinociceptive interactions between anandamide and endomorphin-1 at the spinal level

Gabor Tuboly, Laszlo Mecs, György Benedek, Gyöngyi Horvath

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10 Citations (Scopus)


Although it is well known that the combined administration of synthetic or plant-originated opioids with cannabinoids (CB) results in synergistic antinociception, the effects of combined administration of endogenous ligands acting at μ-opioid and CB receptors are not known. The aim of the present study was to determine the interaction between anandamide (AEA; a CB 1 receptor agonist) and endomorphin-1 (EM-1; a μ-opioid receptor agonist) after intrathecal administration. Nociception was assessed by the paw-withdrawal test after carrageenan-induced inflammation in male Wistar rats. Endomorphin-1 (16.4 pmol to 16.4 nmol) and AEA (4.3-288 nmol) alone dose-dependently decreased carrageenan-induced thermal hyperalgesia, although the highest dose of AEA also exhibited pain-inducing potential. The potency of AEA was approximately 59-fold lower than that of EM-1 (35% effective dose (ED 35) 194.4 vs 3.3 nmol, respectively). Coadministration of these ligands revealed that combinations of 16.4 pmol EM-1 plus 28.8 or 86.5 nmol AEA were more effective than either drug alone, but other combinations were no more effective than the administration of EM-1 itself. Therefore, coadministration of AEA did not significantly shift the dose-response curve to EM-1. The results of the present study indicate that the coadministration of AEA and EM-1 results in potentiated antihyperalgesia only for a combination of specific doses. Because AEA activates other receptor types (e.g. TRPV1) in addition to CB 1 receptors, the results of the present suggest that, after the coadministration of EM-1 and AEA, complex interactions ensue that may lead to different outcomes compared with those seen following the injection of exogenous ligands.

Original languageEnglish
Pages (from-to)400-405
Number of pages6
JournalClinical and Experimental Pharmacology and Physiology
Issue number4
Publication statusPublished - Apr 1 2009



  • Anandamide
  • Cannabinoid
  • Endomorphin-1
  • Hyperalgesia
  • Interaction
  • Intrathecal
  • Pain

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

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