ANTINOCICEPTIVE INTERACTIONS BETWEEN ANANDAMIDE AND ENDOMORPHIN‐1 AT THE SPINAL LEVEL
Abstract
SUMMARY: 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.
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In preclinical models of acute pain, cannabinoid receptor agonists augment the antinociceptive effects of opioids.
“Cannabinoid receptor agonists augment the antinociceptive effects of opioids in preclinical models of acute pain, suggesting that cannabinoid agonists are opioid-sparing (Mecs et al, 2010;Tham et al, 2005;Tuboly et al, 2009).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Tuboly et al, 2009
Intrathecal co-administration of the endogenous opioid peptide endomorphin-1 (EM-1) and the endocannabinoid AEA reverses carrageenan-induced thermal hyperalgesia.
“Intrathecal co-administration of the endogenous opioid peptide endomorphin-1 (EM-1) and the endocannabinoid AEA reverses carrageenan-induced thermal hyperalgesia, suggesting a spinal site of action (Tuboly et al, 2009).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Tuboly et al, 2009
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Donvito, G., Nass, S. R., Wilkerson, J. L., Curry, Z. A., Schurman, L. D., Kinsey, S. G., & Lichtman, A. H. (2018) · Neuropsychopharmacology · doi:10.1038/npp.2017.204 · Cited by 301 · see citing works
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Self-citation
- Authors
- Tuboly, G., Mecs, L., Benedek, G., & Horvath, G.
- Affiliations
- University of Szeged (HU)
- Venue
- Clinical and Experimental Pharmacology and Physiology
- Publisher
- Wiley
- Published
- 2009-03-26
- Volume
- 36
- Issue
- 4
- Pages
- 400-405
- ISSN
- 0305-1870 (ISSN-L)
- 1440-1681
- OpenAlex
- W2129278228
- Cited by
- 14
- References
- 46
- Citations by year
- 2022: 1 · 2017: 2 · 2014: 1 · 2013: 2 · 2012: 1
- FWCI
- 1.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical and Experimental Pharmacology and Physiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- anandamide, endomorphin-1, antinociception, CB1 receptor, mu-opioid receptor, opioid-cannabinoid interaction, synergistic analgesia, carrageenan-induced hyperalgesia, intrathecal administration, thermal hyperalgesia, endocannabinoids
- MeSH terms
- Analgesics, Animals, Arachidonic Acids, Carrageenan, Drug Combinations, Drug Interactions, Drug Evaluation, Preclinical, Hyperalgesia, Inflammation, Injections, Spinal, Male, Oligopeptides, Pain, Spine, Time Factors, Rats, Wistar, Rats, Polyunsaturated Alkamides, Endocannabinoids
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