Peripheral antinociceptive effect of 2‐arachidonoyl‐glycerol and its interaction with endomorphin‐1 in arthritic rat ankle joints
Abstract
Summary: 1. Both cannabinoid and opioid receptors are localized at the peripheral level, and drugs acting on these receptors may produce antinociception after topical administration; however, the effect of endogenous ligands at these receptors is poorly understood. Our goal was to determine the antinociceptive potency of the endogenous cannabinoid 2‐arachidonoyl‐glycerol (2‐AG), and its interaction with endomorphin‐1 (EM1) at joint level in the rat inflammation model. 2. Mechanical hypersensitivity was produced by injection of carrageenan (300 μg/30 μL) into the tibiotarsal joint of the right hind leg. The mechanical threshold was assessed by von Frey filaments. 2‐AG (3–200 μg), EM1 (100–300 μg) and their combinations in a fixed‐dose ratio (1 : 10) were given into the inflamed joint, and the threshold was determined repeatedly for 105 min after the drug administrations. 3. Both ligands produced dose‐dependent anti‐hyperalgesia, and the highest doses caused prolonged effects, but they did not influence the degree of oedema and the withdrawal threshold at the non‐inflamed side. EM1 had lower potency compared to 2‐AG (ED 25: 233 (CI: 198–268) μg and 126 (CI: 88–162) μg, respectively;P < 0.05). The effects of EM1 and 2‐AG were prevented by μ‐opioid and cannabinoid 1 receptor antagonists, respectively. The ED 25 value for the combination (98 (CI: 80–112) μg) did not differ significantly from the value of 2‐AG; however, the largest dose combination produced a significantly higher effect than the ligands by themselves. 4. Our data showed that 2‐AG was an effective antinociceptive ligand at joint level, and its combination with EM1 produced long‐lasting, effective antinociception.
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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 Mecs et al, 2010
Combined peripheral administration of EM-1 and 2-AG attenuates mechanical allodynia produced by intra-articular injection of carrageenan, but does not affect edema.
“Combined peripheral administration of the endogenous opioid peptide EM-1 and the endocannabinoid 2-AG attenuates mechanical allodynia produced by intra-articular injection of carrageenan, but did not affect edema (Mecs et al, 2010).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Mecs et al, 2010
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- Authors
- Mecs, L., Tuboly, G., Toth, K., Nagy, E., Nyari, T., Benedek, G., & Horvath, G.
- Affiliations
- University of Szeged (HU)
- ORCID
- Nagy, Endre
- Venue
- Clinical and Experimental Pharmacology and Physiology
- Publisher
- Wiley
- Published
- 2010-04-16
- Volume
- 37
- Issue
- 5-6
- Pages
- 544-550
- ISSN
- 0305-1870 (ISSN-L)
- 1440-1681
- OpenAlex
- W2006313093
- Cited by
- 16
- References
- 56
- Citations by year
- 2023: 1 · 2022: 1 · 2019: 2 · 2017: 3 · 2016: 1 · 2015: 1 · 2014: 1 · 2012: 3
- FWCI
- 1.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical and Experimental Pharmacology and Physiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- 2-arachidonoylglycerol, endomorphin-1, antinociception, peripheral cannabinoid receptors, mu-opioid receptor, opioid-cannabinoid interaction, carrageenan-induced arthritis, ankle joint inflammation, mechanical hypersensitivity, cannabinoid 1 receptor, mu-opioid receptor antagonist, topical analgesia
- MeSH terms
- Analgesics, Opioid, Animals, Arachidonic Acids, Arthritis, Experimental, Dose-Response Relationship, Drug, Drug Synergism, Edema, Glycerides, Ligands, Male, Narcotic Antagonists, Oligopeptides, Receptors, Opioid, Tarsal Joints, Rats, Wistar, Pain Threshold, Receptors, Cannabinoid, Rats, Cannabinoid Receptor Modulators, Endocannabinoids
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