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N-Palmitoylethanolamide enhances antinociceptive effect of tramadol in neuropathic rats.
Biomed Pharmacother
December 2024
Laboratory 7, "Pain and Analgesia", Department of Pharmacobiology, Center for Research and Advanced Studies (CINVESTAV), Sede Sur, Mexico City, Mexico.
The efficacy of opioids in the treatment of chronic pain is limited; however, the adverse effects they produce are considerable. N-palmitoylethanolamide (PEA), a bioactive lipid mediator with structural similarities to endocannabinoids, has exhibited notable anti-inflammatory and analgesic effects in preclinical models. The objective of this study was to investigate the antinociceptive properties, motor coordination (MC), and constipation effects of tramadol and PEA in combination within a neuropathic pain model.
View Article and Find Full Text PDFDysfunctional S1P/S1PR1 signaling in the dentate gyrus drives vulnerability of chronic pain-related memory impairment.
Elife
December 2024
Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China.
Memory impairment in chronic pain patients is substantial and common, and few therapeutic strategies are available. Chronic pain-related memory impairment has susceptible and unsusceptible features. Therefore, exploring the underlying mechanisms of its vulnerability is essential for developing effective treatments.
View Article and Find Full Text PDFLipid raft disruption inhibits the activation of Transient Receptor Potential Vanilloid 1, but not TRP Melastatin 3 and the voltage-gated L-type calcium channels in sensory neurons.
Front Cell Dev Biol
November 2024
Department of Pharmacology and Pharmacotherapy, Medical School and Centre for Neuroscience, University of Pécs, Pécs, Hungary.
Transient Receptor Potential (TRP) ion channels like Vanilloid 1 (TRPV1) and Melastatin 3 (TRPM3) are nonselective cation channels expressed in primary sensory neurons and peripheral nerve endings, which are located in cholesterol- and sphingolipid-rich membrane lipid raft regions and have important roles in pain processing. Besides TRP ion channels a wide variety of voltage-gated ion channels were also described in the membrane raft regions of neuronal cells. Here we investigated the effects of lipid raft disruption by methyl-beta-cyclodextrin (MCD) and sphingomyelinase (SMase) on TRPV1, TRPM3 and voltage-gated L-type Ca channel activation in cultured trigeminal neurons and sensory nerve terminals of the trachea.
View Article and Find Full Text PDFInteraction between the dopaminergic and endocannabinoid systems promotes peripheral antinociception.
Eur J Pharmacol
January 2025
Laboratory of Pain and Analgesia, Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil. Electronic address:
Background: Dopamine has been widely related to pain modulation, at central and peripheral levels. In this study we aimed to investigate the mechanisms involved in peripheral antinociception, evaluating the interaction between the dopaminergic and endocannabinoid systems in this event.
Methods: Male Swiss mice (30-40 g) were pre-sensitized by administration of the hyperalgesic PGE (2 μg/paw).
Elevating levels of the endocannabinoid 2-arachidonoylglycerol blunts opioid reward but not analgesia.
Sci Adv
November 2024
Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10065, USA.
Article Synopsis
- Research shows that the endocannabinoid (eCB) system could be a target for new treatments to complement opioid therapies.
- Enhancing levels of 2-arachidonoylglycerol (2-AG) through a specific enzyme inhibitor in mice reduces the rewarding effects of opioids without affecting their pain-relieving abilities.
- The research indicates that these effects are linked to cannabinoid receptor 1 (CB1R) in a certain brain area, suggesting that boosting 2-AG could help in treating opioid addiction while maintaining pain management.
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