ArticleFrontiers in pain research (Lausanne, Switzerland)2023
ABHD6 and MAGL control 2-AG levels in the PAG and allodynia in a CSD-induced periorbital model of headache.
Article in Frontiers in pain research (Lausanne, Switzerland), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- A systematic review of the causes and consequences of spreading depolarization in neuroinflammation; implications for neurovascular disorders.Journal of neuroinflammation · 2025Pooled it
- Ibogalogs reduce acute and chronic headache-like behaviours in rodents by different co-modulatory mechanisms involving 5-HTResearch square · 2026Article
- The Phospholipase AJournal of lipid and atherosclerosis · 2026Review
- Temporal multi-omic exploration of the ventral tegmental area in chronic pain and passive coping behaviors.iScience · 2026Article
- PN6047 Demonstrates Broad Preclinical Efficacy in Headache Models as a Novel Delta-Opioid Receptor Agonist.bioRxiv : the preprint server for biology · 2026Article
- Glucocorticoid-endocannabinoid crosstalk in the ventrolateral periaqueductal gray (vlPAG) promotes pain resolution.bioRxiv : the preprint server for biology · 2026Article
- Distribution and subacute modulation of endocannabinoid metabolizing enzymes in the trigeminal complex and midbrain in a pre-clinical model of post-traumatic headache.The journal of headache and pain · 2026Article
- Overlapping pathways of migraine and the endocannabinoid system: Potential therapeutic targets.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Endocannabinoid Modulation in Headache: Mechanisms, Models, and Translational Therapies.Cells · 2026Review
- Brain Hsp90 Inhibition Mitigates Facial Allodynia in a Rat Model of CSD Headache and Upregulates Endocannabinoid Signaling in the PAG.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Corticosterone stimulates synthesis of 2-arachidonoylglycerol via putative membrane-bound glucocorticoid receptors and inhibits GABA release via CB1 cannabinoid receptors in the ventrolateral periaqueductal gray.Molecular pharmacology · 2025Article
- Inhibition of endocannabinoid hydrolases MAGL, FAAH and ABHD6 by AKU-005 reduces ex vivo cortical spreading depression.The journal of headache and pain · 2025Article
- Enhancement of the endocannabinoid system through monoacylglycerol lipase inhibition relieves migraine-associated pain in mice.The journal of headache and pain · 2025Article
- Inhibition of diacylglycerol lipase α induced blood-brain barrier breach in female Sprague-Dawley rats.The Journal of physiology · 2025Article
- Sex differences in photophobic behaviors following cortical spreading depression in rats.Cephalalgia : an international journal of headache · 2025Article
- Formoterol dynamically alters endocannabinoid tone in the periaqueductal gray inducing headache.The journal of headache and pain · 2024Article
- Analgesic Properties of Next-Generation Modulators of Endocannabinoid Signaling: Leveraging Modern Tools for the Development of Novel Therapeutics.The Journal of pharmacology and experimental therapeutics · 2024Review
- Inhibition of 2-AG hydrolysis alleviates posttraumatic headache attributed to mild traumatic brain injury.The journal of headache and pain · 2024Article
- Effects of the Dual FAAH/MAGL Inhibitor AKU-005 on Trigeminal Hyperalgesia in Male Rats.Cells · 2024Article
- Depletion of Endothelial-Derived 2-AG Reduces Blood-Endothelial Barrier Integrity via Alteration of VE-Cadherin and the Phospho-Proteome.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Introduction: The high prevalence and severe symptoms of migraines in humans emphasizes the need to identify underlying mechanisms that can be targeted for therapeutic benefit. Clinical Endocannabinoid Deficiency (CED) posits that reduced endocannabinoid tone may contribute to migraine development and other neuropathic pain conditions. While strategies that increase levels of the endocannabinoid n-arachidonoylethanolamide have been tested, few studies have investigated targeting the levels of the more abundant endocannabinoid, 2-arachidonoylgycerol, as an effective migraine intervention. Methods: Cortical spreading depression was induced in female Sprague Dawley rats via KCl (potassium chloride) administration, followed by measures of endocannabinoid levels, enzyme activity, and neuroinflammatory markers. Efficacy of inhibiting 2-arachidonoylglycerol hydrolysis to mitigate periorbital allodynia was then tested using reversal and prevention paradigms. Results: We discovered reduced 2-arachidonoylglycerol levels in the periaqueductal grey associated with increased hydrolysis following headache induction. Pharmacological inhibition of the 2-arachidonoylglycerol hydrolyzing enzymes, Discussion: Our study unravels a mechanistic link between 2-arachidonoylglycerol hydrolysis activity in the periaqueductal grey in a preclinical, rat model of migraine. Thus, 2-arachidonoylglycerol hydrolysis inhibitors represent a potential new therapeutic avenue for the treatment of headache.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.