ArticleBritish journal of pharmacology2014
Endocannabinoid modulation by FAAH and monoacylglycerol lipase within the analgesic circuitry of the periaqueductal grey.
Article in British journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Glucocorticoid-endocannabinoid crosstalk in the ventrolateral periaqueductal gray (vlPAG) promotes pain resolution.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Glucocorticoid-endocannabinoid crosstalk in the ventrolateral periaqueductal gray (vlPAG) promotes pain resolution.bioRxiv : the preprint server for biology · 2026Article
- Overlapping pathways of migraine and the endocannabinoid system: Potential therapeutic targets.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Article
- The Endocannabinoid-Microbiota-Neuroimmune Super-System: A Unifying Feedback Architecture for Systems Resilience, Collapse Trajectories, and Precision Feedback Medicine.International journal of molecular sciences · 2025Review
- 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
- Molecular basis of FAAH-OUT-associated human pain insensitivity.Brain : a journal of neurology · 2023Article
- Monoacylglycerol Lipase Protects the Presynaptic Cannabinoid 1 Receptor from Desensitization by Endocannabinoids after Persistent Inflammation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Release of Endocannabinoids into the Cerebrospinal Fluid during the Induction of the Trigemino-Hypoglossal Reflex in Rats.Current issues in molecular biology · 2022Article
- Effect of Fatty Acid Amide Hydrolase Inhibitor URB597 on Orofacial Pain Perception in Rats.International journal of molecular sciences · 2022Article
- DAGLα Inhibition as a Non-invasive and Translational Model of Episodic Headache.Frontiers in pharmacology · 2020Article
- Irritable Bowel Syndrome: Manipulating the Endocannabinoid System as First-Line Treatment.Frontiers in neuroscience · 2020Article
- The Endocannabinoid Reuptake Inhibitor WOBE437 Is Orally Bioavailable and Exerts Indirect Polypharmacological Effects via Different Endocannabinoid Receptors.Frontiers in molecular neuroscience · 2018Article
- Potential of Endocannabinoids to Control Bladder Pain.Frontiers in systems neuroscience · 2018Review
- Effects of centrally administered endocannabinoids and opioids on orofacial pain perception in rats.British journal of pharmacology · 2017Article
- Endocannabinoids control vesicle release mode at midbrain periaqueductal grey inhibitory synapses.The Journal of physiology · 2017Article
- The Role of the Endocannabinoid System in the Brain-Gut Axis.Gastroenterology · 2016Review
- Anandamide in the dorsal periaqueductal gray inhibits sensory input without a correlation to sympathoexcitation.Neurobiology of pain (Cambridge, Mass.)Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeEndogenous cannabinoids (endocannabinoids) in the periaqueductal grey (PAG) play a vital role in mediating stress-induced analgesia. This analgesic effect of endocannabinoids is enhanced by pharmacological inhibition of their degradative enzymes. However, the specific effects of endocannabinoids and the inhibitors of their degradation are largely unknown within this pain-modulating region. EXPERIMENTAL APPROACH: In vitro electrophysiological recordings were conducted from PAG neurons in rat midbrain slices. The effects of the major endocannabinoids and their degradation inhibitors on inhibitory GABAergic synaptic transmission were examined. KEY
resultsExogenous application of the endocannabinoid, anandamide (AEA), but not 2-arachidonoylglycerol (2-AG), produced a reduction in inhibitory GABAergic transmission in PAG neurons. This AEA-induced suppression of inhibition was enhanced by the fatty acid amide hydrolase (FAAH) inhibitor, URB597, whereas a 2-AG-induced suppression of inhibition was unmasked by the monoacylglycerol lipase (MGL) inhibitor, JZL184. In addition, application of the CB1 receptor antagonist, AM251, facilitated the basal GABAergic transmission in the presence of URB597 and JZL184, which was further enhanced by the dual FAAH/MGL inhibitor, JZL195. CONCLUSIONS AND IMPLICATIONS: Our results indicate that AEA and 2-AG act via disinhibition within the PAG, a cellular action consistent with analgesia. These actions of AEA and 2-AG are tightly regulated by their respective degradative enzymes, FAAH and MGL. Furthermore, individual or combined inhibition of FAAH and/or MGL enhanced tonic disinhibition within the PAG. Therefore, the current findings support the therapeutic potential of FAAH and MGL inhibitors as a novel pharmacotherapy for pain.
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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.