ArticleBritish journal of pharmacology2011
Capsaicin in the periaqueductal gray induces analgesia via metabotropic glutamate receptor-mediated endocannabinoid retrograde disinhibition.
Article in British journal of pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 56 citations in OpenAlex.
- Article
- A comprehensive review of capsaicin: Biosynthesis, industrial productions, processing to applications, and clinical uses.Heliyon · 2024Review
- Selective activation of AKAP150/TRPV1 in ventrolateral periaqueductal gray GABAergic neurons facilitates conditioned place aversion in male mice.Communications biology · 2023Article
- Endocannabinoids at the synapse and beyond: implications for neuropsychiatric disease pathophysiology and treatment.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Review
- An Updated Review on the Metabolite (AM404)-Mediated Central Mechanism of Action of Paracetamol (Acetaminophen): Experimental Evidence and Potential Clinical Impact.Journal of pain research · 2023Review
- Cannabinoids and Opioids Differentially Target Extrinsic and Intrinsic GABAergic Inputs onto the Periaqueductal Grey Descending Pathway.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- TRPV1: A Common Denominator Mediating Antinociceptive and Antiemetic Effects of Cannabinoids.International journal of molecular sciences · 2022Review
- Bioflavonoid exerts analgesic and anti-inflammatory effects via transient receptor potential 1 channel in a rat model.Arquivos de neuro-psiquiatria · 2022Article
- Supraspinal Mechanisms of Intestinal Hypersensitivity.Cellular and molecular neurobiology · 2022Review
- Cellular and circuit diversity determines the impact of endogenous opioids in the descending pain modulatory pathway.Frontiers in systems neuroscience · 2022Review
- Synthesis, Antibacterial and Insecticidal Activities of Novel Capsaicin Derivatives Containing a Sulfonic Acid Esters Moiety.Frontiers in chemistry · 2022Article
- Paracetamol is a centrally acting analgesic using mechanisms located in the periaqueductal grey.British journal of pharmacology · 2020Article
- DAGLα Inhibition as a Non-invasive and Translational Model of Episodic Headache.Frontiers in pharmacology · 2020Article
- Distal Electroacupuncture at the LI4 Acupoint Reduces CFA-Induced Inflammatory Pain via the Brain TRPV1 Signaling Pathway.International journal of molecular sciences · 2019Article
- Capsaicin induces apoptosis and autophagy in human melanoma cells.Oncology letters · 2019Article
- Inhibition of GABAergic Neurons and Excitation of Glutamatergic Neurons in the Ventrolateral Periaqueductal Gray Participate in Electroacupuncture Analgesia Mediated by Cannabinoid Receptor.Frontiers in neuroscience · 2019Article
- The Endocannabinoid Reuptake Inhibitor WOBE437 Is Orally Bioavailable and Exerts Indirect Polypharmacological Effects via Different Endocannabinoid Receptors.Frontiers in molecular neuroscience · 2018Article
- Role of Autophagy in Capsaicin-Induced Apoptosis in U251 Glioma Cells.Cellular and molecular neurobiology · 2016Article
- Capsaicin: Current Understanding of Its Mechanisms and Therapy of Pain and Other Pre-Clinical and Clinical Uses.Molecules (Basel, Switzerland) · 2016Review
- Emerging Role of Spinal Cord TRPV1 in Pain Exacerbation.Neural plasticity · 2016Review
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 purposeCapsaicin, an agonist of transient receptor potential vanilloid 1 (TRPV1) channels, is pro-nociceptive in the periphery but is anti-nociceptive when administered into the ventrolateral periaqueductal gray (vlPAG), a midbrain region for initiating descending pain inhibition. Here, we investigated how activation of TRPV1 channels in the vlPAG leads to anti-nociception. EXPERIMENTAL APPROACH: We examined synaptic transmission and neuronal activity using whole-cell recordings in vlPAG slices in vitro and hot-plate nociceptive responses in rats after drug microinjection into the vlPAG in vivo. KEY
resultsCapsaicin (1-10 µM) depressed evoked GABAergic inhibitory postsynaptic currents (eIPSCs) in vlPAG slices presynaptically, while increasing miniature excitatory PSC frequency. Capsaicin-induced eIPSC depression was antagonized by cannabinoid CB₁ and metabotropic glutamate (mGlu₅) receptor antagonists, and prevented by inhibiting diacylglycerol lipase (DAGL), which converts DAG into 2-arachidonoylglycerol (2-AG), an endocannabinoid. Capsaicin induced membrane depolarization in 2/3 neurons recorded but, overall, increased neuronal firings by increasing evoked postsynaptic potentials. Intra-vlPAG capsaicin reduced hot-plate responses in rats, effects blocked by CB₁ and mGlu receptor antagonists. Effects of capsaicin were antagonized by SB 366791, a TRPV1 channel antagonist. CONCLUSIONS AND IMPLICATIONS: Capsaicin activated TRPV1s on glutamatergic terminals to release glutamate which activated postsynaptic mGlu₅ receptors, yielding 2-AG from DAG by DAGL hydrolysis. 2-AG induces retrograde inhibition (disinhibition) of GABA release via presynaptic CB₁ receptors. This disinhibition in the vlPAG leads to anti-nociception by activating the descending pain inhibitory pathway. This is a novel TRPV1 channel-mediated anti-nociceptive mechanism in the brain and a new interaction between vanilloid and endocannabinoid systems.
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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.