ArticleProceedings of the National Academy of Sciences of the United States of America2006
The cannabinoid WIN 55,212-2 inhibits transient receptor potential vanilloid 1 (TRPV1) and evokes peripheral antihyperalgesia via calcineurin.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 157 citations in OpenAlex.
- FABP5 deletion in nociceptors augments endocannabinoid signaling and suppresses TRPV1 sensitization and inflammatory pain.Scientific reports · 2022Trial
- The Pro- But Not Antinociceptive Effects of Cannabidiol Depend on Trpa1b in Larval Zebrafish.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Evaluating FABP5 as a Therapeutic Target for Pain Management.European journal of pain (London, England) · 2026Review
- The pro-, but not anti-nociceptive effects of Cannabidiol depend on Trpa1b in larval Zebrafish.bioRxiv : the preprint server for biology · 2025Article
- Oleic acid released by sensory neurons inhibits TRPV1-mediated thermal hypersensitivity via GPR40.iScience · 2024Article
- Cannabinoid Analgesia in Postoperative Pain Management: From Molecular Mechanisms to Clinical Reality.International journal of molecular sciences · 2024Review
- Adverse Ocular Impact and Emerging Therapeutic Potential of Cannabis and Cannabinoids: A Narrative Review.Clinical ophthalmology (Auckland, N.Z.) · 2024Review
- TRPV1: A Common Denominator Mediating Antinociceptive and Antiemetic Effects of Cannabinoids.International journal of molecular sciences · 2022Review
- Peripherally administered cannabinoid receptor 2 (CBBrain research · 2022Article
- TRP Channels as Molecular Targets to Relieve Cancer Pain.Biomolecules · 2021Review
- Lack of the Transient Receptor Potential Vanilloid 1 Shifts Cannabinoid-Dependent Excitatory Synaptic Plasticity in the Dentate Gyrus of the Mouse Brain Hippocampus.Frontiers in neuroanatomy · 2021Article
- Synthetic Cannabinoid Agonist WIN 55212-2 Targets Proliferation, Angiogenesis, and ApoptosisFrontiers in reproductive health · 2021Article
- Dose-Related Inhibition of Capsaicin Responses by Cannabinoids CBG, CBD, THC and their Combination in Cultured Sensory Neurons.Journal of pain research · 2021Article
- Inhibition of TRPV1 by SHP-1 in nociceptive primary sensory neurons is critical in PD-L1 analgesia.JCI insight · 2020Article
- CBBritish journal of pharmacology · 2020Article
- Cannabinoids as anticancer therapeutic agents.Cell cycle (Georgetown, Tex.) · 2020Review
- CBD Effects on TRPV1 Signaling Pathways in Cultured DRG Neurons.Journal of pain research · 2020Article
- Role of cannabinoid receptor 1 and the peroxisome proliferator-activated receptor α in mediating anti-nociceptive effects of synthetic cannabinoids and a cannabinoid-like compound.Inflammopharmacology · 2019Article
- TRP Channels as Novel Targets for Endogenous Ligands: Focus on Endocannabinoids and Nociceptive Signalling.Current neuropharmacology · 2018Review
- H89 dihydrochloride hydrate and calphostin C lower the body temperature through TRPV1.Molecular medicine reports · 2018Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
Cannabinoids can evoke antihyperalgesia and antinociception at a peripheral site of action. However, the signaling pathways mediating these effects are not clearly understood. We tested the hypothesis that certain cannabinoids directly inhibit peripheral capsaicin-sensitive nociceptive neurons by dephosphorylating and desensitizing transient receptor potential vanilloid 1 (TRPV1) via a calcium calcineurin-dependent mechanism. Application of the cannabinoid WIN 55,212-2 (WIN) to cultured trigeminal (TG) neurons or isolated skin biopsies rapidly and significantly inhibited capsaicin-activated inward currents and neuropeptide exocytosis by a mechanism requiring the presence of extracellular calcium. The inhibitory effect did not involve activation of G protein-coupled cannabinoid receptors, because neither pertussis toxin nor GDPbetaS treatments altered the WIN effect. However, application of WIN-activated calcineurin, as measured by nuclear translocation of the nuclear factor of activated T cells (NFAT)c4 transcription factor, dephosphorylated TRPV1. The WIN-induced desensitization of TRPV1 was mediated by calcineurin, because the application of structurally distinct calcineurin antagonists (calcineurin autoinhibitory peptide and cyclosporine/cyclophilin complex) abolished WIN-induced inhibition of capsaicin-evoked inward currents and neuropeptide exocytosis. This mechanism also contributed to peripheral antinociceptive/antihyperalgesic effects of WIN because pretreatment with the calcineurin antagonist calcineurin autoinhibitory peptide (CAIP) significantly reduced peripherally mediated WIN effects in two behavioral models. Collectively, these data demonstrate that cannabinoids such as WIN directly inhibit TRPV1 functional activities via a calcineurin pathway that represents a mechanism of cannabinoid actions at peripheral sites.
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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.