ArticlePloS one2010
TRPV1 in brain is involved in acetaminophen-induced antinociception.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 165 citations in OpenAlex.
- Premedication with oral paracetamol for reduction of propofol injection pain: a randomized placebo-controlled trial.BMC anesthesiology · 2019Trial
- Pharmacokinetics of Oral and Intravenous Paracetamol (Acetaminophen) When Co-Administered with Intravenous Morphine in Healthy Adult Subjects.Clinical drug investigation · 2018Trial
- Paracetamol sharpens reflection and spatial memory: a double-blind randomized controlled study in healthy volunteers.Drug design, development and therapy · 2016Trial
- The brain signature of paracetamol in healthy volunteers: a double-blind randomized trial.Drug design, development and therapy · 2015Trial
- Buccal acetaminophen provides fast analgesia: two randomized clinical trials in healthy volunteers.Drug design, development and therapy · 2014Trial
- Acetaminophen inhibits diacylglycerol lipase synthesis of 2-arachidonoyl glycerol: Implications for nociception.Cell reports. Medicine · 2025Article
- The analgesic paracetamol metabolite AM404 acts peripherally to directly inhibit sodium channels.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The endocannabinoid anandamide mediates anti-inflammatory effects through activation of NR4A nuclear receptors.British journal of pharmacology · 2025Article
- Paracetamol and Caffeine Combination in Pain Management: A Narrative Review.Pain research & management · 2025Review
- Acetaminophen effects upon formalin-evoked flinching, postformalin, and postincisional allodynia and conditioned place preference.Pain reports · 2024Article
- Electroacupuncture Reduced Fibromyalgia-Pain-like Behavior through Inactivating Transient Receptor Potential V1 and Interleukin-17 in Intermittent Cold Stress Mice Model.Brain sciences · 2024Article
- Cannabinoid Analgesia in Postoperative Pain Management: From Molecular Mechanisms to Clinical Reality.International journal of molecular sciences · 2024Review
- Transcriptomic signature, bioactivity and safety of a non-hepatotoxic analgesic generating AM404 in the midbrain PAG region.Scientific reports · 2024Article
- Effect of the long-term use of a NOAEL dose of acetaminophen (paracetamol) on hepatic, renal, and neural tissues of aged albino rats.Open veterinary journal · 2024Article
- Imaging and Genetic Tools for the Investigation of the Endocannabinoid System in the CNS.International journal of molecular sciences · 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
- Analgesic Action of Acetaminophen via Kv7 Channels.International journal of molecular sciences · 2022Article
- Bioflavonoid exerts analgesic and anti-inflammatory effects via transient receptor potential 1 channel in a rat model.Arquivos de neuro-psiquiatria · 2022Article
- Paracetamol (Acetaminophen) and the Developing Brain.International journal of molecular sciences · 2021Review
- Long-term exposure to polypharmacy impairs cognitive functions in young adult female mice.Aging · 2021Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAcetaminophen, the major active metabolite of acetanilide in man, has become one of the most popular over-the-counter analgesic and antipyretic agents, consumed by millions of people daily. However, its mechanism of action is still a matter of debate. We have previously shown that acetaminophen is further metabolized to N-(4-hydroxyphenyl)-5Z,8Z,11Z,14Z -eicosatetraenamide (AM404) by fatty acid amide hydrolase (FAAH) in the rat and mouse brain and that this metabolite is a potent activator of transient receptor potential vanilloid 1 (TRPV(1)) in vitro. Pharmacological activation of TRPV(1) in the midbrain periaqueductal gray elicits antinociception in rats. It is therefore possible that activation of TRPV(1) in the brain contributes to the analgesic effect of acetaminophen. METHODOLOGY/PRINCIPAL
findingsHere we show that the antinociceptive effect of acetaminophen at an oral dose lacking hypolocomotor activity is absent in FAAH and TRPV(1) knockout mice in the formalin, tail immersion and von Frey tests. This dose of acetaminophen did not affect the global brain contents of prostaglandin E(2) (PGE(2)) and endocannabinoids. Intracerebroventricular injection of AM404 produced a TRPV(1)-mediated antinociceptive effect in the mouse formalin test. Pharmacological inhibition of TRPV(1) in the brain by intracerebroventricular capsazepine injection abolished the antinociceptive effect of oral acetaminophen in the same test.
conclusionsThis study shows that TRPV(1) in brain is involved in the antinociceptive action of acetaminophen and provides a strategy for developing central nervous system active oral analgesics based on the coexpression of FAAH and TRPV(1) in the brain.
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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.