ArticleThe Journal of biological chemistry2010
The general anesthetic propofol excites nociceptors by activating TRPV1 and TRPA1 rather than GABAA receptors.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 115 citations in OpenAlex.
- Optimal dosing of ciprofol for gastrointestinal endoscopy: a systematic review and network meta-analysis.BMC gastroenterology · 2025Pooled it
- Skin cooling and topical application of menthol can reduce propofol injection-induced pain, a randomized trial.Medicine · 2025Trial
- The efficacy and safety of ciprofol versus propofol in patients undergoing painless hysteroscopy: a randomized, double-blind, controlled trial.BMC anesthesiology · 2024Trial
- Efficacy of 6% Hydroxyethyl Starch and 2% Lidocaine in Reducing the Pain of Propofol Injection: A randomised, placebo-controlled trial.Sultan Qaboos University medical journal · 2024Trial
- Structural dynamics and permeability of the TRPV3 pentamer.Nature communications · 2025Article
- Review
- Anesthetic- and Analgesic-Related Drugs Modulating Both Voltage-Gated NaBiomolecules · 2024Review
- Propofol-Induced Fasciculations in a Patient With Obstructive Sleep Apnea: A Case Report.Cureus · 2024Article
- The Interaction Mechanism Between C14-Polyacetylene Compounds and the Rat TRPA1 Receptor: An In Silico Study.International journal of molecular sciences · 2024Article
- Nociceptive transient receptor potential ankyrin 1 (TRPA1) in sensory neurons are targets of the antifungal drug econazole.BMC pharmacology & toxicology · 2024Article
- Depolarization of mouse DRG neurons by GABA does not translate into acute pain or hyperalgesia in healthy human volunteers.PloS one · 2024Article
- Evaluation of Peripheral Versus Central Route of Ondansetron as Pretreatment to Prevent Pain on the Injection of Propofol: A Randomized Controlled Study.Turkish journal of anaesthesiology and reanimation · 2023Article
- Modification of the TRP Channel TRPA1 as a Relevant Factor in Migraine-Related Intracranial Hypersensitivity.International journal of molecular sciences · 2023Review
- Features and mechanisms of propofol-induced protein kinase C (PKC) translocation and activation in living cells.Frontiers in pharmacology · 2023Article
- TRPA1-dependent and -independent activation by commonly used preservatives.Frontiers in pharmacology · 2023Article
- TRPA1 Polymorphisms Modify the Hypotensive Responses to Propofol with No Change in Nitrite or Nitrate Levels.Current issues in molecular biology · 2022Article
- Article
- Rhythmic Change of Cortical Hemodynamic Signals Associated with Ongoing Nociception in Awake and Anesthetized Individuals: An Exploratory Functional Near Infrared Spectroscopy Study.Anesthesiology · 2021Article
- The Agonist Action of Alkylphenols on TRPA1 Relates to Their Effects on Membrane Lipid Order: Implications for TRPA1-Mediated Chemosensation.International journal of molecular sciences · 2021Article
- The Role of TRPA1 in Skin Physiology and Pathology.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Anesthetic agents can induce a paradox activation and sensitization of nociceptive sensory neurons and, thus, potentially facilitate pain processing. Here we identify distinct molecular mechanisms that mediate an activation of sensory neurons by 2,6-diisopropylphenol (propofol), a commonly used intravenous anesthetic known to elicit intense pain upon injection. Clinically relevant concentrations of propofol activated the recombinant transient receptor potential (TRP) receptors TRPA1 and TRPV1 heterologously expressed in HEK293t cells. In dorsal root ganglion (DRG) neurons, propofol-induced activation correlated better to expression of TRPA1 than of TRPV1. However, pretreatment with the protein kinase C activator 4β-phorbol 12-myristate 13-acetate (PMA) resulted in a significantly sensitized propofol-induced activation of TRPV1 in DRG neurons as well as in HEK293t cells. Pharmacological and genetic silencing of both TRPA1 and TRPV1 only partially abrogated propofol-induced responses in DRG neurons. The remaining propofol-induced activation was abolished by the selective γ-aminobutyric acid, type A (GABA(A)) receptor antagonist picrotoxin. Propofol but not GABA evokes a release of calcitonin gene-related peptide, a key component of neurogenic inflammation, from isolated peripheral nerves of wild-type but not TRPV1 and TRPA1-deficient mice. Moreover, propofol but not GABA induced an intense pain upon intracutaneous injection. As both the release of calcitonin gene-related peptide and injection pain by propofol seem to be independent of GABA(A) receptors, our data identify TRPV1 and TRPA1 as key molecules for propofol-induced excitation of sensory neurons. This study warrants further investigations into the role of anesthetics to induce nociceptor sensitization and to foster postoperative 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.