ArticleThe Journal of clinical investigation2008
Intracellular alkalization causes pain sensation through activation of TRPA1 in mice.
Article in The Journal of clinical investigation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
78 citing papers in PubMed, 1 synthesis or guideline pooled it, 134 citations in OpenAlex.
- Microbial volatile organic compounds and olfactory receptors in wound malodor.Frontiers in cellular and infection microbiology · 2026Pooled it
- Decay chemicals activate a pH-sensing pathway to initiate a persistent state.bioRxiv : the preprint server for biology · 2026Article
- Relationship between sensory irritation on skin surface and TRP channel activation.The journal of physiological sciences : JPS · 2026Article
- Article
- Evaluation of the Physicochemical and Biological Properties of Calcium-Silicate-Based Root-End Filling Materials.Journal of functional biomaterials · 2026Article
- The epidermal lipid-microbiome loop and immunity: Important players in atopic dermatitis.Journal of advanced research · 2025Review
- Trigeminal function in patients with COVID-associated olfactory loss.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2024Article
- Hot topic: Mapping of the human intranasal mucosal thermal sensitivity: A clinical study on thermal threshold and trigeminal receptors.PloS one · 2024Article
- The proton channel OTOP1 is a sensor for the taste of ammonium chloride.Nature communications · 2023Article
- Epigenetic Connections of the TRPA1 Ion Channel in Pain Transmission and Neurogenic Inflammation - a Therapeutic Perspective in Migraine?Molecular neurobiology · 2023Review
- Review
- Elucidation of the binding mode of organic polysulfides on the human TRPA1 receptor.Frontiers in physiology · 2023Article
- Review
- Inhibiting Hv1 channel in peripheral sensory neurons attenuates chronic inflammatory pain and opioid side effects.Cell research · 2022Article
- TRP Channels as Molecular Targets to Relieve Cancer Pain.Biomolecules · 2021Review
- Impact of the Protonation State of Phosphatidylinositol 4,5-Bisphosphate (PIP2) on the Binding Kinetics and Thermodynamics to Transient Receptor Potential Vanilloid (TRPV5): A Milestoning Study.The journal of physical chemistry. B · 2021Article
- Spontaneous, synchronous zinc spikes oscillate with neural excitability and calcium spikes in primary hippocampal neuron culture.Journal of neurochemistry · 2021Article
- Electrophile-Induced Conformational Switch of the Human TRPA1 Ion Channel Detected by Mass Spectrometry.International journal of molecular sciences · 2020Article
- Analysis of TRPA1 antagonist, A-967079, in plasma using high-performance liquid chromatography tandem mass-spectrometry.Journal of pharmaceutical analysis · 2020Article
- TRP Channels Role in Pain Associated With Neurodegenerative Diseases.Frontiers in neuroscience · 2020Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vertebrate cells require a very narrow pH range for survival. Cells accordingly possess sensory and defense mechanisms for situations where the pH deviates from the viable range. Although the monitoring of acidic pH by sensory neurons has been attributed to several ion channels, including transient receptor potential vanilloid 1 channel (TRPV1) and acid-sensing ion channels (ASICs), the mechanisms by which these cells detect alkaline pH are not well understood. Here, using Ca2+ imaging and patch-clamp recording, we showed that alkaline pH activated transient receptor potential cation channel, subfamily A, member 1 (TRPA1) and that activation of this ion channel was involved in nociception. In addition, intracellular alkalization activated TRPA1 at the whole-cell level, and single-channel openings were observed in the inside-out configuration, indicating that alkaline pH activated TRPA1 from the inside. Analyses of mutants suggested that the two N-terminal cysteine residues in TRPA1 were involved in activation by intracellular alkalization. Furthermore, intraplantar injection of ammonium chloride into the mouse hind paw caused pain-related behaviors that were not observed in TRPA1-deficient mice. These results suggest that alkaline pH causes pain sensation through activation of TRPA1 and may provide a molecular explanation for some of the human alkaline pH-related sensory disorders whose mechanisms are largely unknown.
Indexed as
Identifiers
What OpenQuestion holds
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.