Academic Journal
Activation of ASIC3 in nociceptors induces itch without overt pain in a novel mouse model of acid-evoked itch.
| Τίτλος: | Activation of ASIC3 in nociceptors induces itch without overt pain in a novel mouse model of acid-evoked itch. |
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| Συγγραφείς: | Shibata Y; Department of Anatomy and Neuroscience., Chaya R; Department of Nephro-urology., Yokoi Y; Endowed Department of Cognitive Function and Pathology, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, Nagoya., Kumamoto N; Department of Anatomy and Neuroscience., Ueda T; Department of Anatomy and Neuroscience., Yousif Elamin Yousif Z; Department of Anatomy and Neuroscience., Fujihara Y; Department of Experimental Genome Research, Research Institute for Microbial Diseases, The University of Osaka, Osaka, Japan., Ikawa M; Department of Experimental Genome Research, Research Institute for Microbial Diseases, The University of Osaka, Osaka, Japan., Yasui T; Department of Nephro-urology., Ugawa S; Department of Anatomy and Neuroscience. |
| Πηγή: | Neuroreport [Neuroreport] 2026 Oct 07; Vol. 37 (14), pp. 587-595. Date of Electronic Publication: 2026 Jul 30. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Lippincott Williams & Wilkins Country of Publication: England NLM ID: 9100935 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1473-558X (Electronic) Linking ISSN: 09594965 NLM ISO Abbreviation: Neuroreport Subsets: MEDLINE |
| Imprint Name(s): | Publication: London, England : Lippincott Williams & Wilkins Original Publication: Oxford, UK : Rapid Communications of Oxford Ltd., [1990- |
| Ιατρικοί όροι (MeSH): | Acid Sensing Ion Channels*/metabolism , Acid Sensing Ion Channels*/genetics , Pruritus*/metabolism , Pruritus*/chemically induced , Nociceptors*/metabolism, Ganglia, Spinal/metabolism ; Pain/metabolism ; Trigeminal Ganglion/metabolism ; Nerve Tissue Proteins/metabolism ; Animals ; Mice, Knockout ; Disease Models, Animal ; Mice ; Citric Acid ; Male ; Mice, Inbred C57BL ; Mice, Transgenic |
| Περίληψη: | Objective: Acid-sensing ion channel 3 (ASIC3), a proton-gated cation channel predominantly expressed in primary afferent nociceptors, is an acidosis-related pain generator. Previous experiments suggested that ASIC3 is also involved in the generation of itch. However, mechanistic links between ASIC3 and itch, including the expression of ASIC3 in itch-mediating primary sensory neurons, remain unclear. We examined ASIC3 expression in these sensory neurons and then investigated whether mild acid stimulation could induce ASIC3-dependent itch without overt pain in mice. Methods: Immunohistochemical analyses were performed using ASIC3-FLAG-enhanced green fluorescent protein-FLAG (FEF) expressing mice. Citric acid was applied with a brush to shaved skin of the nape of the neck or cheek in wild-type and ASIC3 knockout (ASIC3 -/- ) mice. Hindlimb scratching and, in the cheek model, forelimb facial wiping were recorded. Results: ASIC3-expressing neurons and plexin C1-positive/tachykinin 1-negative itch-mediating neurons essentially belonged to distinct subpopulations in dorsal root and trigeminal ganglia. Application of 0.2 M citric acid to the nape induced hindlimb scratching directed toward the citric acid-applied area in wild-type mice, and this response was significantly attenuated in ASIC3 -/- mice. Application of 0.5 M citric acid to the cheek induced ASIC3-dependent itch behavior (hindlimb scratching), accompanied by minimal or no pain behavior (forelimb wiping). Conclusion: Given the absence of ASIC3 in typical itch-mediating primary sensory neurons, citric acid-induced ASIC3 activation in nociceptive skin afferents primarily involved in pain likely underlies the observed itch behavior. As 0.5 M citric acid likely represents a weak noxious stimulus, weak activation of these pain-mediating afferents can evoke itch, supporting the intensity theory of itch. (Copyright © 2026 Wolters Kluwer Health, LLC. All rights reserved.) |
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| Contributed Indexing: | Keywords: acid-sensing ion channel 3; citric acid; immunohistochemistry; intensity theory of itch, knockin; knockout; plexin C1; scratching; tachykinin 1; wiping |
| Substance Nomenclature: | 0 (Acid Sensing Ion Channels) 0 (ASIC3 protein, mouse) 2968PHW8QP (Citric Acid) 0 (Nerve Tissue Proteins) |
| Entry Date(s): | Date Created: 20260814 Date Completed: 20260828 Latest Revision: 20260910 |
| Update Code: | 20260910 |
| DOI: | 10.1097/WNR.0000000000002296 |
| PMID: | 42596893 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1473-558X |
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| DOI: | 10.1097/WNR.0000000000002296 |