ArticleScientific reports2016
Hypoxia-induced sensitisation of TRPA1 in painful dysesthesia evoked by transient hindlimb ischemia/reperfusion in mice.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Induced Pluripotent Stem Cell-Based Platforms for Cardiac-Related Pain Research: Molecular Mechanisms, Experimental Models, and Therapeutic Applications.International journal of molecular sciences · 2026Review
- In Vivo Extracellular Recording Reveals Bidirectional Changes in Neuronal Activity in the Rat Spinal Dorsal Horn After Hindlimb Ischemia-Reperfusion.International journal of molecular sciences · 2026Article
- Role of TRP Channels in Cancer-Induced Bone Pain.International journal of molecular sciences · 2025Review
- Role of TRPA1 in Painful Cold Hypersensitivity.Advances in experimental medicine and biology · 2024Review
- Brg1 and RUNX1 synergy in regulating TRPM4 channel in mouse cardiomyocytes.Frontiers in pharmacology · 2024Article
- TRPA1 as a promising target in ischemia/reperfusion: A comprehensive review.Iranian journal of basic medical sciences · 2024Review
- Functions of TRPs in retinal tissue in physiological and pathological conditions.Frontiers in molecular neuroscience · 2024Review
- The astrocytic TRPA1 channel mediates an intrinsic protective response to vascular cognitive impairment via LIF production.Science advances · 2023Article
- TRPA1 as a OScientific reports · 2023Article
- Effect of Isokinetic Training with Blood Flow Restriction During Rest Interval Versus Exercise on Muscle Strength, Hypertrophy, and Perception: A Pilot Study.Juntendo Iji zasshi = Juntendo medical journal · 2023Article
- A Comparison of Pain Before and After Transfusion in Adult transfusion-dependent thalassemia (TDT) Using BPI-SF.F1000Research · 2023Observational
- Reactive Oxygen Species Cause Exercise-Induced Angina in a Myocardial Ischaemia-Reperfusion Injury Model.International journal of molecular sciences · 2022Article
- Article
- The effects of iloprost and beta3 receptor agonist on TRPA1 and TRPC1 immunreactivity in an experimental lower extremty ischemia-reperfusion injury model.Turkish journal of medical sciences · 2021Article
- Senso-Immunologic Prospects for Complex Regional Pain Syndrome Treatment.Frontiers in immunology · 2021Review
- MicroRNA-9 facilitates hypoxia-induced injury and apoptosis in H9c2 cells via targeting CDK8.Journal of biosciences · 2021Article
- TRPA1 gene variants hurting our feelings.Pflugers Archiv : European journal of physiology · 2020Review
- Non-Analgesic Symptomatic or Disease-Modifying Potential of TRPA1.Medical sciences (Basel, Switzerland) · 2019Review
- Emerging Perspectives on Pain Management by Modulation of TRP Channels and ANO1.International journal of molecular sciences · 2019Review
- Diabetes-induced microvascular complications at the level of the spinal cord: a contributing factor in diabetic neuropathic pain.The Journal of physiology · 2018Article
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Authors and funding
11 authors.
Funding
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Abstract
Dysesthesia is an unpleasant abnormal sensation, which is often accompanied by peripheral neuropathy or vascular impairment. Here, we examined the roles of transient receptor potential ankyrin 1 (TRPA1) in dysesthesia-like behaviours elicited by transient hindlimb ischemia (15-60 min) by tightly compressing the hindlimb, and reperfusion by releasing the ligature. The paw-withdrawal responses to tactile stimulation were reduced during ischemia and lasted for a while after reperfusion. Hindlimb ischemia/reperfusion elicited spontaneous licking of the ischemic hindpaw that peaked within 10 min. The licking was inhibited by reactive oxygen species (ROS) scavengers, a TRPA1 antagonist, or TRPA1 deficiency, but not by TRPV1 deficiency. In human TRPA1-expressing cells as well as cultured mouse dorsal root ganglion neurons, the H2O2-evoked TRPA1 response was significantly increased by pretreatment with hypoxia (80 mmHg) for 30 min. This hypoxia-induced TRPA1 sensitisation to H2O2 was inhibited by overexpressing a catalytically-inactive mutant of prolyl hydroxylase (PHD) 2 or in a TRPA1 proline mutant resistant to PHDs. Consistent with these results, a PHD inhibitor increased H2O2-evoked nocifensive behaviours through TRPA1 activation. Our results suggest that transient hindlimb ischemia/reperfusion-evoked spontaneous licking, i.e. painful dysesthesia, is caused by ROS-evoked activation of TRPA1 sensitised by hypoxia through inhibiting PHD-mediated hydroxylation of a proline residue in TRPA1.
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