ArticleScience translational medicine2014
Aldehyde dehydrogenase-2 regulates nociception in rodent models of acute inflammatory pain.
Article in Science translational medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04732000 (Oxidative Stress and Surgical Recovery), which is not on this map. Cited by 76 papers.
What it found
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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.
Oxidative Stress and Surgical Recovery
Who cites it
76 citing papers in PubMed, 103 citations in OpenAlex.
- Reactive aldehyde species-mediated neuropathic pain in spinal cord injury: Mechanisms and therapeutic opportunities.Neural regeneration research · 2026Article
- Mitochondrial vulnerability to aldehydic load and the role mitochondrial aldehyde dehydrogenases.Pharmacological research · 2026Review
- Common human ALDH1B1 and ALDH2 variants increase neuroinflammatory response to a single ethanol dose in mice.Science advances · 2026Article
- Reactive carbonyl species in health and chronic disease: from methylglyoxal to an integrative network of metabolic regulation.Cardiovascular diabetology · 2026Review
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- The Pathological Role and Therapeutic potential of ALDH2 in acrolein detoxification Following Spinal Cord Injury in Mice.bioRxiv : the preprint server for biology · 2025Article
- The association between solid fuel use for heating and cooking and low back pain and neck pain in middle-aged to elderly Chinese adults: a cross-sectional and panel data analysis.BMC public health · 2025Article
- Aldehyde Dehydrogenase 2 Gene Mutation May Reduce the Risk of Rupture of Intracranial Aneurysm in Chinese Han Population.Journal of stroke · 2025Article
- ALDH2 dysfunction and alcohol cooperate in cancer stem cell enrichment.Carcinogenesis · 2024Article
- A common East-Asian ALDH2 mutation causes metabolic disorders and the therapeutic effect of ALDH2 activators.Nature communications · 2023Article
- The role of aldehyde dehydrogenase 2 in cardiovascular disease.Nature reviews. Cardiology · 2023Review
- A Common East Asian aldehyde dehydrogenase 2*2 variant promotes ventricular arrhythmia with chronic light-to-moderate alcohol use in mice.Communications biology · 2023Article
- Gene Therapy to Treat Osteopenia Associated With Chronic Ethanol Consumption and Aldehyde Dehydrogenase 2 Deficiency.JBMR plus · 2023Article
- A human TRPV1 genetic variant within the channel gating domain regulates pain sensitivity in rodents.The Journal of clinical investigation · 2023Article
- Effects of intracardiac delivery of aldehyde dehydrogenase 2 gene in myocardial salvage.Gene therapy · 2023Article
- Chronic pain in Alzheimer's disease: Endocannabinoid system.Experimental neurology · 2023Review
- SGLT2 inhibitor ameliorates endothelial dysfunction associated with the commonScience translational medicine · 2023Article
- Implication of the cooking oil-peroxidation product "hydroxynonenal" for Alzheimer's disease.Frontiers in aging neuroscience · 2023Review
- Aldehyde Dehydrogenase 2 Activator Augments the Beneficial Effects of Empagliflozin in Mice with Diabetes-Associated HFpEF.International journal of molecular sciences · 2022Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Exogenous aldehydes can cause pain in animal models, suggesting that aldehyde dehydrogenase-2 (ALDH2), which metabolizes many aldehydes, may regulate nociception. To test this hypothesis, we generated a knock-in mouse with an inactivating point mutation in ALDH2 (ALDH2*2), which is also present in human ALDH2 of ~540 million East Asians. The ALDH2*1/*2 heterozygotic mice exhibited a larger response to painful stimuli than their wild-type littermates, and this heightened nociception was inhibited by an ALDH2-selective activator (Alda-1). No effect on inflammation per se was observed. Using a rat model, we then showed that nociception tightly correlated with ALDH activity (R(2) = 0.90) and that reduced nociception was associated with less early growth response protein 1 (EGR1) in the spinal cord and less reactive aldehyde accumulation at the insult site (including acetaldehyde and 4-hydroxynonenal). Further, acetaldehyde- and formalin-induced nociceptive behavior was greater in the ALDH2*1/*2 mice than in the wild-type mice. Finally, Alda-1 treatment was even beneficial when given after the inflammatory agent was administered. Our data in rodent models suggest that the mitochondrial enzyme ALDH2 regulates nociception and could serve as a molecular target for pain control, with ALDH2 activators, such as Alda-1, as potential non-narcotic, cardiac-safe analgesics. Furthermore, our results suggest a possible genetic basis for East Asians' apparent lower pain tolerance.
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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.