ArticleScience advances2021
NAAA-regulated lipid signaling governs the transition from acute to chronic pain.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Peripheral nerve injury induces an immunometabolic signature involving reduced free fatty-acid pools.Metabolic brain disease · 2026Article
- Hyperuricemia aggravates acute pancreatitis through CNR1-mediated inflammatory signaling and gut-pancreas axis dysregulation: a multi-omics and clinical study.Scientific reports · 2026Article
- Analgesia through FKBP51 inhibition at disease onset confers lasting relief from sensory and emotional chronic pain symptoms.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Metabolic reprogramming in the spinal cord drives the transition to pain chronicity.Cell reports · 2025Article
- Astrocyte inhibition and PV interneuron activation: key mechanisms in electroacupuncture's effect on pain-anxiety comorbidity.Chinese medicine · 2025Article
- Novel findings regarding the role of the endocannabinoid system in pediatric functional gastrointestinal disorders.Pain reports · 2025Article
- Fatty acid amide hydrolase inhibition alleviates anxiety-like symptoms in a rat model used to study post-traumatic stress disorder.Psychopharmacology · 2025Article
- Neuroprotective, anti-inflammatory, and analgesic activity of palmitoylethanolamide in sickle cell mice.Blood advances · 2025Article
- Metabolic reprogramming in the spinal cord drives the transition to pain chronicity.bioRxiv : the preprint server for biology · 2025Article
- Targeting microglial NAAA-regulated PEA signaling counters inflammatory damage and symptom progression of post-stroke anxiety.Cell communication and signaling : CCS · 2025Article
- Enhancement of peripheral fatty acyl ethanolamide signaling prevents stress-induced social avoidance and anxiety-like behaviors in male rats.Psychopharmacology · 2025Article
- Review
- N-acylethanolamine acid amidase inhibitor-loaded polymeric micelles in the treatment of dry eye disease.International journal of ophthalmology · 2025Article
- ΔThe Journal of pharmacology and experimental therapeutics · 2024Article
- NAAA-regulated lipid signaling in monocytes controls the induction of hyperalgesic priming in mice.Nature communications · 2024Article
- Goods and Bads of the Endocannabinoid System as a Therapeutic Target: Lessons Learned after 30 Years.Pharmacological reviews · 2023Review
- Association between single nucleotide variants and severe chronic pain in older adult patients after lower extremity arthroplasty.Journal of orthopaedic surgery and research · 2023Article
- Targeting NAAA counters dopamine neuron loss and symptom progression in mouse models of parkinsonism.Pharmacological research · 2022Article
- α-Acylamino-β-lactoneAntioxidants (Basel, Switzerland) · 2022Article
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
Chronic pain affects 1.5 billion people worldwide but remains woefully undertreated. Understanding the molecular events leading to its emergence is necessary to discover disease-modifying therapies. Here we show that N-acylethanolamine acid amidase (NAAA) is a critical control point in the progression to pain chronicity, which can be effectively targeted by small-molecule therapeutics that inhibit this enzyme. NAAA catalyzes the deactivating hydrolysis of palmitoylethanolamide, a lipid-derived agonist of the transcriptional regulator of cellular metabolism, peroxisome proliferator-activated receptor-α (PPAR-α). Our results show that disabling NAAA in spinal cord during a 72-h time window following peripheral tissue injury halts chronic pain development in male and female mice by triggering a PPAR-α-dependent reprogramming of local core metabolism from aerobic glycolysis, which is transiently enhanced after end-organ damage, to mitochondrial respiration. The results identify NAAA as a crucial control node in the transition to chronic pain and a molecular target for disease-modifying medicines.
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.