ArticlePain2021
A peptide encoded within a 5' untranslated region promotes pain sensitization in mice.
Article in Pain, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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
12 citing papers in PubMed, 15 citations in OpenAlex.
- An upstream open reading frame represses translation of the neuronal potassium channel KCNQ2.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Genetic architecture of a Circadian Imbalance Index: genome-wide association, phenome-wide association, and Mendelian randomisation analyses.EBioMedicine · 2026Article
- Genome wide association study of a Circadian Imbalance Index in 312,935 European ancestry UK Biobank participants identifies loci related to diabetes, mood and myocardial infarction.Research square · 2025Article
- Article
- eEF2K regulates pain through translational control of BDNF.Molecular cell · 2025Article
- Small but mighty: the rise of microprotein biology in neuroscience.Frontiers in molecular neuroscience · 2024Article
- Inhibition of Nonsense-Mediated Decay Induces Nociceptive Sensitization through Activation of the Integrated Stress Response.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- A compendium of validated pain genes.WIREs mechanisms of disease · 2022Review
- Translation and natural selection of micropeptides from long non-canonical RNAs.Nature communications · 2022Article
- Global analyses of mRNA expression in human sensory neurons reveal eIF5A as a conserved target for inflammatory pain.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- A role for translational regulation by S6 kinase and a downstream target in inflammatory pain.British journal of pharmacology · 2021Article
- Ion Mobility Coupled to a Time-of-Flight Mass Analyzer Combined With Fragment Intensity Predictions Improves Identification of Classical Bioactive Peptides and Small Open Reading Frame-Encoded Peptides.Frontiers in cell and developmental biology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
abstractTranslational regulation permeates neuronal function. Nociceptors are sensory neurons responsible for the detection of harmful stimuli. Changes in their activity, termed plasticity, are intimately linked to the persistence of pain. Although inhibitors of protein synthesis robustly attenuate pain-associated behavior, the underlying targets that support plasticity are largely unknown. Here, we examine the contribution of protein synthesis in regions of RNA annotated as noncoding. Based on analyses of previously reported ribosome profiling data, we provide evidence for widespread translation in noncoding transcripts and regulatory regions of mRNAs. We identify an increase in ribosome occupancy in the 5' untranslated regions of the calcitonin gene-related peptide (CGRP/Calca). We validate the existence of an upstream open reading frame (uORF) using a series of reporter assays. Fusion of the uORF to a luciferase reporter revealed active translation in dorsal root ganglion neurons after nucleofection. Injection of the peptide corresponding to the calcitonin gene-related peptide-encoded uORF resulted in pain-associated behavioral responses in vivo and nociceptor sensitization in vitro. An inhibitor of heterotrimeric G protein signaling blocks both effects. Collectively, the data suggest pervasive translation in regions of the transcriptome annotated as noncoding in dorsal root ganglion neurons and identify a specific uORF-encoded peptide that promotes pain sensitization through GPCR signaling.
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.