Axonal transcriptome remodeling during PGE2 induced sensitization identifies Tnfrsf12a/FN14 as a regulator of sensory neuron excitability
Abstract
Axonal mRNA translation is a key regulator of neuronal plasticity, yet its contribution to inflammatory pain remains poorly defined. Here, we combine compartmentalized dorsal root ganglion (DRG) neuron cultures with RNA sequencing to map axonal and somatic transcriptomes and their remodeling following prostaglandin E2 (PGE2)-induced sensitization. We identify a conserved axonal transcriptome across embryonic and adult neurons, enriched for ribosomal and mitochondrial functions, supporting sustained local translation and metabolic activity. PGE2 triggers compartment-specific transcriptomic reprogramming, with axons showing enrichment of inflammatory and pain-related pathways, while somatic responses favor translational processes. Functionally, axonal PGE2 exposure enhances neuronal excitability and drives retrograde sensitization. Integrative analyses identify Tnfrsf12a (Fn14) as an axonally localized, PGE2-responsive transcript whose local knockdown reduces excitability and attenuates sensitization. These findings establish axonal transcriptome dynamics as key drivers of peripheral sensitization and highlight axonally localized mRNAs as spatially precise therapeutic targets for inflammatory pain.
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BibTeX
@article{arendttranholm2026axonal,
title = {{Axonal transcriptome remodeling during PGE2 induced sensitization identifies Tnfrsf12a/FN14 as a regulator of sensory neuron excitability}},
author = {Asta Arendt-Tranholm and Rafael Sebastián Fort and Rebecca Pope and Alex Rathbone and Paul Millns and Gareth Hathway and Jose Sotelo-Silveira and Victoria Chapman and Cornelia H. de Moor and Federico Dajas-Bailador},
journal = {iScience},
year = {2026},
month = oct,
doi = {10.1016/j.isci.2026.118049},
url = {https://www.cell.com/iscience/fulltext/S2589-0042(26)03432-2},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Axonal transcriptome remodeling during PGE2 induced sensitization identifies Tnfrsf12a/FN14 as a regulator of sensory neuron excitability
AU - Asta Arendt-Tranholm
AU - Rafael Sebastián Fort
AU - Rebecca Pope
AU - Alex Rathbone
AU - Paul Millns
AU - Gareth Hathway
AU - Jose Sotelo-Silveira
AU - Victoria Chapman
AU - Cornelia H. de Moor
AU - Federico Dajas-Bailador
PY - 2026
DA - 2026/10/29
JO - iScience
DO - 10.1016/j.isci.2026.118049
UR - https://www.cell.com/iscience/fulltext/S2589-0042(26)03432-2
AB - Axonal mRNA translation is a key regulator of neuronal plasticity, yet its contribution to inflammatory pain remains poorly defined. Here, we combine compartmentalized dorsal root ganglion (DRG) neuron cultures with RNA sequencing to map axonal and somatic transcriptomes and their remodeling following prostaglandin E2 (PGE2)-induced sensitization. We identify a conserved axonal transcriptome across embryonic and adult neurons, enriched for ribosomal and mitochondrial functions, supporting sustained local translation and metabolic activity. PGE2 triggers compartment-specific transcriptomic reprogramming, with axons showing enrichment of inflammatory and pain-related pathways, while somatic responses favor translational processes. Functionally, axonal PGE2 exposure enhances neuronal excitability and drives retrograde sensitization. Integrative analyses identify Tnfrsf12a (Fn14) as an axonally localized, PGE2-responsive transcript whose local knockdown reduces excitability and attenuates sensitization. These findings establish axonal transcriptome dynamics as key drivers of peripheral sensitization and highlight axonally localized mRNAs as spatially precise therapeutic targets for inflammatory pain.
SN - 2589-0042
ER -