Evidence map›Paper›PMID 40946312›Full record

ArticleCell reports2025

Metabolic reprogramming in the spinal cord drives the transition to pain chronicity.

Alex Mabou Tagne, Yannick Fotio, Hye-Lim Lee, Kwang-Mook Jung, Jean Katz, Faizy Ahmed, Johnny Le, Richard Bazinet, Cholsoon Jang, Daniele Piomelli

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Pharmacokinetic and pharmacodynamic properties of cannabigerol in male mice.The Journal of pharmacology and experimental therapeutics · 2026
    Article
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Alex Mabou TagneDepartment of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA, USA.
Yannick FotioDepartment of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA, USA.
Hye-Lim LeeDepartment of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA, USA.
Kwang-Mook JungDepartment of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA, USA.
Jean KatzDepartment of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA, USA.
Faizy AhmedDepartment of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA, USA.
Johnny LeDepartment of Biological Chemistry, University of California, Irvine, Irvine, CA, USA.
Richard BazinetDepartment of Nutritional Sciences, University of Toronto, Toronto, ON, Canada.
Cholsoon JangDepartment of Biological Chemistry, University of California, Irvine, Irvine, CA, USA.
Daniele PiomelliDepartment of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA, USA; Department of Biological Chemistry, University of California, Irvine, Irvine, CA, USA; Department of Pharmaceutical Sciences, University of California, Irvine, Irvine, CA, USA. Electronic address: piomelli@hs.uci.edu.

Funding

The lipid hydrolase NAAA as a target for non-addictive analgesic medicationsR01DA055578 · NIDA · UNIVERSITY OF CALIFORNIA-IRVINE · PI Daniele Piomelli · 2023 to 2026
$2.3M
Elucidating dietary fructose and alcohol interactions during liver cancer developmentR01AA029124 · NIAAA · UNIVERSITY OF CALIFORNIA-IRVINE · PI JANG, CHOLSOON · 2021 to 2025
$2.0M
Elucidating alcohol-induced metabolic remodeling of critical organsR21AA030358 · NIAAA · UNIVERSITY OF CALIFORNIA-IRVINE · PI JANG, CHOLSOON, SELDIN, MARCUS MICHAEL · 2023 to 2023
$412k
A role for peripheral NAAA-regulated lipid signaling in the control of hyperalgesic primingK99AT012658 · NCCIH · UNIVERSITY OF CALIFORNIA-IRVINE · PI FOTIO, YANNICK · 2023 to 2023
$238k
Elucidating the role of nonessential amino acid metabolism in diabetic skin woundsF31DK134173 · NIDDK · UNIVERSITY OF CALIFORNIA-IRVINE · PI Johnny Le · 2023 to 2026
$197k
NCCIH NIH HHS K99 AT012658NIAAA NIH HHS R01 AA029124NIAAA NIH HHS R21 AA030358NIDA NIH HHS R01 DA055578NIDDK NIH HHS F31 DK134173
6 · The paper itself

Abstract

Acute injuries can progress into painful states that endure long after healing. The mechanisms underlying this transition remain unclear, but metabolic adaptations to the bioenergy demands imposed by injury are plausible contributors. Here we show that peripheral injury activates AKT/mTORC1 in afferent segments of the mouse spinal cord, redirecting local core metabolism toward biomass production while simultaneously suppressing autophagy-mediated biomass reclamation. This metabolic shift supports neuroplasticity but creates a resource bottleneck that depletes critical spinal cord nutrients. Preventing this depletion with a modified diet normalizes biomass generation and autophagy and halts the transition to chronic pain. This effect, observed across multiple pain models, requires activation of the nutrient sensors, sirtuin-1 and AMPK, as well as restoration of autophagy. The findings identify metabolic reprogramming and consequent autophagy suppression as key drivers of the progression to pain chronicity and highlight nutritional and pharmacological interventions that could prevent this progression after surgery or other physical traumas.

Indexed as

Chronic PainSpinal CordAnimalsAutophagyMaleMechanistic Target of Rapamycin Complex 1Metabolic ReprogrammingMiceMice, Inbred C57BLProto-Oncogene Proteins c-aktSirtuin 1Mechanistic Target of Rapamycin Complex 1Proto-Oncogene Proteins c-aktSirtuin 1AMPKautophagychronic painCP: MetabolismCP: NeurosciencemTORC1nutritionsirtuin-1

Identifiers

PMID40946312
PMCPMC12717780

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.