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How people resolve pain: insights from human transcriptomics into immune activation and therapeutic innovations

2025· review· en· W4415161070 on OpenAlexaff
Andrey V. Bortsov, Sahel Jahangiri Esfahani, Lucas Vieira Lima, Ru‐Rong Ji, Jeffrey S. Mogil, Luda Diatchenko

Bibliographic record

VenuePain · 2025
Typereview
Languageen
FieldNeuroscience
TopicStress Responses and Cortisol
Canadian institutionsMcGill University
FundersNational Institutes of Health
KeywordsInflammationChronic painAcute painImmune systemTranscriptomeInflammatory response

Abstract

fetched live from OpenAlex

ABSTRACT: Patients with chronic pain commonly exhibit elevated inflammatory markers in the blood that correlate with reported pain and pain-related disability. Although inflammation is traditionally seen as a driver of chronic pain, recent transcriptomic data challenge this view, highlighting the beneficial role of acute inflammation in pain resolution. Here, we present evidence pointing to the overall dynamics of the inflammatory response being critical for pain resolution with the initial acute inflammatory response necessary to trigger pain resolution processes. We posit that chronic pain reflects an inability to resolve inflammation rather than its mere presence. Pharmacological or nonpharmacological reactivation of acute inflammatory pathways may thus provide novel therapeutic strategies targeting pain resolution instead of merely mitigating pain perception. This novel hypothesis regarding the effect of inflammation on pain is an example of what can be learned using unbiased approaches such as human transcriptomics. We believe that the near future will feature more examples of hypothesis generation using human genetics followed up by mechanistic experimentation in animal models.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.003
Threshold uncertainty score0.011

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0020.001
Science and technology studies0.0000.001
Scholarly communication0.0010.002
Open science0.0010.001
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0030.002

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.053
GPT teacher head0.311
Teacher spread0.258 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2025
Admission routes1
Has abstractyes

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