Evidence map›Paper›PMID 42317795›Full record

ArticleResearch (Washington, D.C.)2026

Multisite Chronic Pain Reveals Neuro-Immune-Metabolic Dysregulation across Rheumatoid Arthritis and Depression.

Qian Wang, Ye Ella Tian, Andrew Zalesky, Peng Wang, Zening Fu, Guozheng Feng, Dongmei Zhi, Ming Xu, Chunyang Wang, Xiaoli Wang and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Research (Washington, D.C.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Qian WangState Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China.
Ye Ella TianDepartment of Psychiatry, Melbourne Medical School, The University of Melbourne, Melbourne, Australia.
Andrew ZaleskyDepartment of Psychiatry, Melbourne Medical School, The University of Melbourne, Melbourne, Australia.
Peng WangState Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China.
Zening FuTri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, and Emory University, Atlanta, GA 30303, USA.
Guozheng FengTri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, and Emory University, Atlanta, GA 30303, USA.
Dongmei ZhiCenter for Addiction Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
Ming XuState Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China.
Chunyang WangState Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China.
Xiaoli WangSchool of Medical Imaging, Shandong Second Medical University, Weifang 261053, China.
Xizhen WangMedical Imaging Center Affiliated Hospital of Shandong Second Medical University, Weifang 261031, China.
Peiwu QinHengqin Lab, Zhuhai, Guangdong, China.
Vince D CalhounTri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, and Emory University, Atlanta, GA 30303, USA.
Rongtao JiangState Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China.
Jing SuiState Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China.ORCID https://orcid.org/0000-0001-6837-5966

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Multisite chronic pain (MCP) frequently co-occurs with immune and depressive disorders, yet whether it reflects coordinated cross-domain multi-omic dysregulation remains unknown. Using UK Biobank data (19,484 baseline participants; 32,870 to 399,476 for 15.9-year follow-up), we identified MCP-related multi-omic signatures spanning 59 biochemical measures, 168 metabolites, and 2,920 proteins. Notably, these signatures showed graded dysregulation [controls < depression < rheumatoid arthritis (RA) < comorbidity] with increasing disease burden, were associated with increased risk of incident RA and depression, and partially mediated their bidirectional association. We further identified HNMT as a depression risk factor, FGF21 as an RA risk factor, MME as a depression protective factor, and platelet count/FGF21/HNMT as shared factors using Mendelian randomization. Beyond disease outcomes, the signatures were associated with brain structural impairment and health-related behaviors (smoking/fish intake/physical activity), and aligned with polygenic liability for immune-metabolic-psychiatric traits. Together, these findings demonstrate that MCP reflects coordinated neuro-immune-metabolic dysregulation underlying RA-depression comorbidity and functions as a systems-level phenotype linking immune processes and depression.

Identifiers

PMID42317795
PMCPMC13272895

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.