ArticleCells2026
Integrative Proteomics Reveal Neuroimmune and Dopaminergic Alterations Across the Nociceptive Neuraxis in Neuropathic Pain.
Article in Cells, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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The trial behind it
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Who cites it
7 citing papers in PubMed.
- Semaphorins and Their Role in Neuropathic Pain.Life (Basel, Switzerland) · 2026Review
- Quercetin Alleviates Neuroinflammation in Chronic Insomnia by Modulating the RAGE/NF-κB Signaling Pathway: Insights from Network Pharmacology and In Vitro Validation.Biomedicines · 2026Article
- Temporal Transcriptomic Changes in the Cingulate Cortex of Neuropathic Pain Mice.Biomedicines · 2026Article
- CLARIX FLO Inhibits DRG Adhesion-Induced Neuropathic Pain Through the CD44-TRPV1 Signaling Pathway.International journal of molecular sciences · 2026Article
- Mrgprb4-Lineage Neurons Participate in the Intervention of TENS Effects on Chronic Pain and Anxiety-like Symptoms in an Inflammatory Pain Mouse Model.Biomedicines · 2026Article
- Early life social isolation stress and pain vulnerability: unraveling neuroimmune mechanisms and central sensitization.Frontiers in pharmacology · 2026Review
- Emerging roles of lipocalin-2-mediated neuroimmune interactions in chronic pain and itch.Frontiers in pharmacology · 2026Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Neuropathic pain (NP) arises from maladaptive changes in peripheral and central nociceptive circuits, yet molecular alterations spanning the entire pain neuraxis remain poorly understood. Neuroinflammation is increasingly recognized as a central mechanism in NP chronification, yet the region-specific molecular events linking immune activation to affective pain processing remain inadequately defined. In this study, we employed high-resolution LC-HRMS-based quantitative proteomics to investigate chronic constriction injury (CCI)-induced molecular alterations in the sciatic nerve (SN), spinal cord (SC), and orbitofrontal cortex (OFC) of male Wistar rats, a region critical for affective and cognitive pain modulation. Behavioral assessments confirmed the development of NP phenotypes and motor deficits. Proteomic profiling revealed exclusive and differentially expressed proteins enriched in neuroinflammatory pathways across all regions. S100 proteins (S100A8 and S100B) were significantly elevated in SN, SC, and OFC, as confirmed by immunofluorescence. Their up-regulation coincided with increased astrocyte (GFAP) and microglial (Iba-1) activation, highlighting a pervasive inflammatory milieu. Intriguingly, the OFC proteome demonstrated marked up-regulation of dopamine-regulating proteins and positive regulation of dopaminergic neurotransmission, suggesting involvement of reward-related analgesic circuits. Together, our findings delineate a "nociceptive neuraxis" driven by neuroimmune activation and neuromodulatory adaptations that interfaces with dopaminergic signaling to influence sensory and affective components of pain. This integrative molecular map highlights potential therapeutic targets, including glial-derived S100 proteins and dopamine modulators for the comprehensive management of NP.
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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 Socratic graph.