ArticleCellular and molecular neurobiology2022
TRAF6 Contributes to CFA-Induced Spinal Microglial Activation and Chronic Inflammatory Pain in Mice.
Article in Cellular and molecular neurobiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Aberrant CX3CL1-CX3CR1 Signaling Reprograms Microglial Exosome Secretion via KIFC2 to Drive Cognitive Impairment in Chronic Pain.International journal of molecular sciences · 2026Article
- Docosahexaenoic Acid Attenuates Visceral Pain by Suppressing Spinal CXCL10/CXCR3/ERK Signaling.Nutrients · 2026Article
- Mechanical cues as immunomodulators in neuroinflammation-driven spinal sensitization: analgesic mechanisms and therapeutic strategies.Frontiers in immunology · 2026Review
- Role of ncRNAs in the Development of Chronic Pain.Non-coding RNA · 2025Review
- Dexmedetomidine suppresses microglial activation in postoperative cognitive dysfunction via the mmu-miRNA-125/TRAF6 signaling axis.Open medicine (Warsaw, Poland) · 2025Article
- Embryonic Lethal Abnormal Visual-Like Protein 1 Aggravates Caerulein-Induced AR42J Cell Injury and Macrophage M1 Polarization to Accelerate Acute Pancreatitis by Upregulating TRAF6.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2025Article
- Trifluoro-Icaritin Ameliorates Neuroinflammation Against Complete Freund's Adjuvant-Induced Microglial Activation by Improving CB2 Receptor-Mediated IL-10/β-endorphin Signaling in the Spinal Cord of Rats.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Article
- TRAF6 promotes spinal microglial M1 polarization to aggravate neuropathic pain by activating the c-JUN/NF-kB signaling pathway.Cell biology and toxicology · 2024Article
- Andrographolide inhibits the activation of spinal microglia and ameliorates mechanical allodynia.Metabolic brain disease · 2024Article
- Structural Characterization of TRAF6 N-Terminal for Therapeutic Uses and Computational Studies on New Derivatives.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Antioxidant Cascade Nanoenzyme Antagonize Inflammatory Pain by Modulating MAPK/p-65 Signaling Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Astrocytes in Chronic Pain: Cellular and Molecular Mechanisms.Neuroscience bulletin · 2023Review
- A-80426 suppresses CFA-induced inflammatory pain by suppressing TRPV1 activity via NFκB and PI3K pathways in mice.Clinics (Sao Paulo, Brazil) · 2023Article
- Microglia activation in central nervous system disorders: A review of recent mechanistic investigations and development efforts.Frontiers in neurology · 2023Review
- A Metabolomic Study of the Analgesic Effect of Lappaconitine Hydrobromide (LAH) on Inflammatory Pain.Metabolites · 2022Article
- Modulation of KIF17/NR2B crosstalk by tozasertib attenuates inflammatory pain in rats.Inflammopharmacology · 2022Article
- Caloric Restriction Alleviates CFA-Induced Inflammatory PainFrontiers in neuroscience · 2022Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Tumor necrosis factor receptor-associated factor 6 (TRAF6) has been reported to be expressed in spinal astrocytes and is involved in neuropathic pain. In this study, we investigated the role and mechanism of TRAF6 in complete Freund's adjuvant (CFA)-evoked chronic inflammatory hypersensitivity and the effect of docosahexaenoic acid (DHA) on TRAF6 expression and inflammatory pain. We found that TRAF6 was dominantly increased in microglia at the spinal level after intraplantar injection of CFA. Intrathecal TRAF6 siRNA alleviated CFA-triggered allodynia and reversed the upregulation of IBA-1 (microglia marker). In addition, intrathecal administration of DHA inhibited CFA-induced upregulation of TRAF6 and IBA-1 in the spinal cord and attenuated CFA-evoked mechanical allodynia. Furthermore, DHA prevented lipopolysaccharide (LPS)-caused increase of TRAF6 and IBA-1 in both BV2 cell line and primary cultured microglia. Finally, intrathecal DHA reduced LPS-induced upregulation of spinal TRAF6 and IBA-1, and alleviated LPS-induced mechanical allodynia. Our findings indicate that TRAF6 contributes to pain hypersensitivity via regulating microglial activation in the spinal dorsal horn. Direct inhibition of TRAF6 by siRNA or indirect inhibition by DHA may have therapeutic effects on chronic inflammatory pain.
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