ArticleThe journal of pain2023
Transforming Growth Factor-β-Activated Kinase 1 (TAK1) Mediates Chronic Pain and Cytokine Production in Mouse Models of Inflammatory, Neuropathic, and Primary Pain.
Article in The journal of pain, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 10 citations in OpenAlex.
- Mapping the ATP-Binding Pockets of FLT3 and TAK1: A Structural Basis for Dual Inhibition by FLT3-Targeted Therapies.ACS chemical biology · 2026Article
- A novel combination for in vivo breast cancer treatment: TAK1 inhibition combined with metformin and Lentinula edodes compounds synergistically reinvigorates CD8Journal of translational medicine · 2026Article
- [Puerarin alleviates rheumatoid arthritis in rats by modulating TAK1-mediated TLR4/NF-κB signaling pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Unraveling the Disease Mechanisms of Neuropathic Pain Through Constructing miRNA-mRNA Networks Based on a Rat Model.Brain and behavior · 2025Article
- Recent Issues in the Development and Application of Targeted Therapies with Respect to Individual Animal Variability.Animals : an open access journal from MDPI · 2025Review
- miR-374 family is a key regulator of chronic primary pain onset.Pain reports · 2024Article
- Emerging Molecular and Synaptic Targets for the Management of Chronic Pain Caused by Systemic Lupus Erythematosus.International journal of molecular sciences · 2024Review
- Effects of Branched-Chain Amino Acids on the Inflammatory Response Induced by LPS in Caco-2 Cells.Metabolites · 2024Article
- Transforming Growth Factor-β-Activated Kinase 1 (TAK1) Alleviates Inflammatory Joint Pain in Osteoarthritis and Gouty Arthritis Preclinical Models.Journal of pain research · 2024Article
- Delineation of the distinct inflammatory signaling roles of TAK1 and JAK1/3 in the CIA model of rheumatoid arthritis.Pharmacology research & perspectives · 2023Article
- The effects of Phycocyanobilin on experimental arthritis involve the reduction in nociception and synovial neutrophil infiltration, inhibition of cytokine production, and modulation of the neuronal proteome.Frontiers in immunology · 2023Article
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Corrections and comments
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
Abstract
The origin of chronic pain is linked to inflammation, characterized by increased levels of proinflammatory cytokines in local tissues and systemic circulation. Transforming growth factor beta-activated kinase 1 (TAK1) is a key regulator of proinflammatory cytokine signaling that has been well characterized in the context of cancer and autoimmune disorders, yet its role in chronic pain is less clear. Here, we evaluated the ability of our TAK1 small-molecule inhibitor, takinib, to attenuate pain and inflammation in preclinical models of inflammatory, neuropathic, and primary pain. Inflammatory, neuropathic, and primary pain was modeled using intraplantar complete Freund's adjuvant (CFA), chronic constriction injury (CCI), and systemic delivery of the catechol-O-methyltransferase (COMT) inhibitor OR486, respectively. Behavioral responses evoked by mechanical and thermal stimuli were evaluated in separate groups of mice receiving takinib or vehicle prior to pain induction (baseline) and over 12 days following CFA injection, 4 weeks following CCI surgery, and 6 hours following OR486 delivery. Hindpaw edema was also measured prior to and 3 days following CFA injection. Upon termination of behavioral experiments, dorsal root ganglia (DRG) were collected to measure cytokines. We also evaluated the ability of takinib to modulate nociceptor activity via in vitro calcium imaging of neurons isolated from the DRG of Gcamp3 mice. In all 3 models, TAK1 inhibition significantly reduced hypersensitivity to mechanical and thermal stimuli and expression of proinflammatory cytokines in DRG. Furthermore, TAK1 inhibition significantly reduced the activity of tumor necrosis factor (TNF)-primed/capsaicin-evoked DRG nociceptive neurons. Overall, our results support the therapeutic potential of TAK1 as a novel drug target for the treatment of chronic pain syndromes with different etiologies. PERSPECTIVE: This article reports the therapeutic potential of TAK1 inhibitors for the treatment of chronic pain. This new treatment has the potential to provide a greater therapeutic offering to physicians and patients suffering from chronic pain as well as reduce the dependency on opioid-based pain treatments.
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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 OpenQuestion graph.