ArticleJournal of translational medicine2023
The soluble epoxide hydrolase inhibitor TPPU improves comorbidity of chronic pain and depression via the AHR and TSPO signaling.
Article in Journal of translational medicine, 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, 30 citations in OpenAlex.
- TPPU protects against seizures and seizure-associated comorbidities by inhibiting the Akt/mTOR signaling pathway in KA-induced convulsant mice.Frontiers in immunology · 2026Article
- Shen-Ling-Bai-Zhu-San Mitigates Ulcerative Colitis by Enhancing Intestinal Barrier Integrity via the AhR-CYP1A1-NF-κB Signal Pathway.Combinatorial chemistry & high throughput screening · 2026Article
- The aryl hydrocarbon receptor and kynurenine pathway: connecting inflammatory bowel disease and depression via the microbiota gut brain axis.Frontiers in neuroscience · 2026Review
- Exploring Mechanisms of Ephx2 in Treating Atherosclerosis Using Independent Cascade Model and Adverse Outcome Pathways.Combinatorial chemistry & high throughput screening · 2026Article
- The role of arachidonic acid metabolites in major depressive disorder: mechanisms and therapeutic implications.Metabolic brain disease · 2025Review
- Epoxide Hydrolase Inhibitors for the Treatment of Alzheimer's Disease and Other Neurological Disorders: A Comprehensive Review.Biomedicines · 2025Review
- Effects of soluble epoxide hydrolase inhibition on liver injury and gut microbiota in mice chronically fed ethanol.Alcohol, clinical & experimental research · 2025Article
- Chronic Pain and Comorbid Emotional Disorders: Neural Circuitry and Neuroimmunity Pathways.International journal of molecular sciences · 2025Review
- Corticospinal Excitability in Bilateral M1 Hand Areas: Association with Neuropathic Pain After Spinal Cord Injury.Journal of pain research · 2025Article
- HCN channels in the lateral habenula regulate pain and comorbid depressive-like behaviors in mice.CNS neuroscience & therapeutics · 2024Article
- Inhibition of soluble epoxide hydrolase enhances the dentin-pulp complex regeneration mediated by crosstalk between vascular endothelial cells and dental pulp stem cells.Journal of translational medicine · 2024Article
- Role of soluble epoxide hydrolase in the abnormal activation of fibroblast-like synoviocytes from patients with rheumatoid arthritis.Clinical immunology (Orlando, Fla.) · 2023Article
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundPatients suffering from chronic pain often also exhibit depression symptoms. Soluble epoxide hydrolase (sEH) inhibitors can decrease blood levels of inflammatory cytokines. However, whether inhibiting sEH signaling is beneficial for the comorbidity of pain and depression is unknown.
methodsAccording to a sucrose preference test (SPT), spared nerve injury (SNI) mice were classified into pain with or without an anhedonia phenotype. Then, sEH protein expression and inflammatory cytokines were assessed in selected tissues. Furthermore, we used sEH inhibitor TPPU to determine the role of sEH in chronic pain and depression. Importantly, agonists and antagonists of aryl hydrocarbon receptor (AHR) and translocator protein (TSPO) were used to explore the pathogenesis of sEH signaling.
resultsIn anhedonia-susceptible mice, the tissue levels of sEH were significantly increased in the medial prefrontal cortex (mPFC), hippocampus, spinal cord, liver, kidney, and gut. Importantly, serum CYP1A1 and inflammatory cytokines, such as interleukin 1β (IL-1β) and the tumor necrosis factor α (TNF-α), were increased simultaneously. TPPU improved the scores of mechanical withdrawal threshold (MWT) and SPT, and decreased the levels of serum CYP1A1 and inflammatory cytokines. AHR antagonist relieved the anhedonia behaviors but not the algesia behaviors in anhedonia-susceptible mice, whereas an AHR agonist abolished the antidepressant-like effect of TPPU. In addition, a TSPO agonist exerted a similar therapeutic effect to that of TPPU, whereas pretreatment with a TSPO antagonist abolished the antidepressant-like and analgesic effects of TPPU.
conclusionssEH underlies the mechanisms of the comorbidity of chronic pain and depression and that TPPU exerts a beneficial effect on anhedonia behaviors in a pain model via AHR and TSPO signaling.
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