ArticlePain research & management2023
Soluble Epoxide Hydrolase Inhibitor TPPU Alleviates Nab-Paclitaxel-Induced Peripheral Neuropathic Pain via Suppressing NF-
Article in Pain research & management, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 7 citations in OpenAlex.
- Inhibition of IL-17 Alleviates Blood-Brain Barrier Disruption Following Diffuse Axonal Injury Accompanied by Hyperglycemia Through the NF-κB Pathway.Mediators of inflammation · 2026Article
- Dimethoxybenzohomoadamantane-based soluble epoxide hydrolase inhibitors:Journal of enzyme inhibition and medicinal chemistry · 2025Article
- Inhibition of the Notch Pathway Alleviates Nab-Paclitaxel-Induced Peripheral Neuropathic Pain in Rats by Suppressing HMGB1/Caveolin-1 Signaling in the Spinal Cord.Mediators of inflammation · 2025Article
- Soluble epoxide hydrolase inhibition preserves alveolar bone in experimental periodontitis with estrogen deficiency.Frontiers in immunology · 2025Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
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Abstract
Objective: Paclitaxel-induced peripheral neuropathy (PIPN) is a debilitating and difficult-to-treat side effect of paclitaxel. Soluble epoxide hydrolase (sEH) can rapidly metabolize the endogenous anti-inflammatory mediators' epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids. This study aimed to assess whether the sEH inhibitor N-(1-(1-oxopropy)-4-piperidinyl]-N'-(trifluoromethoxy) phenyl)-urea (TPPU) plays a critical role in PIPN of rats and provides a new target for treatment. Methods: A Sprague-Dawley male rat model of PIPN induced by nab-paclitaxel was established. Rats were randomly divided into a control group, nab-paclitaxel group, and nab-paclitaxel + TPPU (sEH inhibitor) group, with 36 rats in each group. The effects of the sEH inhibitor TPPU on behavioural assays, apoptosis, glial activation, axonal injury, microstructure, and permeability of the blood-spinal cord barrier were detected, and the underlying mechanisms were explored by examining the expression of NF- Results: The results showed that the mechanical and thermal pain thresholds of rats were decreased after nab-paclitaxel treatment, accompanied by an increased expression of axonal injury-related proteins, enhanced cell apoptosis, aggravated destruction of vascular permeability, intense glial responses, and elevated inflammatory cytokines and oxidative stress in the L4-L6 spinal cord. TPPU restored the mechanical and thermal thresholds, decreased cell apoptosis, alleviated axonal injury and glial responses, and protected vascular permeability by increasing the expression of tight junction proteins. TPPU relieved PIPN by inhibiting the activation of the sEH and NF- Conclusion: These findings support a role for sEH in PIPN and suggest that the inhibition of sEH represents a potential new therapeutic target for PIPN.
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