Soluble epoxide hydrolase inhibition is antinociceptive in a mouse model of diabetic neuropathy

Karen Wagner, Jun Yang, Bora Inceoglu, Bruce D. Hammock

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Neuropathic pain is currently an insufficiently treated clinical condition. There remains a critical need for efficacious therapies without severe side effects to treat the uniquely persistent and tonic pain of neuropathy. Inhibitors of the soluble epoxide hydrolase (sEH) enzyme that stabilize endogenous epoxy fatty acids have demonstrated antihyperalgesia in clinical chronic inflammatory pain and modeled neuropathic pain. Recently, the conditioned place preference assay has been used to evaluate the tonic nature of neuropathy in several animal models. The current experiments use the conditioned place preference assay alongside withdrawal thresholds to investigate the antihyperalgesic efficacy of sEH inhibitors in a murine model of diabetic neuropathy. Here, the sEH inhibitor trans-4-[4-(3- trifluoromethoxyphenyl-1-ureido)-cyclohexyloxy]-benzoic acid (t-TUCB) at 10 mg/kg induced a robust place preference in diabetic neuropathic mice representative of pain relief. Importantly, this effect was absent both in control mice and in sEH-knockout mice at the same dose, indicating that t-TUCB is not positively reinforcing or rewarding. When compared to gabapentin, t-TUCB elicited a similar degree of withdrawal threshold improvement without the same degree of spontaneous locomotion decline in neuropathic mice. Overall, these experiments show that inhibiting the sEH enzyme attenuates chronic pain and offers an alternative to current side-effect-limited therapies to meet this clinical need. Perspective These experiments demonstrate antihyperalgesia in a murine chronic pain model mediated by inhibiting the sEH enzyme. The results of this study indicate that inhibiting the sEH is a promising alternative for blocking chronic pain.

Original languageEnglish (US)
Pages (from-to)907-914
Number of pages8
JournalJournal of Pain
Issue number9
StatePublished - 2014


  • antihyperalgesia
  • conditioned place preference
  • epoxy fatty acids
  • Neuropathic pain
  • soluble epoxide hydrolase

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Neurology
  • Clinical Neurology


Dive into the research topics of 'Soluble epoxide hydrolase inhibition is antinociceptive in a mouse model of diabetic neuropathy'. Together they form a unique fingerprint.

Cite this