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Papers of the Week


Papers: 30 Nov 2019 - 6 Dec 2019


Animal Studies, Pharmacology/Drug Development


2020 Feb 01


Brain Res


1728

Soluble epoxide hydrolase inhibitor mediated analgesia lacks tolerance in rat models.

Authors

Wagner KM, Atone J, Hammock BD
Brain Res. 2020 Feb 01; 1728:146573.
PMID: 31790682.

Abstract

Effectively treating chronic pain remains a therapeutic challenge in the clinic. Recent evidence has shown the inhibition of the soluble epoxide hydrolase (sEH) to be an effective strategy to limit chronic pain in preclinical models, horses and companion animals. Determining the safety ofsEH inhibition in addition to this demonstrated efficacy is a critical step to the further development ofsEH inhibitors (sEHI) as analgesics. Here we describe a comparison of thesEHI TPPU with other first in class analgesics for human chronic pain. We assess the development of tolerance to the analgesia mediated by TPPU with extended use. We also assess for CNS effects by measuring changes in motor control and functioning. ThesEHI are multimodal analgesics that have demonstrated potent efficacy against chronic pain. They have previously been tested and show no reward potential using operant methods. The results of the current experiments show that they lack motor function effects and also lack the development of tolerance with extended dosing.