Analgesic effects of soluble epoxide hydrolase inhibitor in K/BxN serum transfer arthritis mouse model

摘要

Background: Soluble epoxide hydrolase (sEH) is an enzyme that converts epoxyeicosatrienoic acid (EET) into the anti-inflammatory dihydroxyeicosatrienoic acids (DHET). Inhibition of sEH by the potent soluble epoxide hydrolase inhibitor (sEHI) decreases inflammation by increasing EET. The K/BxN serum transfer mouse model of arthritis displays an initial inflammation and an associated tactile allodynia that continues on following the resolution of inflammation. Methods: We undertook the following studies: i) Using the K/BxN mouse model, we examined effects on allodynia during the early inflammatory phase of administration of sEHI 3 mg/kg and/or diclofenac (DFC) 10 mg/kg. ii) In the late inflammatory phase, we administered sEHI (3, 10, or 30 mg/kg); DFC 10 mg/kg; gabapentin 100 mg/kg. iii) Using the conditioned place preference (CPP) we examined the synergism between sEHI and DFC in the K/BxN mouse using the CPP paradigm. The drug was administered intraperitoneally and the allodynia was measured with the von Frey test. Results: In the early phase, both sEHI and DFC displayed an antiallodynic action. In the late phase, sEHI, and gabapentin but not DFC were effective in reversing the allodynia. Comparable results were observed with the CPP. Conclusions: This study demonstrates that sEHI reduces mechanical allodynia in both the early and the late inflammatory K/BxN mouse model of arthritis. The sEHI target thus addresses the hyperalgesia arising from inflammation as well as the post-inflammatory phase that has been said to reflect neuropathic-like states, thus presenting alternatives to the limited efficacy of arthritis drugs in use.