The role of soluble epoxide hydrolase in osteoarthritis pain
Research type
Research Study
Full title
Targeting the therapeutic potential of soluble epoxide hydrolase for the treatment of osteoarthritis pain.
IRAS ID
333889
Contact name
Tom Kurien
Contact email
Sponsor organisation
University of Nottingham
Duration of Study in the UK
2 years, 6 months, 31 days
Research summary
Osteoarthritis (OA) affects ~10 million adults in the UK, damaging multiple inter-connecting joint tissues. Inflammation of the joint lining (synovium), which contains nerves that detect painful signals, involves substances which promote swelling and pain, and other substances which inhibit these processes to allow healing.
Our research is focused on a group of molecules (EETs) that reduce inflammation and pain. We showed that people with lower levels of EETs and higher levels of the inactive metabolites (DHETs) have more severe OA pain and greater progression of OA joint damage.EETs are metabolised by the enzyme soluble epoxide hydrolase (sEH). We found that levels of this enzyme in the synovium are higher in people with painful OA, and we have linked small genetic differences (variants) in the gene (EPHX2) for sEH to the amount of OA pain people experience.
Hypothesis: the effectiveness of sEH in breaking-down the beneficial EET molecules into their inactive metabolites contributes to the amount of OA pain people experience, providing an opportunity for new targeted treatments.
Here, we will determine the cellular processes by which knee joint sEH contributes to OA inflammation and pain, and demonstrate the analgesic properties and therapeutic potential of directly and locally inhibiting this enzyme.
REC name
London - Fulham Research Ethics Committee
REC reference
25/PR/0611
Date of REC Opinion
10 Jun 2025
REC opinion
Further Information Favourable Opinion