Chronic pain caused by osteoarthritis (OA) is a major clinical problem.
Existing analgesics usually have limited effective effects and / or adverse effects, so new therapies need to be developed
.
Existing analgesics usually have limited effective effects and / or adverse effects, so new therapies need to be developed
.
Epoxyeicosatrienoic acid (EETs) is an endogenous anti-inflammatory mediator, which can be rapidly metabolized to dihydroxyeicosatrienoic acid (DHETs) by soluble epoxide hydrolase (sEH ) .
The research team hypothesized that sEH- driven metabolism of EETs to DHETs plays a key role in chronic joint pain associated with OA and can be used as a new therapeutic target .
The research team hypothesized that sEH- driven metabolism of EETs to DHETs plays a key role in chronic joint pain associated with OA and can be used as a new therapeutic target .
Methods: To study the potential associations between chronic knee pain in patients with OA , single nucleotide polymorphisms (SNPs) in the gene encoding sEH , and the levels of EETs and DHETs in the blood circulation .
The Illumina Global BioIT array was used for genome-wide genotyping .
The genetic associations with neuropathic pain characteristics and tenderness detection threshold (PPT) were analyzed using the PLINK software package .
EETs and DHETs in plasma were detected by liquid chromatography-tandem mass spectrometry .
Use a surgically induced OA mouse model to determine the effect of N-[1-(1 -oxopropyl )-4 -piperidinyl ]-N'-( trifluoromethoxy ) phenyl ] urea (TPPU) on sEH The effects of acute and chronic selective inhibition include weight-bearing asymmetry, hind paw retraction threshold, joint histology, and circulating concentrations of EETs and DHETS .
The Illumina Global BioIT array was used for genome-wide genotyping .
The genetic associations with neuropathic pain characteristics and tenderness detection threshold (PPT) were analyzed using the PLINK software package .
EETs and DHETs in plasma were detected by liquid chromatography-tandem mass spectrometry .
Use a surgically induced OA mouse model to determine the effect of N-[1-(1 -oxopropyl )-4 -piperidinyl ]-N'-( trifluoromethoxy ) phenyl ] urea (TPPU) on sEH The effects of acute and chronic selective inhibition include weight-bearing asymmetry, hind paw retraction threshold, joint histology, and circulating concentrations of EETs and DHETS .
Results: In patients with chronic pain in the knee, .
3 th measure of pain (pain in the lower, inner knee pain and pressure pain threshold DETECT fraction) and sEH gene EPHX2 the SNP correlation, and two separate queues, of EETs and DHETs of Circulation level is also related to 3 pain indicators
.
In the mouse OA model, both acute and chronic systemic administration of TPPU reversed established pain behaviors and reduced the circulating levels of 8,9-DHET and 14,15-DHET .
The level of EETs is not affected by TPPU administration .
In the mouse OA model, both acute and chronic systemic administration of TPPU reversed established pain behaviors and reduced the circulating levels of 8,9-DHET and 14,15-DHET .
The level of EETs is not affected by TPPU administration .
Conclusion: The research team's findings support the soluble epoxide hydrolase ( sEH ) osteoarthritis (OA) effect of pain, and show that inhibition of sEH eicosenoic the protection and endogenous ethylene-trienoic acid (EET) Free Catabolism is a potential new therapeutic target for OA pain
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Source:
Gowler PRW, Turnbull J, Shahtaheri M, Gohir S, Kelly T, McReynolds C, Jun Y, Jha RR, Fernandes GS, Zhang W, Doherty M, Walsh DA, Bruce HD, Valdes AM, Barrett DA, Chapman V.
Clinical and preclinical evidence for roles of soluble epoxide hydrolase in osteoarthritis knee pain.
Arthritis Rheumatol.
2021 Oct 21.
doi: 10.
1002/art.
42000.
Epub ahead of print.
PMID: 34672113.
Clinical and preclinical evidence for roles of soluble epoxide hydrolase in osteoarthritis knee pain.
Arthritis Rheumatol.
2021 Oct 21.
doi: 10.
1002/art.
42000.
Epub ahead of print.
PMID: 34672113.
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