Acute Pain After Total Knee Arthroplasty: 2-Arachidonoylglycerol Tone and Endocannabinoid/Eicosanoid Crosstalk
Authors' conclusion
Our findings demonstrate that patients presenting with an elevated 2-AG tone develop greater postoperative pain and position MAGL as an enzymatic node linking 2-AG metabolism with eicosanoid biosynthesis in perioperative human tissue.
Study context
- Population
- Patients undergoing total knee arthroplastyenrolled
- Participants
- 90 patients
- Outcome
- Association of intraoperative 2-AG levels in synovial fluid (SF) and CSF with acute postoperative pain at rest and with ambulation
Methodological detailsex vivo synovial tissue analysis
- Ex vivo synovial tissue analysis
Main finding
As reported in the abstract
Correlation of 2-AG with acute postoperative pain
- Synovial fluid (SF) 2-AG vs pain at rest: r = 0.2644; P = .0157
- SF 2-AG vs pain with ambulation: r = 0.3856; P = .0005
- Cerebrospinal fluid (CSF) 2-AG vs pain at rest: r = 0.3312; P = .0017
- CSF 2-AG vs pain with ambulation: r = 0.1454; P = .1871 (not associated)
Observational data: associations, not effects.
Further findings
Synovial membrane 2-AG levels ex vivo, MAGL inhibition
P = 0.0269
Synovial membrane PGE 2 levels ex vivo, MAGL inhibition
P = 0.0425
- Synovial membrane 2-AG levels ex vivo, monoacylglycerol lipase (MAGL) inhibition: coexpression of MAGL and cyclooxygenase-2 in synovial membranes
2-AG vs pain by sex (subgroup)
- Positive correlations between 2-AG and pain in females, markedly weaker or not observed in males
Original publication
Acute Pain After Total Knee Arthroplasty: 2-Arachidonoylglycerol Tone and Endocannabinoid/Eicosanoid Crosstalk. Anesth Analg. Published 9 September 2025. doi:10. 1213/ ane. 0000000000007741
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