Pain medicine

Acute Pain After Total Knee Arthroplasty: 2-Arachidonoylglycerol Tone and Endocannabinoid/Eicosanoid Crosstalk

Anesth AnalgPublished Prospective observational study

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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