title: Endocannabinoids and acute pain after total knee arthroplasty.
abstract: Osteoarthritis (OA) of the knee is a progressive disease that is associated with inflammation of the joints and lower extremity pain. Total knee arthroplasty (TKA) is a surgical procedure that aims to reduce pain and restore motor function in patients suffering from OA. The immediate postoperative period can be intensely painful leading to extended recovery times including persistent pain. The endocannabinoid system regulates nociception, and the activation of cannabinoid receptors produces antinociceptive effects in preclinical models of OA. To date, the influence of the endocannabinoid tone on pain and disability in OA patients and on acute postoperative pain in humans has not been explored. In this study, we provide the first comprehensive profile of endocannabinoids in serum, cerebrospinal fluid, and synovial fluid of patients with painful end-stage OA undergoing TKA and examine correlations between endocannabinoid levels, interleukin 6, functional disability, acute postoperative pain, and postoperative opioid use. Our results reveal that central (cerebrospinal fluid) and peripheral (synovial fluid) levels of the endocannabinoid 2-arachidonoyl glycerol were significantly elevated in patients who developed higher postoperative pain after TKA. In addition, synovial fluid 2-arachidonoyl glycerol levels were positively correlated with postoperative opioid use. Similarly, synovial fluid levels of the anti-inflammatory lipid palmitoylethanolamide correlated with functional disability in OA. Taken together, our results are the first to reveal associations between central and peripheral endocannabinoid levels and postoperative pain. This suggests that endocannabinoid metabolism may serve as a target for the development of novel analgesics both for systemic or local delivery into the joint.
authors.affiliation: Department of Anesthesiology, Stony Brook University, Stony Brook, NY, USA Department of Orthopedic Surgery, Stony Brook University, Stony Brook, NY, USA Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY, USA National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
authors.forename: Syed
authors.initials: S
authors.lastname: Azim
authors.forename: James
authors.initials: J
authors.lastname: Nicholson
authors.forename: Mario J
authors.initials: MJ
authors.lastname: Rebecchi
authors.forename: William
authors.initials: W
authors.lastname: Galbavy
authors.forename: Tian
authors.initials: T
authors.lastname: Feng
authors.forename: Ruth
authors.initials: R
authors.lastname: Reinsel
authors.forename: Nora D
authors.initials: ND
authors.lastname: Volkow
authors.forename: Helene
authors.initials: H
authors.lastname: Benveniste
authors.forename: Martin
authors.initials: M
authors.lastname: Kaczocha
mesh_terms: D059787:Acute Pain / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000378:metabolism*; D000368:Aged; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects* / Q000639:trends; D015415:Biomarkers / Q000134:cerebrospinal fluid / Q000378:metabolism; D063388:Endocannabinoids / Q000134:cerebrospinal fluid / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010149:Postoperative Pain / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000378:metabolism*; D011446:Prospective Studies; D013582:Synovial Fluid / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D063388:Endocannabinoids