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      Effects of Perioperative Magnesium Sulfate Administration on Postoperative Chronic Knee Pain in Patients Undergoing Total Knee Arthroplasty: A Retrospective Evaluation


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          We aimed to investigate whether perioperative magnesium sulfate administration was associated with the incidence of chronic persistent postoperative pain (PPP) following total knee arthroplasty (TKA). This retrospective observational study was performed at a single tertiary academic hospital. We reviewed the medical records of adult patients who were admitted between August 2012 and July 2017. Patients who received magnesium sulfate during surgery were the magnesium group. The presence of PPP, one year after TKA, was evaluated using a binary logistic regression analysis. A total of 924 patients were included in the analysis, and 148 patients (16.0%) experienced PPP one year after TKA. In the multivariable model, the magnesium group had a 62% lower rate of PPP one year after TKA compared to the control group (odds ratio (OR): 0.38, 95% confidence interval (CI): 0.16 to 0.90; p = 0.027). This finding was similar in the sensitivity analysis using propensity score adjustment (OR: 0.38, 95% CI: 0.16 to 0.93; p = 0.036). We showed that perioperative magnesium sulfate administration was associated with a lower rate of PPP one year after TKA. Our results suggest that magnesium sulfate administered perioperatively is effective for the alleviation of acute and chronic pain after surgery.

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          N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels widely expressed in the central nervous system that play key roles in excitatory synaptic transmission. Because of their involvement in numerous neurological disorders, NMDARs are also targets of therapeutic interest. NMDARs occur as multiple subtypes which differ in their subunit composition and in their biophysical and pharmacological properties. In particular, NMDARs contain a diversity of sites at which endogenous ligands or pharmacological agents can act to modulate receptor activity in a subunit-selective manner, and recent structural and functional data have started to reveal the molecular determinants for this subunit selectivity. These include the binding sites for glutamate, the ion-channel pore and the recently identified allosteric sites on the N-terminal domain. Other potential sites yet unexplored by medicinal chemistry programs are also considered, in particular at the interface between subunits. Given the growing body of evidence that diverse brain disorders implicate different NMDAR subtypes, such as NR2B in pain or NR3A in white matter injury, there is a growing interest in exploiting the pharmacological heterogeneity of NMDARs for the development of novel NMDAR subtype-selective compounds.
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            In the last decade, the number of total knee replacements performed annually in the United States has doubled, with disproportionate increases among younger adults. While total knee replacement is a highly effective treatment for end-stage knee osteoarthritis, total knee replacement recipients can experience persistent pain and severe complications. We are aware of no current estimates of the prevalence of total knee replacement among adults in the U.S.
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              Persistent Postsurgical Pain: Pathophysiology and Preventative Pharmacologic Considerations.

              The development of chronic pain is considered a major complication after surgery. Basic science research in animal models helps us understand the transition from acute to chronic pain by identifying the numerous molecular and cellular changes that occur in the peripheral and central nervous systems. It is now well recognized that inflammation and nerve injury lead to long-term synaptic plasticity that amplifies and also maintains pain signaling, a phenomenon referred to as pain sensitization. In the context of surgery in humans, pain sensitization is both responsible for an increase in postoperative pain via the expression of wound hyperalgesia and considered a critical factor for the development of persistent postsurgical pain. Using specific drugs that block the processes of pain sensitization reduces postoperative pain and prevents the development of persistent postoperative pain. This narrative review of the literature describes clinical investigations evaluating different preventative pharmacologic strategies that are routinely used by anesthesiologists in their daily clinical practices for preventing persistent postoperative pain. Nevertheless, further efforts are needed in both basic and clinical science research to identify preclinical models and novel therapeutics targets. There remains a need for more patient numbers in clinical research, for more reliable data, and for the development of the safest and the most effective strategies to limit the incidence of persistent postoperative pain.

                Author and article information

                J Clin Med
                J Clin Med
                Journal of Clinical Medicine
                17 December 2019
                December 2019
                : 8
                : 12
                : 2231
                [1 ]Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea; airohtak@ 123456hotmail.com (T.K.O.); jinul8282@ 123456snubh.org (J.P.); medidoc@ 123456nate.com (H.S.)
                [2 ]Department of Orthopedic Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Korea; ccbknee@ 123456snubh.org
                [3 ]TK Orthopedic Surgery, Seongnam 13533, Korea; osktk2000@ 123456yahoo.com
                [4 ]Department of Anesthesiology and Pain Medicine, College of Medicine, Seoul National University, Seoul 03080, Korea
                Author notes
                [* ]Correspondence: shdo@ 123456snu.ac.kr

                These authors have made an equal contribution and should be considered co-first authors.

                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                : 11 November 2019
                : 16 December 2019

                analgesia,spinal anesthesia,total knee arthroplasty,magnesium sulfate,chronic pain


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