Eric S Schwenk1, Basant Pradhan2, Rohit Nalamasu3, Lucas Stolle4, Irving W Wainer5, Michael Cirullo6, Alexander Olsen7, Joseph V Pergolizzi4, Marc C Torjman7, Eugene R Viscusi7. 1. Department of Anesthesiology, Sidney Kimmel Medical College at Thomas Jefferson University, 111 South 11th Street, Gibbon Building, 8290, Philadelphia, PA, 19107, USA. Eric.Schwenk@jefferson.edu. 2. Psychiatry & Pediatrics, Cooper Medical School of Rowan University, Camden, NJ, USA. 3. Department of Physical Medicine and Rehabilitation, University of Nebraska Medical Center, Omaha, NE, USA. 4. NEMA Research, Inc., Naples, FL, USA. 5. Cooper Medical School, Rowan University, Camden, NJ, USA. 6. Department of Anesthesiology, Thomas Jefferson University Hospital, Philadelphia, PA, USA. 7. Department of Anesthesiology, Sidney Kimmel Medical College at Thomas Jefferson University, 111 South 11th Street, Gibbon Building, 8290, Philadelphia, PA, 19107, USA.
Abstract
PURPOSE OF REVIEW: While ketamine's analgesia has mostly been attributed to antagonism of N-methyl-D-aspartate receptors, evidence suggests multiple other pathways are involved in its antidepressant and possibly analgesic activity. These mechanisms and ketamine's role in the nociplastic pain paradigm are discussed. Animal studies demonstrating ketamine's neurotoxicity have unclear human translatability and findings from key rodent and human studies are presented. RECENT FINDINGS: Ketamine's metabolites, and (2R,6R)-hydroxynorketamine in particular, may play a greater role in its clinical activity than previously believed. The activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and the mammalian target of rapamycin by ketamine are mechanisms that are still being elucidated. Ketamine might work best in nociplastic pain, which involves altered pain processing. While much is known about ketamine, new studies will continue to define its role in clinical medicine. Evidence supporting ketamine's neurotoxicity in humans is lacking and should not impede future ketamine clinical trials.
PURPOSE OF REVIEW: While ketamine's analgesia has mostly been attributed to antagonism of N-methyl-D-aspartate receptors, evidence suggests multiple other pathways are involved in its antidepressant and possibly analgesic activity. These mechanisms and ketamine's role in the nociplastic pain paradigm are discussed. Animal studies demonstrating ketamine's neurotoxicity have unclear human translatability and findings from key rodent and human studies are presented. RECENT FINDINGS:Ketamine's metabolites, and (2R,6R)-hydroxynorketamine in particular, may play a greater role in its clinical activity than previously believed. The activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and the mammalian target of rapamycin by ketamine are mechanisms that are still being elucidated. Ketamine might work best in nociplastic pain, which involves altered pain processing. While much is known about ketamine, new studies will continue to define its role in clinical medicine. Evidence supporting ketamine's neurotoxicity in humans is lacking and should not impede future ketamine clinical trials.
Authors: Rajib K Paul; Nagendra S Singh; Mohammed Khadeer; Ruin Moaddel; Mitesh Sanghvi; Carol E Green; Kathleen O'Loughlin; Marc C Torjman; Michel Bernier; Irving W Wainer Journal: Anesthesiology Date: 2014-07 Impact factor: 7.892
Authors: Michael S Avidan; Hannah R Maybrier; Arbi Ben Abdallah; Eric Jacobsohn; Phillip E Vlisides; Kane O Pryor; Robert A Veselis; Hilary P Grocott; Daniel A Emmert; Emma M Rogers; Robert J Downey; Heidi Yulico; Gyu-Jeong Noh; Yonghun H Lee; Christine M Waszynski; Virendra K Arya; Paul S Pagel; Judith A Hudetz; Maxwell R Muench; Bradley A Fritz; Witold Waberski; Sharon K Inouye; George A Mashour Journal: Lancet Date: 2017-05-30 Impact factor: 79.321
Authors: Steven P Cohen; Anuj Bhatia; Asokumar Buvanendran; Eric S Schwenk; Ajay D Wasan; Robert W Hurley; Eugene R Viscusi; Samer Narouze; Fred N Davis; Elspeth C Ritchie; Timothy R Lubenow; William M Hooten Journal: Reg Anesth Pain Med Date: 2018-07 Impact factor: 6.288
Authors: Eric S Schwenk; Eugene R Viscusi; Asokumar Buvanendran; Robert W Hurley; Ajay D Wasan; Samer Narouze; Anuj Bhatia; Fred N Davis; William M Hooten; Steven P Cohen Journal: Reg Anesth Pain Med Date: 2018-07 Impact factor: 6.288