KETAMINE AS AN OPTIONAL TREATMENT IN CHRONIC PAIN - A REVIEW
Abstract
Chronic pain is a pervasive and debilitating condition that affects millions of individuals worldwide. Traditional methods of pain management, including the use of opioids, often fall short in providing adequate relief and come with significant risks, such as dependency and tolerance. As a result, there has been growing interest in exploring alternative treatments, with ketamine emerging as a promising option. Ketamine, a dissociative anesthetic, has shown potential in alleviating various types of chronic pain, including neuropathic pain, cancer-related pain, and pain associated with complex regional pain syndrome (CRPS).
Aim of study: This review aims to examine the current evidence on the efficacy of ketamine in chronic pain management, exploring its mechanisms of action, clinical applications, safety profile, and potential limitations.
Methods and materials: PubMed and Scopus databases were used to search for topic treated articles.
References
Cohen, S. P., Vase, L., & Hooten, W. M. (2021). Chronic pain: An update on burden, best practices, and new advances. Lancet, 397(10289), 2082–2097. https://doi.org/10.1016/S0140-6736(21)00393-7
Guven Kose, S., Kose, H. C., Celikel, F., Tulgar, S., De Cassai, A., Akkaya, O. T., & Hernandez, N. (2022). Chronic pain: An update of clinical practices and advances in chronic pain management. Eurasian Journal of Medicine, 54(Suppl 1), 57–61. https://doi.org/10.5152/eurasianjmed.2022.22307
Hawker, G. A., Mian, S., Kendzerska, T., & French, M. (2011). Measures of adult pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short‑Form McGill Pain Questionnaire (SF‑MPQ), Chronic Pain Grade Scale (CPGS), Short Form‑36 Bodily Pain Scale (SF‑36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP). Arthritis Care & Research (Hoboken), 63(Suppl 11), S240–S252. https://doi.org/10.1002/acr.20543
Von Korff, M., DeBar, L. L., Krebs, E. E., Kerns, R. D., Deyo, R. A., & Keefe, F. J. (2020). Graded chronic pain scale revised: Mild, bothersome, and high‑impact chronic pain. Pain, 161(3), 651–661. https://doi.org/10.1097/j.pain.0000000000001758
Reich, D. L., & Silvay, G. (1989). Ketamine: An update on the first twenty‑five years of clinical experience. Canadian Journal of Anaesthesia, 36(2), 186–197. https://doi.org/10.1007/BF03011442
Visser, E., & Schug, S. A. (2006). The role of ketamine in pain management. Biomedicine & Pharmacotherapy, 60(7), 341–348. https://doi.org/10.1016/j.biopha.2006.06.021
Sinner, B., & Graf, B. M. (2008). Ketamine. In Handbook of Experimental Pharmacology (Vol. 182, pp. 313–333). https://doi.org/10.1007/978‑3‑540‑74806‑9_15
Mion, G., & Villevieille, T. (2013). Ketamine pharmacology: An update (pharmacodynamics and molecular aspects, recent findings). CNS Neuroscience & Therapeutics, 19(6), 370–380. https://doi.org/10.1111/cns.12099
Ihmsen, H., Geisslinger, G., & Schüttler, J. (2001). Stereoselective pharmacokinetics of ketamine: R(–)‑ketamine inhibits the elimination of S(+)‑ketamine. Clinical Pharmacology & Therapeutics, 70(5), 431–438. https://doi.org/10.1067/mcp.2001.119722
Fanta, S., Kinnunen, M., Backman, J. T., & Kalso, E. (2015). Population pharmacokinetics of S‑ketamine and norketamine in healthy volunteers after intravenous and oral dosing. European Journal of Clinical Pharmacology, 71(4), 441–447. https://doi.org/10.1007/s00228-015-1826-y
Peltoniemi, M. A., Hagelberg, N. M., Olkkola, K. T., & Saari, T. I. (2016). Ketamine: A review of clinical pharmacokinetics and pharmacodynamics in anesthesia and pain therapy. Clinical Pharmacokinetics, 55(9), 1059–1077. https://doi.org/10.1007/s40262-016-0383-6
White, P. F., Schüttler, J., Shafer, A., Stanski, D. R., Horai, Y., & Trevor, A. J. (1985). Comparative pharmacology of the ketamine isomers: Studies in volunteers. British Journal of Anaesthesia, 57(2), 197–203. https://doi.org/10.1093/bja/57.2.197
Geisslinger, G., Hering, W., Thomann, P., Knoll, R., Kamp, H. D., & Brune, K. (1993). Pharmacokinetics and pharmacodynamics of ketamine enantiomers in surgical patients using a stereoselective analytical method. British Journal of Anaesthesia, 70(6), 666–671. https://doi.org/10.1093/bja/70.6.666
Hijazi, Y., & Boulieu, R. (2002). Contribution of CYP3A4, CYP2B6, and CYP2C9 isoforms to N‑demethylation of ketamine in human liver microsomes. Drug Metabolism and Disposition, 30(7), 853–858. https://doi.org/10.1124/dmd.30.7.853
Cohen, S. P., Liao, W., Gupta, A., & Plunkett, A. (2011). Ketamine in pain management. Advances in Psychosomatic Medicine, 30, 139–161. https://doi.org/10.1159/000324071
Cohen, S. P., Bhatia, A., Buvanendran, A., Schwenk, E. S., Wasan, A. D., Hurley, R. W., Viscusi, E. R., Narouze, S., Davis, F. N., Ritchie, E. C., Lubenow, T. R., & Hooten, W. M. (2018). Consensus guidelines on the use of intravenous ketamine infusions for chronic pain from the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Regional Anesthesia & Pain Medicine, 43(5), 521–546. https://doi.org/10.1097/AAP.0000000000000808
Bell, R. F., Dahl, J. B., Moore, R. A., & Kalso, E. (2005). Peri‑operative ketamine for acute post‑operative pain: A quantitative and qualitative systematic review (Cochrane review). Acta Anaesthesiologica Scandinavica, 49(10), 1405–1428. https://doi.org/10.1111/j.1399-6576.2005.00814.x
Yang, Y., Maher, D. P., & Cohen, S. P. (2020). Emerging concepts on the use of ketamine for chronic pain. Expert Review of Clinical Pharmacology, 13(2), 135–146. https://doi.org/10.1080/17512433.2020.1717947
Bredlau, A. L., Thakur, R., Korones, D. N., & Dworkin, R. H. (2013). Ketamine for pain in adults and children with cancer: A systematic review and synthesis of the literature. Pain Medicine, 14(10), 1505–1517. https://doi.org/10.1111/pme.12182
Calsina‑Berna, A., Alvaro Pardo, M., Cucurull Salamero, M., Bleda‑Perez, M., Julià‑Torras, J. (2024). Oral ketamine for neuropathic cancer pain. BMJ Supportive & Palliative Care, 13(e3), e968–e970. https://doi.org/10.1136/spcare-2023-004306
Noppers, I., Niesters, M., Swartjes, M., Bauer, M., Aarts, L., Geleijnse, N., Mooren, R., Dahan, A., & Sarton, E. (2011). Absence of long‑term analgesic effect from a short‑term S‑ketamine infusion on fibromyalgia pain: A randomized, prospective, double‑blind, active placebo‑controlled trial. European Journal of Pain, 15(9), 942–949. https://doi.org/10.1016/j.ejpain.2011.03.008
Zekry, O., Gibson, S. B., & Aggarwal, A. (2016). Subanesthetic, subcutaneous ketamine infusion therapy in the treatment of chronic nonmalignant pain. Journal of Pain & Palliative Care Pharmacotherapy, 30(2), 91–98. https://doi.org/10.3109/15360288.2016.1161690
Pickering, G., Pereira, B., Morel, V., Corriger, A., Giron, F., Marcaillou, F., Bidar‑Beauvallot, A., Chandeze, E., Lambert, C., Bernard, L., & Delage, N. (2020). Ketamine and magnesium for refractory neuropathic pain: A randomized, double‑blind, crossover trial. Anesthesiology, 133(1), 154–164. https://doi.org/10.1097/ALN.0000000000003345
Van der Velzen, M. V., Dahan, J. D. C., van Dorp, E. L. A., Mogil, J. S., Hooijmans, C. R., & Dahan, A. (2021).Efficacy of ketamine in relieving neuropathic pain: A systematic review and meta‑analysis of animal studies. Pain, 162(9), 2320–2330. https://doi.org/10.1097/j.pain.0000000000002231
Truin, M., Janssen, S. P., van Kleef, M., & Joosten, E. A. (2011). Successful pain relief in non‑responders to spinal cord stimulation: The combined use of ketamine and spinal cord stimulation. European Journal of Pain, 15(10), 1049.e1–1049.e9. https://doi.org/10.1016/j.ejpain.2011.04.004
Richebé, P., Rivat, C., Rivalan, B., Maurette, P., & Simonnet, G. (2005). Kétamine à faibles doses: Antihyperalgésique, non analgésique [Low doses ketamine: Antihyperalgesic, non‑analgesic]. Annales Françaises d'Anesthésie et de Réanimation, 24(11–12), 1349–1359. https://doi.org/10.1016/j.annfar.2005.07.069
Campbell‑Fleming, J. M., & Williams, A. (2008). The use of ketamine as adjuvant therapy to control severe pain. Clinical Journal of Oncology Nursing, 12(1), 102–107. https://doi.org/10.1188/08.CJON.102-107
Blonk, M. I., Koder, B. G., van den Bemt, P. M., & Huygen, F. J. (2010). Use of oral ketamine in chronic pain management: A review. European Journal of Pain, 14(5), 466–472. https://doi.org/10.1016/j.ejpain.2009.09.005
Orhurhu, V., Orhurhu, M. S., Bhatia, A., & Cohen, S. P. (2019). Ketamine infusions for chronic pain: A systematic review and meta‑analysis of randomized controlled trials. Anesthesia & Analgesia, 129(1), 241–254. https://doi.org/10.1213/ANE.0000000000004185
Sun, W., Zhou, Y., Wang, J., Fu, Y., Fan, J., Cui, Y., Wu, Y., Wang, L., Yu, Y., & Han, R. (2023). Effects of ketamine on chronic postsurgical pain in patients undergoing surgery: A systematic review and meta‑analysis. Pain Physician, 26(3), E111–E122.
Israel, J. E., St Pierre, S., Ellis, E., Hanukaai, J. S., Noor, N., Varrassi, G., Wells, M., & Kaye, A. D. (2021).Ketamine for the treatment of chronic pain: A comprehensive review. Health Psychology Research, 9(1), Article 25535. https://doi.org/10.52965/001c.25535
Treede, R.‑D., Rief, W., Barke, A., Aziz, Q., Bennett, M. I., Benoliel, R., Cohen, M., Evers, S., Finnerup, N. B., First, M. B., Giamberardino, M. A., Kaasa, S., Kosek, E., Lavand'homme, P., Nicholas, M., Perrot, S., Scholz, J., Schug, S., Smith, B. H., Svensson, P., Vlaeyen, J. W. S., & Wang, S.‑J. (2015). A classification of chronic pain for ICD‑11. Pain, 156(6), 1003–1007. https://doi.org/10.1097/j.pain.0000000000000160
Nicholas, M., Vlaeyen, J. W. S., Rief, W., Barke, A., Aziz, Q., Benoliel, R., Cohen, M., Evers, S., Giamberardino, M. A., Goebel, A., Korwisi, B., Perrot, S., Svensson, P., Wang, S.‑J., & Treede, R.‑D. (2019). The IASP classification of chronic pain for ICD‑11: Chronic primary pain. Pain, 160(1), 28–37. https://doi.org/10.1097/j.pain.0000000000001390
Views:
0
Downloads:
0
Copyright (c) 2025 Mathias Spitaleri, Karol Kanon, Filip Kieloch, Julia Głowacka, Agnieszka Fitas, Wojciech Gąska, Karolina Dębek-Kalinowska, Oskar Sienkiel, Wiktor Gąska, Dawid Sewruk

This work is licensed under a Creative Commons Attribution 4.0 International License.
All articles are published in open-access and licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Hence, authors retain copyright to the content of the articles.
CC BY 4.0 License allows content to be copied, adapted, displayed, distributed, re-published or otherwise re-used for any purpose including for adaptation and commercial use provided the content is attributed.