Magnesium in pain control - mechanisms of action in perioperative pain, neuropathic pain and migraine
DOI:
https://doi.org/10.12775/JEHS.2025.78.57571Keywords
magnesium, pain, NMDA receptor, perioperative pain, neuropathic pain, migraineAbstract
Introduction
Magnesium is a crucial macroelement with widespread effects on the nervous and muscular systems.. Due to its role as an NMDA receptor antagonist, magnesium has garnered significant attention in pain management research, particularly for its potential to modulate both acute and chronic pain. This article provides an overview of magnesium's therapeutic applications in neuropathic pain, migraine, and perioperative pain, drawing on research from PubMed and Google Scholar published between 1988 and 2025.
Aim of study
This review aims to present the state of knowledge about magnesium’s possible role in pain control and present mechanism of its influence on the nociceptive stimuli reception.
Materials and methods
Publication research was made using databases PubMed and Google Scholar. Keywords used in research were among others: magnesium, pain, neuropathic pain, migraine, perioperative pain, magnesium deficiency.
Current state of knowledge
Magnesium plays a crucial role in the management of various pain conditions, including perioperative, neuropathic, and migraine pain, through its multifactorial mechanisms. These include NMDA receptor antagonism, calcium channel blockade, anti-inflammatory effects, and muscle relaxation, all of which contribute to its analgesic properties. Evidence suggests that magnesium supplementation can reduce opioid use, counteract central and peripheral sensitization, and potentially prevent migraine attacks, highlighting its potential as an effective adjuvant in pain management strategies.
Summary (Conclusions):
Magnesium offers significant therapeutic potential in managing perioperative, neuropathic, and migraine pain through mechanisms such as NMDA receptor antagonism, calcium channel blockade, and neuroinflammation modulation. Its use can reduce opioid consumption, enhance pain relief, and improve outcomes, highlighting the need for further research into its clinical applications in pain management.
References
1. Wilder‐Smith, C. H., R. Knöpfli, and O. H. G. Wilder‐Smith. "Perioperative magnesium infusion and postoperative pain." Acta anaesthesiologica scandinavica 41.8 (1997): 1023-1027.
2. Kwater, Andrzej P., Michael C. Grant, and Tong J. Gan. "Magnesium and Its Emerging Role in Perioperative Pain Management." Anesthesia & Analgesia 140.1 (2025): 51-53.
3. Kara, H., et al. "Magnesium infusion reduces perioperative pain." European journal of anaesthesiology 19.1 (2002): 52-56.
4. Shin, Hyun-Jung, Hyo-Seok Na, and Sang-Hwan Do. "Magnesium and pain." Nutrients 12.8 (2020): 2184.
5. Srebro, Dragana, et al. "Magnesium in pain research: state of the art." Current medicinal chemistry 24.4 (2017): 424-434.
6. Morel, Véronique, et al. "Magnesium for pain treatment in 2021? State of the art." Nutrients 13.5 (2021): 1397.
7. Bujalska-Zadrożny, Magdalena, et al. "Magnesium enhances opioid-induced analgesia–What we have learnt in the past decades?." European Journal of Pharmaceutical Sciences 99 (2017): 113-127.
8. Arumugam, Sudha, Christine SM Lau, and Ronald S. Chamberlain. "Perioperative adjunct magnesium decreases postoperative opioid requirements—a meta-analysis." International Journal of Clinical Medicine 7.5 (2016): 297-308.
9. Murphy, Jamie D., et al. "Analgesic efficacy of continuous intravenous magnesium infusion as an adjuvant to morphine for postoperative analgesia: a systematic review and meta-analysis." Middle East J Anaesthesiol 22.1 (2013): 11-20.
10. Lysakowski, Christopher, et al. "Magnesium as an adjuvant to postoperative analgesia: a systematic review of randomized trials." Anesthesia & Analgesia 104.6 (2007): 1532-1539.
11. Mazur, Andrzej, et al. "Magnesium and the inflammatory response: potential physiopathological implications." Archives of biochemistry and biophysics 458.1 (2007): 48-56.
12. Sugimoto, Jun, et al. "Magnesium decreases inflammatory cytokine production: a novel innate immunomodulatory mechanism." The Journal of Immunology 188.12 (2012): 6338-6346.
13. Maier, Jeanette A., et al. "Magnesium and inflammation: Advances and perspectives." Seminars in cell & developmental biology. Vol. 115. Academic Press, 2021.
14. Turan, Alparslan, et al. "Intravenous regional anesthesia using lidocaine and magnesium." Anesthesia & Analgesia 100.4 (2005): 1189-1192.
15. Soave, P. M., et al. "Magnesium and anaesthesia." Current drug targets 10.8 (2009): 734-743.
16. Sinha, R., et al. "Effect of addition of magnesium to local anesthetics for peribulbar block: A prospective randomized double-blind study." Saudi journal of anaesthesia 10.1 (2016): 64-67.
17. Aissaoui, Younes, et al. "Magnesium sulphate: an adjuvant to tracheal intubation without muscle relaxation–a randomised study." European Journal of Anaesthesiology| EJA 29.8 (2012): 391-397.
18. Do, Sang-Hwan. "Magnesium: a versatile drug for anesthesiologists." Korean journal of anesthesiology 65.1 (2013): 4-8.
19. Gupta, K., V. Vohra, and J. Sood. "The role of magnesium as an adjuvant during general anaesthesia." Anaesthesia 61.11 (2006): 1058-1063.
20. Eizaga Rebollar, Ramón, et al. "Magnesium sulfate in pediatric anesthesia: the Super Adjuvant." Pediatric Anesthesia 27.5 (2017): 480-489.
21. Demirkiran, Hilmi, et al. "The Effect of Midazolam and Magnesium Sulfate on Preoperative Anxiety in Patients Undergoing Rhinoplasty Operation." THE ULUTAS MEDICAL JOURNAL 9.1 (2023): 42-42.
22. Lu, Jing, et al. "Intravenously injected lidocaine or magnesium improves the quality of early recovery after laparoscopic cholecystectomy: a randomised controlled trial." European Journal of Anaesthesiology| EJA 38 (2021): S1-S8.
23. Van Hecke, O. A. S. K. R., et al. "Neuropathic pain in the general population: a systematic review of epidemiological studies." PAIN® 155.4 (2014): 654-662.
24. Smith, Blair H., and Nicola Torrance. "Epidemiology of neuropathic pain and its impact on quality of life." Current pain and headache reports 16 (2012): 191-198.
25. Schreiber, Anne K., et al. "Diabetic neuropathic pain: physiopathology and treatment." World journal of diabetes 6.3 (2015): 432.
26. Sadosky, Alesia, et al. "A review of the epidemiology of painful diabetic peripheral neuropathy, postherpetic neuralgia, and less commonly studied neuropathic pain conditions." Pain Practice 8.1 (2008): 45-56.
27. Schwartzman, Robert J., et al. "Neuropathic central pain: epidemiology, etiology, and treatment options." Archives of Neurology 58.10 (2001): 1547-1550.
28. Meacham, Kathleen, et al. "Neuropathic pain: central vs. peripheral mechanisms." Current pain and headache reports 21 (2017): 1-11.
29. Koltzenburg, Martin, H. Erik Torebjörk, and Lis Karin Wahren. "Nociceptor modulated central sensitization causes mechanical hyperalgesia in acute chemogenic and chronic neuropathic pain." Brain 117.3 (1994): 579-591.
30. Baron, Ralf. "Peripheral neuropathic pain: from mechanisms to symptoms." The Clinical journal of pain 16.2 (2000): S12-S20.
31. Wen, Bei, Li Xu, and Yuguang Huang. "Mechanisms of Peripheral Sensitization in Neuropathic Pain." Translational Research in Pain and Itch (2024): 211-226.
32. Ellis, A., and D. L. H. Bennett. "Neuroinflammation and the generation of neuropathic pain." British journal of anaesthesia 111.1 (2013): 26-37.
33. Myers, Robert R., W. Marie Campana, and Veronica I. Shubayev. "The role of neuroinflammation in neuropathic pain: mechanisms and therapeutic targets." Drug discovery today 11.1-2 (2006): 8-20.
34. Kiguchi, Norikazu, Yuka Kobayashi, and Shiroh Kishioka. "Chemokines and cytokines in neuroinflammation leading to neuropathic pain." Current opinion in pharmacology 12.1 (2012): 55-61.
35. Brill, S., et al. "Efficacy of intravenous magnesium in neuropathic pain." British journal of anaesthesia 89.5 (2002): 711-714.
36. Lin, C. Y., et al. "L-type calcium channels are involved in mediating the anti-inflammatory effects of magnesium sulphate." British journal of anaesthesia 104.1 (2010): 44-51.
37. Zhang, Jun, et al. "The causal role of magnesium deficiency in the neuroinflammation, pain hypersensitivity and memory/emotional deficits in ovariectomized and aged female mice." Journal of inflammation research (2021): 6633-6656.
38. Shahi, Abbas, et al. "The role of magnesium in different inflammatory diseases." Inflammopharmacology 27 (2019): 649-661.
39. Felsby, S., et al. "NMDA receptor blockade in chronic neuropathic pain: a comparison of ketamine and magnesium chloride." Pain 64.2 (1996): 283-291.
40. Ma, Qing-Ping, and Clifford J. Woolf. "The NMDA receptor, pain and central sensitization." NMDA antagonists as potential analgesic drugs (2002): 83-103.
41. Liu, Hong-Tao, et al. "Modulation of NMDA receptor function by ketamine and magnesium: Part I." Anesthesia & Analgesia 92.5 (2001): 1173-1181.
42. Biondi, David M. "Is migraine a neuropathic pain syndrome?." Current Pain and Headache Reports 10 (2006): 167-178.
43. Chakravarty, A., and A. Sen. "Migraine, neuropathic pain and nociceptive pain: Towards a unifying concept." Medical hypotheses 74.2 (2010): 225-231.
44. Dolati, Sanam, et al. "The role of magnesium in pathophysiology and migraine treatment." Biological trace element research 196 (2020): 375-383.
45. Mauskop, Alexander, and Jasmine Varughese. "Why all migraine patients should be treated with magnesium." Journal of neural transmission 119 (2012): 575-579.
46. Domitrz, Izabela, and Joanna Cegielska. "Magnesium as an important factor in the pathogenesis and treatment of migraine—from theory to practice." Nutrients 14.5 (2022): 1089.
47. Chiu, Hsiao-Yean, et al. "Effects of intravenous and oral magnesium on reducing migraine: a meta-analysis of randomized controlled trials." Pain physician 19.1 (2016): E97.
48. Bigal, M. E., et al. "Intravenous magnesium sulphate in the acute treatment of migraine without aura and migraine with aura. A randomized, double-blind, placebo-controlled study." Cephalalgia 22.5 (2002): 345-353.
49. Demirkaya, Şeref, et al. "Efficacy of intravenous magnesium sulfate in the treatment of acute migraine attacks." Headache: The Journal of Head and Face Pain 41.2 (2001): 171-177.
50. Maier, Jeanette A., et al. "Headaches and magnesium: mechanisms, bioavailability, therapeutic efficacy and potential advantage of magnesium pidolate." Nutrients 12.9 (2020): 2660.
51. Boska, M. D., et al. "Contrasts in cortical magnesium, phospholipid and energy metabolism between migraine syndromes." Neurology 58.8 (2002): 1227-1233.
52. Swanson, Don R. "Migraine and magnesium: eleven neglected connections." Perspectives in biology and medicine 31.4 (1988): 526-557.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Anna Konarska, Artur Fabijański, Adriana Dukacz, Wojciech Firlej, Joanna Rychlewska-Duda, Justyna Lisiecka, Michał Nowak, Mateusz Janik, Barbara Ufnalska, Anna Machowiak
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 149
Number of citations: 0
