The Role Of NMDA Receptors In Neurophysiology Of Pain And Modulation

The Role Of NMDA Receptors In Neurophysiology Of Pain And Modulation

Authors

  • Manish Lamoria
  • Soumi H. Chaudhuri
  • Garima Agarwal

Keywords:

NMDA receptor, pain, glutamate, opoid receptor

Abstract

Background & Objective: NMDA is a receptor for the excitatory neurotransmitter glutamate, which is released with noxious peripheral stimuli. The activation of NMDA receptors has been associated with hyperalgesia, neuropathic pain, and reduced functionality of opioid receptors. Hyperalgesia and neuropathic pain are a result of increased spinal neuron sensitization, leading to a heightened level of pain. The reduced function of opioid receptors is caused by a decrease in the opioid receptor's sensitivity. Therefore, NMDA antagonists have a role in these areas of pain management. Ketamine is a strong NMDA antagonist. To study the role of NMDA receptors in pain and modulation by blocking the receptors through antagonist ketamine given pre-emptively and postoperatively via epidural route in patients of lower limb amputation. Methodology: This study was conducted at Civil Hospital Ahmedabad during the year 2012-2015 with the permission of ethical committee of hospital and after written informed consent of 60 adult patients of age group 18- 60 years of either sex and ASA grade 1 or 2 posted for lower limb amputation. Patients were divided into three groups where one was administered epidural opioid and ketamine, the second group was administered epidural opioid only and in the third group epidural saline was administered. Pain scores of all the groups were compared. Results: Requirement of first dose of analgesia in group 1 is after 12.5±1.03hrs, in group 2 after7.6± 0.98 hrs and in group3 after 3.4± 0.8hrs and average duration between consecutive analgesic doses were 11.5hrs in group 1, 7.6hrs in group 2 and 4.5hrs in group 3 respectively. Conclusion: NMDA receptor antagonist is effective in management of acute post-operative pain compared to opioid analgesics alone as the time to first dose of analgesia is much larger in group 1 than 2 and 3. Ketamine has definitive role in opioid sparing effect as supplemental analgesic requirement is decreased. [Lamoria M NJIRM 2015; 7(1):1-6]

References

1. Bennett GJ. Neuropathic pain. In: Wall PD, Melzack R, eds. Textbook of pain, 3rd ed. Edinburgh, London: Churchill Livingstone, 1994:201–224.
2. Meyer RA, Campbell JN, Raja SN. Peripheral neural mechanisms of nociception. In: Wall PD, Melzack R, eds. Textbook of pain, 3rd ed. Edinburgh, London: Churchill Livingstone, 1994:201–224.
3. Devor M. The pathophysiology of damaged peripheral nerves. In: Wall PD, Melzack R, eds. Textbook of pain, 3rd ed. Edinburgh, London: Churchill Livingstone, 1994:201–224.
4. Woolf CJ, Thompson SWN. The induction and maintenance of central sensitization is dependent on N-methyl-D-aspartic acid receptor activation: implications for the treatment of post-injury pain hypersensitivity states. Pain 1991;44:293–299.
5. LaMotte RH, Shain CN, Simone DA, et al. Neurogenic hyperalgesia: psychophysical studies of underlying mechanisms. J Neurophysiol 1991;66:190– 211.
6. Mao J, Price DD, Mayer DJ, Lu J, Hayes RL. Intrathecal MK 801 and local nerve anesthesia synergistically reduce nociceptive behaviors in rats with experimental peripheral mononeuropathy. Brain Res 1992;576:254–262.
7. Chaplan SR, Malmberg AB, Yaksh, TL. Efficacy of spinal NMDA-receptor antagonism in formalin hyperalgesia and nerve injury evoked allodynia in the rat. Pharmacol Exp Therap 1997;280:829–838. 20. Mao J, Price DD, Hayes RL, Lu J, Mayer DJ, Frenk H. Intrathecal treatment with dextrorphan or ketamine potently reduces pain-related behaviours in a rat model of peripheral mononeuropathy. Brain Res 1993;605:164–168.
8. Eide PK, Jorum E, Stubhaug A, et al. Relief of post-herpetic neuralgia with the N-methyl-D-aspartic acid receptor antagonist ketamine: a double-blind, cross-
over comparison with morphine and placebo. Pain 1994;58:347–354.
9. Max MB, Byas-Smith MG, Gracely RH, et al. Intravenous infusion of the NMDA antagonists, ketamine, in chronic post-traumatic pain and allodynia: a double-blind comparison with alfentanil and placebo. Clin Neuropharmacol 1995;18:360–368.
10. Persson J, Axelsson G, Hallin RG, et al. Beneficial effects of ketamine in a chronic pain state with allodynia, possibly due to central sensitization. Pain 1995;60:217–222. 26. Nelson KA, Park KM, Robinovitz E, et al. Highdose oral dextromethorphan versus placebo in painful diabetic neuropathy and postherpetic neuralgia. Neurol 1997;48:1212–1218. 27. Eisenberg E, Pud D. Can patients with chronic neuropathic pain be cured by acute administration of the NMDA-receptor antagonist amantadine? Pain 1994;74:37–39.
11. Abdel-Ghaffar ME, Abdullatif MA, al Ghamdi A et al. Epidural ketamine reduces postoperative epidural PCA consumption of fentanyl/bupivacaine. Can Anaesth Soc J 1998; 45: 103-09.
12. Eugene S.Fu, Rafael M, John E. Scharf. Pre-emptive ketamine decreases postoperative narcotic requirements in patients undergoing abdominal surgery. Anesth Analg 1997; 84: 1086-90.
13. Islas J-A, Astorga J, Laredo M. Epidural ketamine for control of postoperative pain. Anesth Analg 1985; 64: 1161-62.
14. J. Wilson, A. Nimmo, S. Fleetwood-Walker, L. Colvin. A randomised double blind trial of the effect of pre-emptive epidural ketamine on persistent pain after lower limb amputation. Pain, Volume 135, Issue 1, Pages 108-118
15. Kawana Y, Sato H, Shimada H et al. Epidural ketamine for postoperative pain relief after gynaecological operations: a double-blind study and comparison with epidural morphine. Anesth Analg 1987; 66: 735-38.
16. Kinck AD, Ngai SH. Opiate receptor mediation of ketamine analgesia. Anaesthesiology 1982; 56: 291-97.
17. Kitahara LM, Taub A, Kosaka Y. Lamina-specific suppression of dorsal horn unit activity by ketamine hydrochloride. Anaesthesiology 1973; 38: 4-11.
18. Lanlin JP, Maurette P, Corcuff JB et al. The role of ketamine in preventing fentanyl induced hyperalgesia and subsequent acute morphine tolerance – Anesth Analg 2002; 94: 1263-69
19. Dr.Veena R. Shah, Dr. Raj Rawal, Dr. Manish Pre operative effect of epidural buprenorphine with ketamine on postoperative pain after lower urinary tract surgery Indian, JR. Anaesth 2006;50(4)R:E 271-274
20. Wong CS, Liaw WJ, Tung CS et al. Ketamine potentiates analgesic effect of morphine in postoperative epidural pain control. Regional Anesth. 1996; 21: 534-41.
21. Wong CS, Lu CC, Cherng CH, Ho ST. Pre-emptive analgesia with ketamine, morphine and epidural lidocaine prior to total knee replacement. Can Anaesth Soc J 1997; 44: 31-37.
22. Wu CT, Yeh CC, Yu JC, Lee MM, Tao PL, Ho ST, Wong CS. Pre-incisional epidural ketamine, morphine and bupivacaine combined with epidural and general anaesthesia provides pre-emptive analgesia for upper abdominal surgery. ActaAnaesthesiol Scand. 2000 Jan;44(1):63-8
23. Xie H, Wang X, Liu G, Wang G.Clin J Pain. 2003 Sep-Oct;(5):317-22. Analgesic effects and pharmacokinetics of a low dose of ketamine preoperatively administered epidurally or intravenously.
24. YY Chia, K Liu, YC Liu, HC Chang, and CS Wong Adding ketamine in a multimodal patient-controlled epidural regimen reduces postoperative pain and analgesic consumption Anesth Analg 1998 86: 1245-1249.
25. Takekazu Terai, Hidekazu Yukioka1, Osamu Morimoto1 and Mitsugu Fujimori1. Lumbar epidural buprenorphine for postoperative pain relief following hepatectomy. Journal of Anaesthesia, Springer Japan, Volume 8, Number 4 / December, 1994, 410-414.

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Published

2016-02-29

How to Cite

Lamoria, M., Chaudhuri, S. H., & Agarwal, G. (2016). The Role Of NMDA Receptors In Neurophysiology Of Pain And Modulation: The Role Of NMDA Receptors In Neurophysiology Of Pain And Modulation. National Journal of Integrated Research in Medicine, 7(1), 1–6. Retrieved from http://nicpd.ac.in/ojs-/index.php/njirm/article/view/1033

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