» Articles » PMID: 21686074

Targeting N-methyl-D-aspartate Receptors for Treatment of Neuropathic Pain

Overview
Specialty Pharmacology
Date 2011 Jun 21
PMID 21686074
Citations 88
Authors
Affiliations
Soon will be listed here.
Abstract

Neuropathic pain remains a major clinical problem and a therapeutic challenge because existing analgesics are often ineffective and can cause serious side effects. Increased N-methyl-d-aspartate receptor (NMDAR) activity contributes to central sensitization in certain types of neuropathic pain. NMDAR antagonists can reduce hyperalgesia and allodynia in animal models of neuropathic pain induced by nerve injury and diabetic neuropathy. Clinically used NMDAR antagonists, such as ketamine and dextromethorphan, are generally effective in patients with neuropathic pain, such as complex regional pain syndrome and painful diabetic neuropathy. However, patients with postherpetic neuralgia respond poorly to NMDAR antagonists. Recent studies on identifying NMDAR-interacting proteins and molecular mechanisms of increased NMDAR activity in neuropathic pain could facilitate the development of new drugs to attenuate abnormal NMDAR activity with minimal impairment of the physiological function of NMDARs. Combining NMDAR antagonists with other analgesics could also lead to better management of neuropathic pain without causing serious side effects.

Citing Articles

Current and Evolving Concepts in the Management of Complex Regional Pain Syndrome: A Narrative Review.

Candan B, Gungor S Diagnostics (Basel). 2025; 15(3).

PMID: 39941283 PMC: 11817358. DOI: 10.3390/diagnostics15030353.


Astaxanthin has a beneficial influence on pain-related symptoms and opioid-induced hyperalgesia in mice with diabetic neuropathy-evidence from behavioral studies.

Ciapala K, Pawlik K, Ciechanowska A, Makuch W, Mika J Pharmacol Rep. 2024; 76(6):1346-1362.

PMID: 39528765 PMC: 11582234. DOI: 10.1007/s43440-024-00671-9.


Therapeutic Implication of miRNAs as an Active Regulatory Player in the Management of Pain: A Review.

Hassan M, Shahzadi S, Yasir M, Chun W, Kloczkowski A Genes (Basel). 2024; 15(8).

PMID: 39202362 PMC: 11353898. DOI: 10.3390/genes15081003.


Selective inhibitor of sodium-calcium exchanger, SEA0400, affects NMDA receptor currents and abolishes their calcium-dependent block by tricyclic antidepressants.

Boikov S, Karelina T, Sibarov D, Antonov S Front Pharmacol. 2024; 15:1432718.

PMID: 39156114 PMC: 11327140. DOI: 10.3389/fphar.2024.1432718.


FTY720/Fingolimod mitigates paclitaxel-induced Sparcl1-driven neuropathic pain and breast cancer progression.

Singh S, Weigel C, Brown R, Green C, Tuck C, Salvemini D FASEB J. 2024; 38(15):e23872.

PMID: 39126272 PMC: 11607628. DOI: 10.1096/fj.202401277R.


References
1.
Nowak L, Bregestovski P, Ascher P, Herbet A, Prochiantz A . Magnesium gates glutamate-activated channels in mouse central neurones. Nature. 1984; 307(5950):462-5. DOI: 10.1038/307462a0. View

2.
Liu H, Mantyh P, Basbaum A . NMDA-receptor regulation of substance P release from primary afferent nociceptors. Nature. 1997; 386(6626):721-4. DOI: 10.1038/386721a0. View

3.
Matsuda K, Kamiya Y, Matsuda S, Yuzaki M . Cloning and characterization of a novel NMDA receptor subunit NR3B: a dominant subunit that reduces calcium permeability. Brain Res Mol Brain Res. 2002; 100(1-2):43-52. DOI: 10.1016/s0169-328x(02)00173-0. View

4.
Christoph T, Reissmuller E, Schiene K, Englberger W, Chizh B . Antiallodynic effects of NMDA glycine(B) antagonists in neuropathic pain: possible peripheral mechanisms. Brain Res. 2005; 1048(1-2):218-27. DOI: 10.1016/j.brainres.2005.04.081. View

5.
Schwartzman R, Alexander G, Grothusen J, Paylor T, Reichenberger E, Perreault M . Outpatient intravenous ketamine for the treatment of complex regional pain syndrome: a double-blind placebo controlled study. Pain. 2009; 147(1-3):107-15. DOI: 10.1016/j.pain.2009.08.015. View