The Use of NMDA‐Receptor Antagonists in the Treatment of Chronic Pain

  title={The Use of NMDA‐Receptor Antagonists in the Treatment of Chronic Pain},
  author={David J. Hewitt},
  journal={The Clinical Journal of Pain},
  • D. Hewitt
  • Published 1 June 2000
  • Biology, Medicine
  • The Clinical Journal of Pain
Abstract: Chronic pain can be maintained by a state of sensitization within the central nervous system that is mediated in part by the excitatory amino acids glutamate and aspartate binding to the N‐methyl‐D‐aspartate (NMDA) receptor. A number of antagonists to the NMDA receptor are antinociceptive in animal models but are associated with significant dose‐limiting side effects. Commercially available NMDA‐receptor antagonists include ketamine, dextromethorphan, memantine, and amantadine. The… 
The Role of N-Methyl-d-Aspartate (NMDA) Receptors in Pain: A Review
Among NMDA receptor subtypes, the NR2 B subunit-containing receptors appear particularly important for nociception, thus leading to the possibility that NR2B-selective antagonists may be useful in the treatment of chronic pain.
NMDA receptors as targets for drug action in neuropathic pain.
  • C. Parsons
  • Biology
    European journal of pharmacology
  • 2001
Glutamate Receptors and Nociception
Inhibition of glutamate release, or of glutamate receptors, in the spinal cord or periphery attenuates both acute and chronic pain in animal models and similar benefits have been seen in studies involving humans (both patients and volunteers); however, results have been inconsistent.
D-Aspartate Modulates Nociceptive-Specific Neuron Activity and Pain Threshold in Inflammatory and Neuropathic Pain Condition in Mice
The findings suggest that the NMDAR agonist, D-Asp, may play a role in the regulation of NS neuron electrophysiological activity and behavioral responses in physiological and pathological pain conditions.
Low dose of S+-ketamine prevents long-term potentiation in pain pathways under strong opioid analgesia in the rat spinal cord in vivo.
The combination of S(+)-ketamine with fentanyl reveals both a reduction of C-fibre-evoked potentials and prevention of LTP and seem therefore a better choice for perioperative pain management compared with the sole administration.
In vivo activation of the SK channel in the spinal cord reduces the NMDA receptor antagonist dose needed to produce antinociception in an inflammatory pain model
It is demonstrated that in vivo activation of SK channels in the spinal cord can alleviate mechanical hypersensitivity in a rat model of inflammatory pain and reduces the dose of NMDAR antagonist, DL-2-amino-5-phosphonopentanoic acid, required to produce antinociceptive effects in the CFA model.
Spinal leptin contributes to the development of morphine antinociceptive tolerance by activating the STAT3-NMDA receptor pathway in rats.
It is demonstrated for the first time, to the best of the authors' knowledge, that spinal leptin contributes to the development of morphine antinociceptive tolerance by activating the spinal STAT3‑NMDA receptor pathway.