The antiallodynic effect of NMDA antagonists in neuropathic pain outlasts the duration of the in vivo NMDA antagonism

Neuropharmacology
Thomas ChristophB A Chizh

Abstract

Clinical reports have described a long-lasting relief in neuropathic pain patients treated with NMDA receptor antagonists; it is unclear, however, what mediates this effect. In this work, we have used two NMDA antagonists of different class to investigate if the antiallodynic effects in a rat neuropathy model can outlast their in vivo NMDA antagonism. Both the uncompetitive NMDA antagonist ketamine and the glycine(B) antagonist MRZ 2/576 inhibited neuronal responses to iontophoretic NMDA in anaesthetised rats with the time course consistent with their known pharmacokinetics (t(1/2) approximately 10-12min, similar in control and nerve-injured rats). Surprisingly, the antiallodynic effects of the same doses of the NMDA antagonists in the neuropathic pain model were long-lasting (>3h with ketamine, >24h with MRZ 2/576). The effect of ketamine was further prolonged (>24h) when combined with a short-acting opioid, fentanyl, which only produced a short effect ( approximately 40min) when given alone. The duration of centrally mediated side effects of ketamine and MRZ 2/576 was short, similar to the in vivo NMDA antagonism. We speculate that NMDA receptor blockade may down-regulate the central sensitisation triggered by nerve injury, r...Continue Reading

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Citations

Feb 4, 2014·Neuropharmacology·Ruggero G FarielloCarlo Farina
Jun 21, 2011·Expert Review of Clinical Pharmacology·Hong-Yi ZhouHui-Lin Pan
Aug 9, 2012·Expert Opinion on Drug Metabolism & Toxicology·Marieke Niesters, Albert Dahan
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Apr 8, 2014·Fundamental & Clinical Pharmacology·Véronique MorelLaurence Daulhac
Feb 11, 2015·Physiology & Behavior·Ya-Juan ZhaoYong-Jin Chen
Dec 3, 2014·Neuroscience Letters·V A CarozziA Chiorazzi
Jan 16, 2015·Metabolic Brain Disease·Dominic SchombergDaniel Resnick
Jul 1, 2008·Pharmacology, Biochemistry, and Behavior·Joseph R HoltmanElzbieta P Wala
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Mar 13, 2021·Frontiers in Pharmacology·Clayton CulpSalahadin Abdi

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