Redox manipulation of NMDA receptors in vivo: Alteration of acute pain transmission and dynorphin-induced allodynia

T. M. Laughlin, K. F. Kitto, G. L. Wilcox

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23 Scopus citations


The redox modulatory site of the N-methyl-D-aspartate (NMDA) receptor directly regulates NMDA receptor function. Sulfhydryl reducing agents, such as dithiothreitol (DTT), potentiate NMDA receptor-evoked currents in vitro, whereas oxidizing agents, such as 5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB), attenuate these currents. In this study, we examined the effect of this redox manipulations on nociceptive spinal cord signaling in mice. Intrathecal (i.t.) administration of DTT (0.1-30 nmol), presumably reducing the NMDA receptor, dose-dependently enhanced NMDA-induced nociceptive behaviors, and this enhancement was blocked by the oxidizing agent, DTNB. Pretreatment with DTT (10 nmol, i.t.) enhanced NMDA-induced tail-flick thermal hyperalgesia and intraplantar formalin-induced nociceptive behaviors. Finally, DTT pretreatment enhanced the long lasting allodynia induced by i.t. administration of dynorphin, whereas post-treatment with DTNB reduced the permanent allodynia induced by dynorphin for 5 days. Potentiation of all four of these NMDA-dependent nociceptive behaviors by DTT suggests that the reduction of the NMDA receptor by endogenous reducing agents may contribute to augmented pain transmission in response to activation by endogenous glutamate. Moreover, blockade of in vivo NMDA receptor reducing agents or oxidation of the NMDA receptor redox site may prove therapeutically useful in the treatment of chronic pain. Copyright (C) 1999 International Association for the Study of Pain.

Original languageEnglish (US)
Pages (from-to)37-43
Number of pages7
Issue number1-2
StatePublished - Mar 1 1999

Bibliographical note

Funding Information:
We thank Oanh Nguyen and Ivan Posthumus for outstanding technical support, and Laura S. Stone for her comments on this manuscript. Supported by NIDA/R01-DA-04274 to G.L.W., NIDA training grant T32 DA07097 supported T.M.L.

Copyright 2007 Elsevier B.V., All rights reserved.


  • Dynorphin
  • Hyperalgesia
  • N-methyl-D-aspartate receptor
  • Neuropathic pain
  • Redox
  • Spinal cord


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