Dextrorphan attenuates responses of spinothalamic tract cells in normal and nerve-injured monkeys

doi:10.1016/S0304-3940(97)00446-1

Neuroscience Letters

Volume 229, Issue 3, 4 July 1997, Pages 169-172

https://doi.org/10.1016/S0304-3940(97)00446-1 Get rights and content

Abstract

Spinal cord N-methyl-d-aspartate (NMDA) receptors play an important role in the transmission of acute and chronic pain. The present study investigated the ability of dextrorphan (DEX), a metabolite of dextromethorphan and a clinically safe NMDA antagonist, to attenuate the responses of nociceptive spinothalamic tract (STT) neurons in anesthetized monkeys. The STT cells were recorded extracellularly in the lumbosacral enlargement and were identified by antidromic activation from the ventral posterior lateral thalamic nucleus. DEX administered through a microdialysis fiber inserted into the dorsal horn inhibited the responses of STT cells in normal animals to noxious pinch and heat stimuli. In monkeys made neuropathic by tight ligation of the L7 or S1 spinal nerve, DEX significantly attenuated the responses of STT cells to noxious pinch and heat, as well as to innocuous brushing, pressure and von Frey filament stimuli. These findings strongly suggest that DEX should be considered a potentially useful therapeutic agent for the treatment of neuropathic pain in humans.

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Acknowledgements

The authors would like to thank Brenda Kenworthy for her secretarial help in preparing the manuscript. The work was supported by NIH grants NS11255, NS27910 (SMC) and NS09743 (WDW) and a Human Frontier Research Fellowship (HR).

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The present study also confirms that tight ligation of spinal nerve L7 in primates leads to increased responsiveness of STT neurons to mechanical and thermal stimuli in the spinal segments just rostral to L7 (Palecek et al., 1992). The electrophysiological data, together with behavioral findings demonstrating enhanced responses to innocuous stimuli (Carlton et al., 1994, 1997, 1998), are consistent with the presence of allodynia in these spinal nerve-lesioned animals. Blocking kainate receptors in awake, behaving animals could conceivably be antiallodynic and antihyperalgesic, as shown for peripheral inflammation with complete Freunds adjuvant in rats (Guo et al., 2002).
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Dextrorphan attenuates responses of spinothalamic tract cells in normal and nerve-injured monkeys

Abstract

Section snippets

Acknowledgements

Brain Res.

Pain

Brain Res.

Eur. J. Pharmacol.

Pain

Brain Res.

Pain

Neurosci. Lett.

Brain Res.

Brain Res. Bull.

Dextromethorphan: an overview of safety issues

Drug Safety

Comparative pharmacology of levorphan, racemorphan, dextrorphan and related methyl ethers

J. Pharmacol. Exp. Ther.