title: Dextrorphan attenuates responses of spinothalamic tract cells in normal and nerve-injured monkeys.
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.
authors.affiliation: Department of Anatomy and Neurosciences, Marine Biomedical Institute, University of Texas Medical Branch, Galveston 77555, USA. carlton@mbian.utmb.edu
authors.forename: S M
authors.initials: SM
authors.lastname: Carlton
authors.forename: H
authors.initials: H
authors.lastname: Rees
authors.forename: K
authors.initials: K
authors.lastname: Gondesen
authors.forename: W D
authors.initials: WD
authors.lastname: Willis
mesh_terms: D000818:Animals; D003917:Dextrorphan / Q000494:pharmacology*; D004594:Electrophysiology; D008026:Ligation; D008252:Macaca fascicularis; D008297:Male; D017551:Microdialysis; D008839:Microelectrodes; D018696:Neuroprotective Agents / Q000494:pharmacology*; D013127:Spinal Nerves / Q000187:drug effects / Q000293:injuries* / Q000601:surgery; D013133:Spinothalamic Tracts / Q000166:cytology* / Q000502:physiology
chemical_list: D018696:Neuroprotective Agents; D003917:Dextrorphan