Intrathecal treatment with MK-801 suppresses thermal nociceptive responses and prevents c-fos immunoreactivity induced in rat lumbar spinal cord neurons.
Sensitization of the second order neurons in the spinal dorsal horn after somatic noxious stimuli is partly mediated by the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor. These neurons also express c-Fos immunoreactivity in response to the somatic noxious stimuli. The present study assessed the influence of intrathecal pre-treatment with MK-801, a non-competitive antagonist of NMDA receptor, on thermal sensitization following peripheral noxious heat stimulation. In addition, the influence of MK-801 on c-Fos immunoreactivity in the rat lumbar spinal cord neurons after the peripheral noxious heat was examined. Sprague-Dawley rats were subject to intrathecal catheterization and administration of MK-801 or saline before and after noxious heat (52 degrees C) stimulation of rat hindpaws. Thermal sensitization was tested after MK-801 (0.1 mumol 10 microliters-1). Fos-like immunoreactivity was evaluated 2 h after noxious stimulation in a separate group of animals. MK-801 significantly increased the thermal withdrawal threshold by 60% following noxious heat stimulation and reduced c-Fos immunoreactivity in the second order neurons by 70% in the dorsal horn. The study suggests that glutamate plays a pivotal role in the thermal nociceptive pathway and indicates that the NMDA receptor is necessary to maintain normal thermal sensitization, possibly by regulating c-fos gene expression in second order neurons.
Huang
W
W
Department of Neurosurgery, Baylor College of Medicine, Houston 77030, USA.
Simpson
R K
RK
D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010147:Pain Measurement / Q000187:drug effects*; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000276:immunology* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
D018691:Excitatory Amino Acid Antagonists; D016760:Proto-Oncogene Proteins c-fos; D016291:Dizocilpine Maleate