NMDA or non-NMDA receptor antagonists attenuate increased fos expression in spinal dorsal horn gabaergic neurons after intradermal injection of capsaicin in rats

GABAergic neurons play an important role in the generation of primary affer ent depolarization, which results in presynaptic inhibition and, if large e nough, triggers dorsal root reflexes. Recent electrophysiological studies b y our group have suggested that increased excitation of spinal GABAergic ne urons by activation of AT-Methyl-D-aspartate (NMDA) and non-NMDA receptors following intradermal injection of capsaicin results in the generation of D RRs that contribute to neurogenic inflammation. The present study was to de termine if changes in the expression of Fos protein occur in GABAergic neur ons in the lumbosacral spinal cord following injection of capsaicin into th e glabrous skin of one hind paw of anesthetized rats and if pretreatment wi th an NMDA receptor antagonist, D-(-)-2-amino-7-phosphonoheptanoic acid (AP 7) or a non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) blocks Fos expression in these neurons. The experiments used western blots and immunofluorescence double labeling staining following capsaicin or vehicle injection. Western blots showed that Fos protein was increased o n the ipsilateral side in spinal cord tissue 0.5 It after capsaicin injecti on. Pretreatment with AP7 or CNQX caused a decrease in capsaicin-induced Fo s expression. Immunofluorescence double labeling showed that the proportion of Fos-positive GABAergic neuronal profiles was significantly increased fo llowing capsaicin injection (48.8 +/-4.8%) compared to the vehicle injectio n (23.8 +/-5.1%) in superficial laminae on the ipsilateral side in lumbosac ral spinal cord (P <0.05). However, when the spinal cord was pretreated wit h AP7 (5 mug) or CNQX (0.2 mug), only 9.1 +/-0.6% or 7.1 +/-0.8% of GABA-im munoreactive neuronal profiles were stained for Fos following capsaicin inj ection. The blockade of the capsaicin-evoked Fos staining was dose-dependen t. These findings suggest that GABAergic neurons take part in dorsal horn circ uits that modulate nociceptive information and that the function of GABAerg ic neurons following capsaicin injection is partially mediated by NMDA and non-NMDA receptors. (C) 2001 IBRO. Published by Elsevier Science Ltd. All r ights reserved.