The Journal of Neurophysiology Vol. 82 No. 4 October 1999, pp. 1957-1964
Copyright ©1999 by the American Physiological Society

Robust Suppression of Afferent-Induced Excitation in the Rat Spinal Dorsal Horn After Conditioning Low-Frequency Stimulation

Hiroshi Ikeda,¹ Tatsuya Asai,¹ Mirjana Randi,² and Kazuyuki Murase¹

 ¹Department of Human and Artificial Intelligent Systems, Fukui University, Fukui 910, Japan; and  ²Department of Biomedical Sciences, Iowa State University, Ames, Iowa 50011

Ikeda, Hiroshi, Tatsuya Asai, Mirjana Randi, and Kazuyuki Murase. Robust Suppression of Afferent-Induced Excitation in the Rat Spinal Dorsal Horn After Conditioning Low-Frequency Stimulation . J. Neurophysiol. 82: 1957-1964, 1999. The neuronal plasticity in the spinal dorsal horn induced after conditioning low-frequency stimulation of afferent A fibers, and its relationship with spinal inhibitory networks, was investigated with an optical-imaging method that detects neuronal excitation. High-intensity single-pulse stimulation of the dorsal root activating both A and C fibers evoked an optical response in the dorsal horn in transverse slices of 12- to 25-day-old rat spinal cords stained with a voltage-sensitive dye, RH-482. The optical response, reflecting the net excitation of neuronal elements along the thickness of each slice, was suppressed after a conditioning low-frequency stimulation (0.2-1 Hz for 10 min) to A fibers in the dorsal root. The degree of suppression was largest in the lamina II of the dorsal horn (48% reduction), where the majority of C fibers terminate, and much less in the deeper dorsal horn (5% reduction in laminae III-IV). The onset of suppression was somewhat slow; after the low-frequency stimulation, the magnitude of excitation gradually decreased, reached the maximum effect 30 min after the conditioning, and remained at the suppressed level for >1 h. Suppression was not observed when the low-frequency stimulation was given during a 20-min perfusion with a solution containing an NMDA-receptor antagonist, DL-2-amino-5-phosphonovaleric acid (30 µM). A brief application of an opioid-receptor antagonist, naloxone (0.5 µM), inhibited the induction, but not the maintenance, of low-frequency stimulus-induced suppression. However, treatments with the GABA_A receptor antagonist bicuculline (1 µM) and the glycine receptor antagonist strychnine (0.3 µM) did not affect suppression induction and maintenance. In conclusion, conditioning low-frequency stimulation to A fibers interferes with the afferent-induced excitation in the dorsal horn. The low-frequency stimulation-induced suppression is maintained by a reduction of glutamatergic excitatory transmissions in the dorsal horn, not by an enhanced inhibition. Activation of the spinal opioid-mediated system by low-frequency stimulation, but not the inhibitory amino acid-mediated system, is necessary to initiate robust suppression. The long-term depression of afferent synaptic efficacy onto excitatory interneurons likely takes the primary role in the robust suppression of neuronal excitation in the dorsal horn.