The Journal of Neurophysiology Vol. 83 No. 4 April 2000, pp. 2412-2420
Copyright ©2000 by the American Physiological Society

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

Department of Human and Artificial Intelligence Systems, Fukui University, Fukui 910, Japan

Ikeda, Hiroshi, Tatsuya Asai, and Kazuyuki Murase. Robust Changes of Afferent-Induced Excitation in the Rat Spinal Dorsal Horn After Conditioning High-Frequency Stimulation. J. Neurophysiol. 83: 2412-2420, 2000. We investigated the neuronal plasticity in the spinal dorsal horn and its relationship with spinal inhibitory networks using 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 lamina II (the substantia gelatinosa) of 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 neuronal excitation along the slice-depth, was depressed by 28% for more than 1 h after a high-frequency conditioning stimulation of A fibers in the dorsal root (3 tetani of 100 Hz for 1 s with an interval of 10 s). The depression was not induced in a perfusion solution containing an NMDA antagonist, DL-2-amino-5-phosphonovaleric acid (AP5; 30 µM). In a solution containing the inhibitory amino acid antagonists bicuculline (1 µM) and strychnine (3 µM), and also in a low Cl solution, the excitation evoked by the single-pulse stimulation was enhanced after the high-frequency stimulation by 31 and 18%, respectively. The enhanced response after conditioning was depotentiated by a low-frequency stimulation of A fibers (0.2-1 Hz for 10 min). Furthermore, once the low-frequency stimulation was applied, the high-frequency conditioning could not potentiate the excitation. Inhibitory transmissions thus regulate the mode of synaptic plasticity in the lamina II most likely at afferent terminals. The high-frequency conditioning elicits a long-term depression (LTD) of synaptic efficacy under a greater activity of inhibitory amino acids, but it results in a long-term potentiation (LTP) when inhibition is reduced. The low-frequency preconditioning inhibits the potentiation induction and maintenance by the high-frequency conditioning. These mechanisms might underlie robust changes of nociception, such as hypersensitivity after injury or inflammation and pain relief after electrical or cutaneous stimulation.