Robust changes of afferent-induced excitation in the rat spinal dorsal horn after conditioning high-frequency stimulation.
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 microM). In a solution containing the inhibitory amino acid antagonists bicuculline (1 microM) and strychnine (3 microM), 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.
Ikeda
H
H
Department of Human and Artificial Intelligence Systems, Fukui University, Fukui 910, Japan.
Asai
T
T
Murase
K
K
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002712:Chlorides / Q000493:pharmacokinetics; D003213:Conditioning, Psychological / Q000502:physiology; D004558:Electric Stimulation; D004594:Electrophysiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D018684:Glycine Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D016202:N-Methylaspartate / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000502:physiology*; D055095:Optics and Photonics; D010146:Pain / Q000503:physiopathology; D020671:Posterior Horn Cells / Q000187:drug effects / Q000502:physiology*; D011188:Potassium / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013126:Spinal Nerve Roots / Q000166:cytology / Q000502:physiology; D013331:Strychnine / Q000494:pharmacology
D002712:Chlorides; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D018684:Glycine Agents; D009292:Narcotic Antagonists; D009270:Naloxone; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D013331:Strychnine; D011188:Potassium; D001640:Bicuculline