Contribution of GABA-A receptors to metaplasticity in the spinal dorsal horn.

Metaplasticity is a higher-order form of synaptic plasticity that is induced by synaptic or cellular activity, which by itself may not produce changes in synaptic strength, but which modifies subsequent changes in synaptic efficacy. In this description of metaplasticity in the spinal dorsal horn, we report that a 50 Hz high-frequency tetanus, previously shown to elicit a potentiation of sciatic-evoked A-fiber spinal dorsal horn potentials, caused a depression when coupled with a more rapid rate of repetitive stimulation. This depression appeared to be dependent upon GABA(A) receptor activation because the 50 Hz tetanus elicited a persistent potentiation when the GABA(A) antagonist bicuculline was injected at 1 mg/kg (but not at 0.5 mg/kg) prior to tetanic stimulation. These data suggest the presence of strong inhibitory inputs in the spinal dorsal horn that are activated by an increased rate of primary afferent firing. The activation of these inputs may be necessary to prevent prolonged bursts of afferent activity from modifying synaptic strength because the latter may contribute to the development of persistent pain following peripheral nerve injury.