Plateau potential-dependent windup of the response to primary afferent stimuli in rat dorsal horn neurons

In the spinal cord, repetitive stimulation of nociceptive afferent fibres i nduces a progressive build-up of dorsal horn neuron (DHN) responses. This ' action potential windup' is used as a cellular model of central sensitizati on to pain. It partly relies on synaptic plasticity, being reduced after bl ocking NMDA and neurokinin receptors. Using intracellular recordings in a s lice preparation of the rat spinal cord, we have analysed the implication o f an additional non-synaptic component of windup. Primary afferent fibres w ere electrically stimulated in the dorsal root. Of 47 responding deep DHNs, 17 (36%) produced action potential windup and afterdischarge during consec utive periods of repeated stimuli (0.4-1 Hz) activating high- (n=13 neurons ) and low-threshold (n=6 neurons) afferent fibres. When the NMDA receptors were blocked, the rate of windup did not change. In all neurons, there was an absolute correlation between expression of windup and the production of calcium-dependent plateau potentials. Sensitization of the DHN response, si milar to the synaptically induced windup, was obtained by repetitive intrac ellular injection of depolarizing current pulses. This intracellularly indu ced windup had the same pharmacology as the plateau potential. Synaptically induced windup was also abolished by nifedipine, an L-type calcium-channel blocker. Expression of plateau properties in DHNs is therefore a critical component of windup, operating downstream of synaptic processes. Being asso ciated with calcium influx, generation of plateau potentials could be a lin k between short-term plasticity and the long-term modification of DHN excit ability associated with central sensitization.