RATE OF RISE OF THE CUMULATIVE DEPOLARIZATION EVOKED BY REPETITIVE STIMULATION OF SMALL-CALIBER AFFERENTS IS A PREDICTOR OF ACTION-POTENTIAL WINDUP IN RAT SPINAL NEURONS INVITRO

1. The summation of depolarizing postsynaptic potentials (PSPs) evoked by stimulation of primary afferent fibers in lumbar dorsal roots was studied in dorsal and ventral horn neurons in the rat hemisected spina l cord in vitro with current-clamp intracellular recording techniques. PSPs evoked by activation of Adelta and/or C fibers could summate aft er repetitive stimulation at low frequencies: this resulted in a progr essive, long-lasting change in the neuronal membrane potential (V(m)) (cumulative depolarization). Cumulative depolarization was not observe d after stimulation at Abeta-fiber intensity or at frequencies <0.2 Hz . 2. Effective PSP summation resulting in a significant cumulative dep olarization (>5 mV) was observed only if the PSPs evoked were longer t han 4 s. On the other hand, there was no correlation between the ampli tude of cumulative depolarization achieved in a neuron and the absolut e duration of the PSP or the neuronal resting membrane properties (V(m ) and input resistance). 3. With relation to the changes in V(m) durin g the stimulation train, three patterns of response to repetitive stim uli could be detected in both dorsal horn (DH) and ventral horn (VH) n eurons: 1) little or no depolarization throughout the train; 2) an ini tial depolarization, which either remained stationary or decayed to th e resting V(m) after the first 3-4 s of stimulation; or 3) a progressi ve cumulative depolarization increasing throughout the train. 4. Depol arizing the cell by DC current injection resulted in a steeper rise in V(m) in response to repetitive stimuli in one half of VH neurons and in one out of nine DH neurons tested. 5. Action potential windup, an i ncrease in the number of action potentials elicited by each stimulus a s the train progresses, was observed both in DH and in VH cells. C-fib er strength stimulation was the most effective in eliciting windup. Wi ndup was associated with V(m) responses to repetitive stimulation belo nging to the progressive cumulative depolarization pattern. Indeed, cu mulative depolarizations that resulted in windup had significantly ste eper slopes for the V(m) trajectory than those that did not. In those neurons in which DC depolarization by intracellular current injection increased the slope of the V(m) trajectory, DC depolarization could al so bring about action potential windup. 6. These results indicate that , although the generation of longlasting ''slow'' PSPs by high-thresho ld primary afferents is necessary for the summation of synaptic activi ty in the spinal cord at low frequencies, the rate and pattern of the summation does not depend on the absolute duration of the PSPs. Both n etwork-related and postsynaptic, voltage-dependent factors appear to c ontribute to the cumulative depolarization and these, by influencing t he rate of increment, determine whether action potential windup occurs .