Figure 7.
Peripheral sensitization and presynaptic inhibition alter the amount of postsynaptic inhibition necessary to maintain a normal input-output relationship. (A) Synaptic excitation (syn. exc.) of lamina I neurons is assumed to be a sigmoidal function of the strength of peripheral stimulation (periph. stim.); both are expressed on an arbitrary scale between 0 and 1. Peripheral sensitization steepens that function whereas presynaptic inhibition flattens it. The distinction between modulation of the frequency or amplitude of synaptic inputs is irrelevant for the analysis here. (B) The relationship between fout and synaptic excitation (which is equivalent to the fout-fexc relationship) can be combined with the relationship between synaptic excitation and strength of peripheral stimulation to give the relationship between fout and strength of peripheral stimulation. (C) Peripheral sensitization does not change the relationship between fout and synaptic excitation, but it does change the relationship between fout and strength of peripheral stimulation through its effect illustrated in part A. The resulting horizontal compression (left-pointing arrow) forces the fout-periph. stim. curve for α = 0.5 (dotted curve) into the pink region (center panel). This indicates that sensitization has an effect analogous to disinhibition and, by extension, that the neuron must rely on stronger proportional inhibition (i.e. larger α) to maintain a normal input-output relationship. Conversely, presynaptic inhibition causes a horizontal expansion (right-pointing arrow) that forces the fout-periph. stim. curve outside the pink region (right panel); under these conditions, the neuron could rely weaker proportional inhibition (i.e. smaller α) to maintain a normal input-output relationship. (D) Effects of changing Eanion and α in the context of peripheral sensitization and presynaptic inhibition are illustrated here. The fout/fout0 ratio is calculated for fexc = 80 Hz using fout for the test condition and fout0 for the control condition. Thus, fout/fout0 > 0.6 represents hyperexcitability comparable to that produced by disinhibition, while fout/fout0 > 1 is comparable to hyperexcitability produced by paradoxical excitation. Peripheral sensitization shifts the family of curves leftward (center panel) whereas presynaptic inhibition shifts them rightward (right panel); neither process changes the slopes of those curves, in contrast with the effects of changing α.