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Figure 7 | Molecular Pain

Figure 7

From: Reduction of anion reversal potential subverts the inhibitory control of firing rate in spinal lamina I neurons: towards a biophysical basis for neuropathic pain

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 f out and synaptic excitation (which is equivalent to the f out-f exc relationship) can be combined with the relationship between synaptic excitation and strength of peripheral stimulation to give the relationship between f out and strength of peripheral stimulation. (C) Peripheral sensitization does not change the relationship between f out and synaptic excitation, but it does change the relationship between f out and strength of peripheral stimulation through its effect illustrated in part A. The resulting horizontal compression (left-pointing arrow) forces the f out-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 f out-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 E anion and α in the context of peripheral sensitization and presynaptic inhibition are illustrated here. The f out/f out0 ratio is calculated for f exc = 80 Hz using f out for the test condition and f out0 for the control condition. Thus, f out/f out0 > 0.6 represents hyperexcitability comparable to that produced by disinhibition, while f out/f out0 > 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.

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