TY - JOUR
T1 - Subthreshold oscillations facilitate neuropathic spike discharge by overcoming membrane accommodation
AU - Kovalsky, Yifat
AU - Amir, Ron
AU - Devor, Marshall
PY - 2008/3
Y1 - 2008/3
N2 - We have used computer simulation to better understand how the prolonged époques of repetitive discharge that underlie chronic neuropathic pain are generated. When subjected to step depolarization the cell soma of most primary afferents produces a single spike, or a brief spike burst, and then falls silent. Slow ramp depolarization typical of physiological stimuli does not evoke any spikes, due to the pronounced membrane accommodation of these neurons. Prior work in live DRG neurons suggests that prolonged neuropathic discharge occurs in neurons that generate subthreshold membrane potential oscillations; the rising (depolarizing) phase of the oscillation sinusoid triggers discharge that can last indefinitely. The specific contribution of oscillations to prolonged electrogenesis is not fully understood, however, as they typically add no more than ∼ 5 mV to overall cell depolarization. We constructed a computer simulation of a dorsal root ganglion neuron that generates subthreshold oscillations and prolonged electrogenesis. We found that the slope of the rising phase of the oscillation sinusoid, in addition to its amplitude, is an important factor in the ability of oscillations to generate spike trains. The relatively steep slope of oscillation sinusoids facilitates electrogenesis by transiently overcoming the membrane accommodation associated with physiological slow ramp depolarization.
AB - We have used computer simulation to better understand how the prolonged époques of repetitive discharge that underlie chronic neuropathic pain are generated. When subjected to step depolarization the cell soma of most primary afferents produces a single spike, or a brief spike burst, and then falls silent. Slow ramp depolarization typical of physiological stimuli does not evoke any spikes, due to the pronounced membrane accommodation of these neurons. Prior work in live DRG neurons suggests that prolonged neuropathic discharge occurs in neurons that generate subthreshold membrane potential oscillations; the rising (depolarizing) phase of the oscillation sinusoid triggers discharge that can last indefinitely. The specific contribution of oscillations to prolonged electrogenesis is not fully understood, however, as they typically add no more than ∼ 5 mV to overall cell depolarization. We constructed a computer simulation of a dorsal root ganglion neuron that generates subthreshold oscillations and prolonged electrogenesis. We found that the slope of the rising phase of the oscillation sinusoid, in addition to its amplitude, is an important factor in the ability of oscillations to generate spike trains. The relatively steep slope of oscillation sinusoids facilitates electrogenesis by transiently overcoming the membrane accommodation associated with physiological slow ramp depolarization.
KW - Accommodation
KW - Ectopic firing
KW - Neuropathic pain
KW - Repetitive firing
KW - Subthreshold oscillations
UR - http://www.scopus.com/inward/record.url?scp=39249083820&partnerID=8YFLogxK
U2 - 10.1016/j.expneurol.2007.10.018
DO - 10.1016/j.expneurol.2007.10.018
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C2 - 18162184
AN - SCOPUS:39249083820
SN - 0014-4886
VL - 210
SP - 194
EP - 206
JO - Experimental Neurology
JF - Experimental Neurology
IS - 1
ER -