Modelling activity-dependent changes of velocity in C-fibers

Modelling activity-dependent changes of velocity in C-fibers AbstractAimsWhen C-nociceptors are activated repeatedly using electrical stimulation at relatively low frequencies (0.125–2 Hz), their propagation velocity will decrease. This is referred to as activity-dependent slowing (ADS). The main reason why activity-dependent changes in velocity are of interest is that they can be recorded directly, using invasive methods (microneurography), in patients with chronic pain. Interestingly, in certain patients with neuropathic pain, reduced activity-dependent slowing of conduction has been observed, indicating that these axons have an increased excitability. Through a computational model, it is possible to link such velocity alterations with changes in active conductances, opening for an understanding the underlying excitability changes occurring in these patients.MethodsWe have developed a detailed multicompartment model of a C-nociceptor fiber. This model incorporates a wide range of voltage-gated ion channels (Nav1.7, Nav1.8, Nav1.9, Kdr, KA, KM, KNa and h) which were implemented across a detailed and realistic axon morphology.ResultsThe model predicts that the small diameter of the axon can accumulate intracellular sodium when it is repeatedly activated in a similar fashion as during single fiber microneurography. This increase of intracellular sodium concentration can shift the balance between ion channel currents, shift the membrane potential and membrane input resistance, and thereby generate activity-dependent changes of velocity, such as ADS as well as recovery cycle supernormality.ConclusionsOur results thus provide insight into how activity-dependent excitability changes can be generated in C-fibers. By identifying which ion channels are contributing to activity-dependent changes of velocity this could provide insight into ion channel alterations in neuropathic pain patients. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Scandinavian Journal of Pain de Gruyter

Modelling activity-dependent changes of velocity in C-fibers

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Publisher
De Gruyter
Copyright
© 2017 Scandinavian Association for the Study of Pain
ISSN
1877-8860
eISSN
1877-8879
D.O.I.
10.1016/j.sjpain.2017.04.062
Publisher site
See Article on Publisher Site

Abstract

AbstractAimsWhen C-nociceptors are activated repeatedly using electrical stimulation at relatively low frequencies (0.125–2 Hz), their propagation velocity will decrease. This is referred to as activity-dependent slowing (ADS). The main reason why activity-dependent changes in velocity are of interest is that they can be recorded directly, using invasive methods (microneurography), in patients with chronic pain. Interestingly, in certain patients with neuropathic pain, reduced activity-dependent slowing of conduction has been observed, indicating that these axons have an increased excitability. Through a computational model, it is possible to link such velocity alterations with changes in active conductances, opening for an understanding the underlying excitability changes occurring in these patients.MethodsWe have developed a detailed multicompartment model of a C-nociceptor fiber. This model incorporates a wide range of voltage-gated ion channels (Nav1.7, Nav1.8, Nav1.9, Kdr, KA, KM, KNa and h) which were implemented across a detailed and realistic axon morphology.ResultsThe model predicts that the small diameter of the axon can accumulate intracellular sodium when it is repeatedly activated in a similar fashion as during single fiber microneurography. This increase of intracellular sodium concentration can shift the balance between ion channel currents, shift the membrane potential and membrane input resistance, and thereby generate activity-dependent changes of velocity, such as ADS as well as recovery cycle supernormality.ConclusionsOur results thus provide insight into how activity-dependent excitability changes can be generated in C-fibers. By identifying which ion channels are contributing to activity-dependent changes of velocity this could provide insight into ion channel alterations in neuropathic pain patients.

Journal

Scandinavian Journal of Painde Gruyter

Published: Jul 1, 2017

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