Neural signaling in neuropathic pain: A computational modeling perspective

Ma, Xinyue; Khadra, Anmar

doi:10.1016/j.coisb.2024.100509

Cited by 1 publication

(1 citation statement)

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“…Over the past few decades, a range of biophysical models representing different neural subpopulations have been developed, some of which are freely accessible from model databases such as ModelDB ( Hines et al, 2004 ), NeuroML-DB ( Birgiolas et al, 2023 ), and Open Source Brain ( Gleeson et al, 2019 ). Simulations of the current models can describe the patterns of neural firing behavior by the relationship between the firing frequency and the injected current ( Ma and Khadra, 2024 ). For example, Prescott et al (2008) employed the computational models to describe the biophysical basis for three distinct dynamical mechanisms of action potential initiation.…”

Section: Introductionmentioning

confidence: 99%

Computational modeling to study the impact of changes in Nav1.8 sodium channel on neuropathic pain

Kan,

Zhu,

et al. 2024

Front. Comput. Neurosci.

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ObjectiveNav1.8 expression is restricted to sensory neurons; it was hypothesized that aberrant expression and function of this channel at the site of injury contributed to pathological pain. However, the specific contributions of Nav1.8 to neuropathic pain are not as clear as its role in inflammatory pain. The aim of this study is to understand how Nav1.8 present in peripheral sensory neurons regulate neuronal excitability and induce various electrophysiological features on neuropathic pain.MethodsTo study the effect of changes in sodium channel Nav1.8 kinetics, Hodgkin–Huxley type conductance-based models of spiking neurons were constructed using the NEURON v8.2 simulation software. We constructed a single-compartment model of neuronal soma that contained Nav1.8 channels with the ionic mechanisms adapted from some existing small DRG neuron models. We then validated and compared the model with our experimental data from in vivo recordings on soma of small dorsal root ganglion (DRG) sensory neurons in animal models of neuropathic pain (NEP).ResultsWe show that Nav1.8 is an important parameter for the generation and maintenance of abnormal neuronal electrogenesis and hyperexcitability. The typical increased excitability seen is dominated by a left shift in the steady state of activation of this channel and is further modulated by this channel’s maximum conductance and steady state of inactivation. Therefore, modified action potential shape, decreased threshold, and increased repetitive firing of sensory neurons in our neuropathic animal models may be orchestrated by these modulations on Nav1.8.ConclusionComputational modeling is a novel strategy to understand the generation of chronic pain. In this study, we highlight that changes to the channel functions of Nav1.8 within the small DRG neuron may contribute to neuropathic pain.

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