Modulation of motoneuronal firing behavior after spinal cord injury using intraspinal microstimulation current pulses: a modeling study

Elbasiouny, Sherif M.; Mushahwar, Vivian K.

doi:10.1152/japplphysiol.01222.2006

Cited by 23 publications

(17 citation statements)

References 55 publications

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“…A third theory focuses on the inactivation of sodium channel as the mechanism of KHFAC block [3,29,33,34]. Computation modeling studies indicated that KHFAC resulted in an increased inward sodium current, leading to a dynamic depolarization of many nodes under the electrode [33,35].…”

Section: Electrical Nerve Block Using Khfacmentioning

confidence: 99%

Reversible Conduction Block in Peripheral Nerve Using Electrical Waveforms

et al. 2017

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Introduction Electrical nerve block uses electrical waveforms to block action potential propagation. Materials & Methods Two key features that distinguish electrical nerve block from other nonelectrical means of nerve block: block occurs instantly, typically within 1 s; and block is fully and rapidly reversible (within seconds). Results Approaches for achieving electrical nerve block are reviewed, including kilohertz frequency alternating current and charge-balanced polarizing current. We conclude with a discussion of the future directions of electrical nerve block. Conclusion Electrical nerve block is an emerging technique that has many significant advantages over other methods of nerve block. This field is still in its infancy, but a significant expansion in the clinical application of this technique is expected in the coming years.

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Section: Electrical Nerve Block Using Khfacmentioning

confidence: 99%

Reversible Conduction Block in Peripheral Nerve Using Electrical Waveforms

et al. 2017

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“…The former pulses deactivate the Na + channels at the first node of Ranvier and reduce axonal conduction, whereas the latter pulses inactivate the Na + channels at the first node of Ranvier and block axonal conduction. These pulses are effective even in the presence of increased sprouting and changes in motoneuronal intrinsic properties encountered after long-term SCI 80. The proposed pulses could provide a means for reducing spasticity without prohibiting muscle activation through residual volitional drive.…”

Section: Current Treatments Of Spasticitymentioning

confidence: 99%

Management of Spasticity After Spinal Cord Injury: Current Techniques and Future Directions

Elbasiouny

Moroz

Bakr³

et al. 2009

Neurorehabil Neural Repair

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186

125

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Spasticity, resulting in involuntary and sustained contractions of muscles, may evolve in patients with stroke, cerebral palsy, multiple sclerosis, brain injury, and spinal cord injury (SCI). The authors critically review the neural mechanisms that may contribute to spasticity after SCI and assess their likely degree of involvement and relative significance to its pathophysiology. Experimental data from patients and animal models of spasticity as well as computer simulations are evaluated. The current clinical methods used for the management of spasticity and the pharmacological actions of drugs are discussed in relation to their effects on spinal mechanisms. Critical assessment of experimental findings indicates that increased excitability of both motoneurons and interneurons plays a crucial role in pathophysiology of spasticity. New interventions, including forms of spinal electrical stimulation to suppress increased neuronal excitability, may reduce the severity of spasticity and its complications.

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“…There are two modern hypotheses. Several recent simulation studies have noted a correlation between sodium channel inactivation and HFB, hypothesizing that the likely mechanism for conduction block is a sodium channel inactivation induced by membrane depolarization [1, 21, 25, 35]. A nodal recording study in the frog by Bromm describes axonal depolarization during HFS, supporting this hypothesis, although he did not explicitly address the mechanisms of the conduction blocking phenomenon (see Figure 1, reprint from Bromm 1975) [32].…”

Section: Introductionmentioning

confidence: 99%

Dynamics and sensitivity analysis of high-frequency conduction block

Ackermann¹,

Bhadra²,

Gerges³

et al. 2011

J. Neural Eng.

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The local delivery of extracellular high frequency stimulation (HFS) has been shown to be a fast acting and quickly reversible method of blocking neural conduction, and is currently being pursued for several clinical indications. However, the mechanism for this type of nerve block remains unclear. In this study, we investigate two hypotheses: 1) That depolarizing currents promote conduction block via inactivation of sodium channels, and 2) that the gating dynamics of the fast sodium channel are the primary determinate of minimal blocking frequency. Hypothesis 1 was investigated using a combined modeling and experimental study to investigate the effect of depolarizing and hyperpolarizing currents on high frequency block. The results of the modeling study show that both depolarizing and hyperpolarizing currents play an important role in conduction block and that the conductance to each of three ionic currents increases relative to resting values during HFS. However, depolarizing currents were found to promote the blocking effect, and hyperpolarizing currents were found to diminish the blocking effect. Inward sodium currents were larger than the sum of the outward currents, resulting in a net depolarization of the nodal membrane. Our experimental results support these findings and closely match results from the equivalent modeling scenario: intra-peritoneal administration of the persistent sodium channel blocker ranolazine resulted in an increase in the amplitude of HFS required to produce conduction block in rats, confirming that depolarizing currents promote the conduction block phenomenon. Hypothesis 2 was investigated using a spectral analysis of the channel gating variables in a single fiber axon model. The results of this study suggested a relationship between the dynamical properties of specific ion channel gating elements and the contributions of corresponding conductances to block onset. Specifically, we show that the dynamics of the fast sodium inactivation gate are too slow to track the high frequency changes in membrane potential during HFS, and that the behavior of the fast sodium current was dominated by the low frequency depolarization of the membrane. As a result, in the blocked state, only 5.4% of nodal sodium channels were found to be in the activatable state in the node closest to the blocking electrode, resulting in a conduction block. Moreover, we find that the corner frequency for the persistent sodium channel activation gate corresponds to the frequency below which high frequency stimuli of arbitrary amplitude are incapable of inducing conduction block.

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Modulation of motoneuronal firing behavior after spinal cord injury using intraspinal microstimulation current pulses: a modeling study

Cited by 23 publications

References 55 publications

Reversible Conduction Block in Peripheral Nerve Using Electrical Waveforms

Reversible Conduction Block in Peripheral Nerve Using Electrical Waveforms

Management of Spasticity After Spinal Cord Injury: Current Techniques and Future Directions

Dynamics and sensitivity analysis of high-frequency conduction block

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