Effect of High-Frequency Alternating Current on Spinal Afferent Nociceptive Transmission

Department of Orthopaedic Surgery, NYU Hospital for Joint Diseases, New York, NY, USA.
Neuromodulation (Impact Factor: 2.7). 12/2012; 16(4). DOI: 10.1111/ner.12015
Source: PubMed


The study was performed to test the hypothesis that high-frequency alternating current (HFAC) ranging from 2 to 100 kHz delivered to the spinal dorsal roots reduces activity of spinal wide dynamic range (WDR) dorsal horn neurons (DHNs) during noxious peripheral stimulation.

Materials and methods:
This hypothesis was tested in both small and large animal in vivo preparations. Single-unit extracellular spinal DHN recordings were performed in seven adult rats and four adult goats while testing various parameters of HFAC delivered to the nerve roots or dorsal root entry zone using various electrode types. Frequencies tested ranged from 2 to 100 kHz but focused on the 3 to 50 kHz range. This study investigated the ability of HFAC to inhibit WDR neuronal activity evoked by noxious mechanical (pinch), and electrical stimuli was tested but was primarily focused on electrical stimulation.

Rat Study: Effects of HFAC were successfully tested on 11 WDR neurons. Suppression or complete blockade of evoked activity was observed in all 11 of these neurons. Complete data sets for neurons systematically tested with 15 baseline and post-HFAC stimulus sweeps were obtained in five neurons, the nociceptive activity of which was suppressed by an average of 69 ± 9.7% (p < 0.0001). Goat Study: HFAC was successfully tested on 15 WDR neurons. Conclusive suppression or complete nociceptive blockade was observed for 12/15 and complete data sets with at least 20 baseline and post-HFAC stimulus sweeps were obtained from eight DHNs. For these neurons the mean activity suppression was 70 ± 10% (p < 0.005).

Delivery of HFAC to the region of epidural nerve root or nerve root entry inhibited afferent nociceptive input and therefore may have potential to serve as an alternative to traditional spinal cord stimulation without sensory paresthesia as neuronal activation cannot occur at frequencies in this range.

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    • "Margin requirements for the other pages Paper size this page US Letter Figure 2: Strength-duration surface for current threshold selection to generate action potential with HH model. nociceptive input [7], possibly via axonal conduction block. "
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    ABSTRACT: Abstract—The Hodgkin-Huxley model describes the dynamics of action potentials and the resultant currents that pass through voltage-dependent ion channels in the neuronal membrane. Another type of ion channels, transmitter-activated ion channels primarily expressed on dendrites, are involved in synaptic transmission from presynaptic neurons. Along these cable-like dendrites, the effect of spatial potential gradients can be mimicked by appropriate transmembrane current density injections, producing summated postsynaptic membrane potential alterations at the axon hillock of the soma. Alterations of membrane potentials at the axon hillock will open or close the voltage-dependent ion channels, where the kinetics as well as the activation/deactivation properties of the ion channels will determine the neuronal response. To explore this phenomenon, the sensitivity of lumped membrane potentials to current pulse perturbation (i.e., excitability) was explored at a population level where the Hodgkin-Huxley (HH) type axonal neural mass model (specifically, axon hillock) was driven by subthreshold sinusoidal transmembrane current injections from a somatodendritic synaptic mass model. Although knowledge about both, ion channel distributions and their response properties is necessary to delineate and parameterize a realistic lumped mass compartment model, we investigated a simplified HH model to primarily evaluate our dynamical systems analysis approach. Specifically, the lumped membrane potential of the axonal neural mass model was found to settle to one of two possible stable states based on the stimulation frequency during the subthreshold alternating current (AC) stimulation via the synaptic mass model. These altered stable states of the axonal neural mass model were explored for excitability using current perturbations via the synaptic mass model. One of the states (activated potassium depolarization blockade) was found to be less excitable than the other (inactivated sodium refractory blockade). It is interesting to note that even with such a simplified HH model, two mechanisms -activated potassium depolarization blockade and inactivated sodium refractory blockade -were detected, and we concluded that at a population level, the propensity to neuronal response may be reduced under AC stimulation via different mechanisms where high (~kHz) frequencies may provide another neuromodulation tool.
    2013 6th International IEEE/EMBS Conference on Neural Engineering (NER); 11/2013

  • Neuromodulation 07/2013; 16(4):285-91. DOI:10.1111/ner.12103 · 2.70 Impact Factor
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    ABSTRACT: Spinal cord stimulation (SCS) is a useful neuromodulatory technique for treatment of certain neuropathic pain conditions. However, the optimal stimulation parameters remain unclear. In rats after L5 spinal nerve ligation, the authors compared the inhibitory effects on mechanical hypersensitivity from bipolar SCS of different intensities (20, 40, and 80% motor threshold) and frequencies (50, 1 kHz, and 10 kHz). The authors then compared the effects of 1 and 50 Hz dorsal column stimulation at high- and low-stimulus intensities on conduction properties of afferent Aα/β-fibers and spinal wide-dynamic-range neuronal excitability. Three consecutive daily SCS at different frequencies progressively inhibited mechanical hypersensitivity in an intensity-dependent manner. At 80% motor threshold, the ipsilateral paw withdrawal threshold (% preinjury) increased significantly from pre-SCS measures, beginning with the first day of SCS at the frequencies of 1 kHz (50.2 ± 5.7% from 23.9 ± 2.6%, n = 19, mean ± SEM) and 10 kHz (50.8 ± 4.4% from 27.9 ± 2.3%, n = 17), whereas it was significantly increased beginning on the second day in the 50 Hz group (38.9 ± 4.6% from 23.8 ± 2.1%, n = 17). At high intensity, both 1 and 50 Hz dorsal column stimulation reduced Aα/β-compound action potential size recorded at the sciatic nerve, but only 1 kHz stimulation was partially effective at the lower intensity. The number of actions potentials in C-fiber component of wide-dynamic-range neuronal response to windup-inducing stimulation was significantly decreased after 50 Hz (147.4 ± 23.6 from 228.1 ± 39.0, n = 13), but not 1 kHz (n = 15), dorsal column stimulation. Kilohertz SCS attenuated mechanical hypersensitivity in a time course and amplitude that differed from conventional 50 Hz SCS, and may involve different peripheral and spinal segmental mechanisms.
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