Long-term effects of direct current are reproduced by intermittent depolarization of myelinated nerve fibers

Abstract

Direct current (DC) potently increases the excitability of myelinated afferent fibers in the dorsal columns, both during DC polarization of these fibers and during a considerable (>1 h) postpolarization period. The aim of the present study was to investigate whether similarly long-lasting changes in the excitability of myelinated nerve fibers in the dorsal columns may be evoked by field potentials following stimulation of peripheral afferents and by subthreshold epidurally applied current pulses. The experiments were performed in deeply anesthetized rats. The effects were monitored by changes in nerve volleys evoked in epidurally stimulated hindlimb afferents and in the synaptic actions of these afferents. Both were found to be facilitated during as well as following stimulation of a skin nerve and during as well as following epidurally applied current pulses of 5- to 10-ms duration. The facilitation occurring ≤2 min after skin nerve stimulation could be linked to both primary afferent depolarization and large dorsal horn field potentials, whereas the subsequent changes (up to 1 h) were attributable to effects of the field potentials. The findings lead to the conclusion that the modulation of spinal activity evoked by DC does not require long-lasting polarization and that relatively short current pulses and intrinsic field potentials may contribute to plasticity in spinal activity. These results suggest the possibility of enhancing the effects of epidural stimulation in human subjects by combining it with polarizing current pulses and peripheral afferent stimulation and not only with continuous DC. NEW & NOTEWORTHY The aim of this study was to define conditions under which a long-term increase is evoked in the excitability of myelinated nerve fibers. The results demonstrate that a potent and long-lasting increase in the excitability of afferent fibers traversing the dorsal columns may be induced by synaptically evoked intrinsic field as well as by epidurally applied intermittent current pulses. They thus provide a new means for the facilitation of the effects of epidural stimulation.

Ephaptic interactions between myelinated nerve fibres of rodent peripheral nerves

“…At the level of the dorsal roots, the after‐effects were only marginal after 0.5–1 min of the conditioning nerve stimulation (30 or 60 Tib stimuli) but they became statistically significant following the subsequent 2 min period, that is, after 180 Tib stimuli at 1 Hz (Figure a). The increases in nerve volleys evoked by DR stimulation outlasting the conditioning peripheral nerve stimulation were comparable to those outlasting DC administration (Figure c), but both were of shorter duration than the post‐conditioning facilitation of effects of stimulation of the dorsal columns (Figure f) found using the same experimental procedures (Bączyk & Jankowska, ; Kaczmarek & Jankowska, ). We failed, on the other hand, to find post‐conditioning effects of 5 ms current pulses (Figure b) that would replicate effects of such pulses on the excitability of nerve fibres stimulated within the dorsal columns (Figure e).…”

“…(d–f) Increases in the excitability of epidurally stimulated nerve fibres found using similar experimental paradigms (replotted data from figs. 3 and 6 in (Bączyk & Jankowska, ; Kaczmarek & Jankowska, ). (g and h) Maximal increases in the excitability of fibres in the sciatic nerve during and after Tib stimulation (unpublished single series of data from (Bolzoni et al., ) as compared with those during and after DC administration.…”

Transcutaneous spinal direct current stimulation increases corticospinal transmission and enhances voluntary motor output in humans

“…With electrodes placed ventrally and dorsally in direct contact with the spinal cord, dorsal axons (Ia afferents) were demonstrated to be depolarized under a cathode and hyperpolarized under an anode. These findings have now been confirmed in rat experiments in which direct recordings have been made from ascending fibers in the dorsal columns of the spinal cord (Baczyk & Jankowska, 2018;Jankowska, Kaczmarek, Bolzoni, & Hammar, 2017). Importantly, the excitability changes outlast the stimulation and may be seen for several min to hours following relatively brief application of the electrical field (Baczyk & Jankowska, 2018;Kaczmarek, Ristikankare, & Jankowska, 2017).…”

“…In the present study, clear increases in MEP and in ballistic plantar flexion were observed in some participants, whereas in others, only modest or no effects were observed. This is in contrast to animal studies where clear, consistent and reproducible effects are observed (Baczyk & Jankowska, 2018;Jankowska, Kaczmarek, Bolzoni, & Hammar, 2016). There may be several reasons for the larger variability in human participants.…”

Long‐lasting modifications of motoneuron firing properties by trans‐spinal direct current stimulation in rats

“…However, despite the broad application of tsDCS, the physiological mechanisms underlying the observed effects remain unclear, although some significant advances have been made towards our understanding of DC‐evoked neuronal plasticity. Several studies have shown that even brief polarizations can have long‐lasting impacts on spinal circuit excitability, including modified reflexive and locomotor behaviours (Ahmed, ; Murray, Tahayori, & Knikou, ) and altered characteristics of nerve responses that are induced by electrical stimulation (Bączyk & Jankowska, ; Jankowska, Kaczmarek, Bolzoni, & Hammar, ). Although highly important to the field, previous studies have primarily focused on describing the functional effects of direct currents and, therefore, have not indicated which parts of the signal‐generating mechanism are affected by polarization.…”