Effects of direct current (DC) on nerve fibers have primarily been investigated during or just after DC application. However, locally applied cathodal DC was recently demonstrated to increase the excitability of intraspinal preterminal axonal branches for >1 h. The aim of this study was therefore to investigate whether DC evokes a similarly long-lasting increase in the excitability of myelinated axons within the dorsal columns. The excitability of dorsal column fibers stimulated epidurally was monitored by recording compound action potentials in peripheral nerves in acute experiments in deeply anesthetized rats. The results show that ) cathodal polarization (0.8-1.0 µA) results in a severalfold increase in the number of epidurally activated fibers and) the increase in the excitability appears within seconds, ) lasts for>1 h, and ) is activity independent, as it does not require fiber stimulation during the polarization. These features demonstrate an unexplored form of plasticity of myelinated fibers and indicate the conditions under which it develops. They also suggest that therapeutic effects of epidural stimulation may be significantly enhanced if it is combined with DC polarization. In particular, by using DC to increase the number of fibers activated by low-intensity epidural stimuli, the low clinical tolerance to higher stimulus intensities might be overcome. The activity independence of long-lasting DC effects would also allow the use of only brief periods of DC polarization preceding epidural stimulation to increase the effect. The study indicates a new form of plasticity of myelinated fibers. The differences in time course of DC-evoked increases in the excitability of myelinated nerve fibers in the dorsal columns and in preterminal axonal branches suggest that distinct mechanisms are involved in them. The results show that combining epidural stimulation and transspinal DC polarization may dramatically improve their outcome and result in more effective pain control and the return of impaired motor functions.

The effects of trans-spinal direct current (DC) stimulation (tsDCS) on specific neuronal populations are difficult to elucidate, as it affects a variety of neuronal networks. However, facilitatory and depressive effects on neurons processing information from the skin and from muscles can be evaluated separately when weak (0.2-0.3 μA) DC is applied within restricted areas of the rat spinal cord. The effects of such local DC application were recently demonstrated to persist for at least 1 h, and to include changes in the excitability of afferent fibres and their synaptic actions. However, whether these effects require activation of afferent fibres in spinal neuronal pathways during DC application, i.e. whether they are activity-dependent or activity-independent, remained an open question. The aim of the present study was to address this question by analysing the effects of local DC application on monosynaptic actions of muscle and skin afferents (extracellular field potentials) and afferent fibre excitability. The results revealed that long-lasting post-polarization changes evoked without concomitant activation of afferent fibres replicate changes evoked by stimuli applied during, before and after polarization. The study leads to the conclusion that the reported effects are activity-independent. As this conclusion applies to the local effects of DC application in at least two spinal pathways and to the effects of both cathodal and anodal polarization, it indicates that some of the more widespread effects of trans-spinal and trans-cranial stimulation (both tsDCS and transcranial DC stimulation) may be activity-independent. The results may therefore contribute to the design of more specific DC applications in clinical practice.

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Direct current (DC) polarization has been demonstrated to alleviate the effects of various deficits in the operation of the central nervous system. However, the effects of trans-spinal DC stimulation (tsDCS) have been investigated less extensively than the effects of transcranial DC stimulation, and their cellular mechanisms have not been elucidated. The main objectives of this study were, therefore, to extend our previous analysis of DC effects on the excitability of primary afferents and synaptic transmission by examining the effects of DC on two spinal modulatory feedback systems, presynaptic inhibition and post-activation depression, in an anaesthetized rat preparation. Other objectives were to compare the effects of locally and trans-spinally applied DC (locDC and tsDCS). Local polarization at the sites of terminal branching of afferent fibres was found to induce polarity-dependent actions on presynaptic inhibition and post-activation depression, as cathodal locDC enhanced them and anodal locDC depressed them. In contrast, tsDCS modulated presynaptic inhibition and post-activation depression in a polarity-independent fashion because both cathodal and anodal tsDCS facilitated them. The results show that the local presynaptic actions of DC might counteract both excessively strong and excessively weak monosynaptic actions of group Ia and cutaneous afferents. However, they indicate that trans-spinally applied DC might counteract the exaggerated spinal reflexes but have an adverse effect on pathologically weakened spinal activity by additional presynaptic weakening. The results are also relevant for the analysis of the basic properties of presynaptic inhibition and post-activation depression because they indicate that some common DC-sensitive mechanisms contribute to them.

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