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Interactions between effects of baclofen and cathodal DC on field potentials. Left column, changes in field potentials, evoked by epidural stimulation using the setup outlined in Fig. 1A, following i.v. administration of baclofen. Right column, changes in field potentials, evoked by stimulation of peripheral nerves, using the setup outlined in Fig. 1C, following ionophoretic application of baclofen. A, Changes in the area of the early components of field potentials evoked by epidural stimulation illustrated in Fig. 4 D-F (boxed) in preparations in
Source publication
The aims of the study were to compare effects of baclofen, a GABA B receptor agonist commonly used as an antispastic drug, on direct current (DC) evoked long-lasting changes in the excitability of afferent fibers traversing the dorsal columns and their terminal branches in the spinal cord, and to examine whether baclofen interferes with the develop...
Contexts in source publication
Context 1
... had by itself similar effects on epidurally and peripherally evoked field potentials and reduced these potentials to 70-80% within about 20 min, whether applied intravenously (Fig. 5B) or ionophoretically (Fig. 5 D). However, the effects of the joint application of baclofen and DC differed, depending on whether DC was applied epidurally or intraspinally. Epidurally applied DC facilitated field potentials evoked by epidurally stimulated fibres in the presence of baclofen, i.v., during at least 1 hour of the ...
Context 2
... had by itself similar effects on epidurally and peripherally evoked field potentials and reduced these potentials to 70-80% within about 20 min, whether applied intravenously (Fig. 5B) or ionophoretically (Fig. 5 D). However, the effects of the joint application of baclofen and DC differed, depending on whether DC was applied epidurally or intraspinally. Epidurally applied DC facilitated field potentials evoked by epidurally stimulated fibres in the presence of baclofen, i.v., during at least 1 hour of the post-polarization period (Fig. 5A). In ...
Context 3
... ionophoretically (Fig. 5 D). However, the effects of the joint application of baclofen and DC differed, depending on whether DC was applied epidurally or intraspinally. Epidurally applied DC facilitated field potentials evoked by epidurally stimulated fibres in the presence of baclofen, i.v., during at least 1 hour of the post-polarization period (Fig. 5A). In contrast, when DC was applied intraspinally, in conjunction with ionophoretically or i.v. administered baclofen, it failed to increase field potentials evoked by peripheral nerve ...
Context 4
... occur during the post-polarization period. Instead, they were depressed within 5-15 min following the DC application (Fig. 4 J-L, Fig. 5C). Thereafter, the field potentials gradually returned to control levels even though the depressive effects of baclofen on its own persisted for at least 30 min after the termination of its iontophoresis (Fig. ...
Citations
The review surveys various aspects of the plasticity of nerve fibers, in particular the prolonged increase in their excitability evoked by polarization, focusing on a long-lasting increase in the excitability of myelinated afferent fibers traversing the dorsal columns of the spinal cord. We review the evidence that increased axonal excitability 1) follows epidurally applied direct current (DC) as well as relatively short (5 or 10 ms) current pulses and synaptically evoked intrinsic field potentials; 2) critically depends on the polarization of branching regions of afferent fibers at the sites where they bifurcate and give off axon collaterals entering the spinal gray matter in conjunction with actions of extrasynaptic GABA A membrane receptors; and 3) shares the feature of being activity-independent with the short-lasting effects of polarization of peripheral nerve fibers. A comparison between the polarization evoked sustained increase in the excitability of dorsal column fibers and spinal motoneurons (plateau potentials) indicates the possibility that they are mediated by partly similar membrane channels (including noninactivating type L Cav ⁺⁺ 1.3 but not Na ⁺ channels) and partly different mechanisms. We finally consider under which conditions transspinally applied DC (tsDCS) might reproduce the effects of epidural polarization on dorsal column fibers and the possible advantages of increased excitability of afferent fibers for the rehabilitation of motor and sensory functions after spinal cord injuries.
NEW & NOTEWORTHY This review supplements previous reviews of properties of nerve fibers by surveying recent experimental evidence for their long-term plasticity. It also extends recent descriptions of spinal effects of DC by reviewing effects of polarization of afferent nerve fibers within the dorsal columns, the mechanisms most likely underlying the long-lasting increase in their excitability and possible clinical implications.
The aim of the study was to examine whether the sustained increases in the excitability of afferent fibres traversing the dorsal columns evoked by their polarization depend on the branching points of these fibres. To this end, effects of epidural polarization were compared in four spinal regions in deeply anaesthetized rats; two with the densest collateralization of muscle afferent fibres (above motor nuclei and Clarke's column) and two where the collateralization is more sparse (rostral and caudal to motor nuclei respectively. The degree of collateralization in different segments was reconstructed in retrogradely labelled afferent fibres in the rat. Nerve volleys evoked in peripheral nerves by electrical stimulation of the dorsal columns within these regions were used as a measure of the excitability of the stimulated fibres. Potent increases in the excitability were evoked by polarization above motor nuclei and Clarke's column, both during constant direct current (DC) polarization (1 µA for 1 min) and for at least 30 min following DC polarization. Smaller excitability increases occurred during the polarization within other regions and were thereafter either absent or rapidly declined after its termination. The post-polarization increases in excitability were counteracted by the GABA A receptor antagonist, bicuculline and the α5 GABA A extrasynaptic receptor antagonist L655708 and enhanced by the GABA A receptor agonist muscimol and by ionophoretically applied GABA. As extrasynaptic α5 GABA A receptors have been found close to Na-channels within branching points, these results are consistent with the involvement of branching points in the induction of the sustained post-polarization increases in fibre excitability.
