Long-lasting increase in axonal excitability following epidurally applied DC

Effects of direct current (DC) on nerve fibres 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 more than one hour. 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 fibres stimulated epidurally was monitored by recording compound action potentials in peripheral nerves in acute experiments in deeply anaesthetized rats. The results show that (i) cathodal polarization (0.8-1.0 µA) results in a several-fold increase in the number of epidurally activated fibres, (ii) the increase in the excitability appears within seconds, (iii) lasts for more than an hour and (iv) is activity-independent as it does not require fibre stimulation during the polarization. These features demonstrate an unexplored form of plasticity of myelinated fibres 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 fibres 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 using only brief periods of DC polarization preceding epidural stimulation to increase the effect.

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