ABSTRACT

It is well known that persistent changes in conduction velocity occur after nerve fiber regeneration, and the mechanism for this abnormality has been ascribed to a deficit in caliber. It is, however, not known whether regenerating peripheral axons show persistent alterations in the resting membrane potential or the ability to compensate for physiological variations in membrane potential. Threshold tracking is a clinically available electrophysiological method that can provide clues about the membrane potential of peripheral axons in vivo by measuring changes in excitability (the ease of action potential triggering). We developed a cat model to investigate longitudinally the recovery in excitability of peripheral motor axons after tibial nerve crush. To study recovery we extended our investigations for up to five years after the lesion. The experimental work was carried out in the Panum Institute, University of Copenhagen.

We found that regenerated nerves show persistent abnormalities consistent with membrane hyperpolarization. Furthermore, the recovery in excitability during reperfusion after ischaemia and after repetitive stimulation was prolonged in regenerated nerves, and the temperature dependence of excitability was increased. These data indicate that the demand for Na + /K + pumping may be increased in regenerated nerves and this may explain the observed membrane hyperpolarization.

The clinical relevance of our findings was ascertained by comparing the excitability data obtained from cat to excitability of normal and regenerated human motor nerves. The human investigations were carried out at Rigshospitalet, Copenhagen. It is likely that persistent hyperpolarization may also have negative consequences on activity and energy demand of regenerated human nerves.