Riluzole decreases flexion withdrawal reflex but not voluntary ankle torque in human chronic spinal cord injury.

The objectives of this study were to probe the contribution of spinal neuron persistent sodium conductances to reflex hyperexcitability in human chronic spinal cord injury. The intrinsic excitability of spinal neurons provides a novel target for medical intervention. Studies in animal models have shown that persistent inward currents, such as persistent sodium currents, profoundly influence neuronal excitability, and recovery of persistent inward currents in spinal neurons of animals with spinal cord injury routinely coincides with the appearance of spastic reflexes. Pharmacologically, this neuronal excitability can be decreased by agents that reduce persistent inward currents, such as the selective persistent sodium current inhibitor riluzole. We were able to recruit seven subjects with chronic incomplete spinal cord injury who were not concurrently taking antispasticity medications into the study. Reflex responses (flexion withdrawal and H-reflexes) and volitional strength (isometric maximum voluntary contractions) were tested at the ankle before and after placebo-controlled, double-blinded oral administration of riluzole (50 mg). Riluzole significantly decreased the peak ankle dorsiflexion torque component of the flexion withdrawal reflex. Peak maximum voluntary torque in both dorsiflexion and plantarflexion directions was not significantly changed. Average dorsiflexion torque sustained during the 5-s isometric maximum voluntary contraction, however, increased significantly. There was no effect, however, on the monosynaptic plantar and dorsiflexor H-reflex responses. Overall, these results demonstrate a contribution of persistent sodium conductances to polysynaptic reflex excitability in human chronic spinal cord injury without a significant role in maximum strength production. These results suggest that intrinsic spinal cellular excitability could be a target for managing chronic spinal cord injury hyperreflexia impairments without causing a significant loss in volitional strength.

Persistent inward currents in rat ventral horn neurones.

Throughout the mammalian spinal cord, interneurones have been shown to exhibit distinct firing patterns in response to a step of injected current. In this study of ventral horn interneurones in a thick slice preparation of the lumbar cord of 11-19-day-old-rats, four distinct firing patterns were observed and classified as repetitive-firing, repetitive/burst, initial-burst or single-spiking. The hypothesis that a persistent sodium current was the predominant determinant of cell firing behaviour was investigated. A slow voltage ramp was used to assess persistent inward currents (PICs). Cells with repetitive-firing patterns had significantly larger PICs than cells displaying repetitive/burst, initial-burst or single-spiking patterns. Repetitive-firing, repetitive/burst and initial-burst-firing cells were reduced to a single-spiking pattern with the application of riluzole, which also markedly reduced the persistent sodium current. Persistent sodium current was found to account for most of the PIC with only a small contribution from L-type calcium current. These results suggest that the persistent sodium current plays a major role in determining firing patterns in these cells.