Effect of continuous Ia fibre activity suppression on hyperreflexia-related spasticity and maladaptive synaptic connections in the spinal cord after injury.

Abstract

Spasticity is defined as the velocity-dependent hyperexcitability of the stretch reflex that develops after a central nervous system injury. Spasticity is caused by plastic neuronal changes following injury. Current treatments that block spastic muscle contractions do not promote recovery from motor dysfunction. We aimed to confirm that Ia fibre activity suppression, comprising the stretch reflex, reduces spasticity-related hyperreflexia and improves pathological neuronal plastic changes and motor dysfunction. In this study, we created a hemi-transected spinal cord injury mouse model and continued Ia fibre suppression for 2 weeks. The effects of Ia fibre suppression were evaluated electrophysiologically and histologically. In electrophysiology, spasticity-related rate-dependent depression of Hoffman's reflex improved from 0.6 to 0.2 in terms of the rate of amplitude change with reference to 0.1 Hz electrical stimulation. Histologically, the number of synapse buttons of Ia fibres per an α motor neuron reduced from 4.2 to 2.6. However, the α motor neuron activity was still higher than that in the sham mice, possibly due to other residual pathological mechanisms of spasticity. Additionally, motor dysfunction was observed in grid walk and single-reach tasks in vehicle- and drug-administered groups. This study confirmed that continuous Ia fibre suppression partly improved the maladaptive synaptic connections in the spinal cord and relieved spasticity-related hyperreflexia.