Evaluating Mechanisms and Surgical Alternatives to Hyperselective Neurectomy for Treatment of Spasticity in a Rat Model of Spinal Cord Injury.

Abstract

BACKGROUND: Hyperselective neurectomy (HSN) involves transection of most terminal nerve branches supplying a spastic muscle with subsequent recovery of strength resulting from collateral regeneration of spared motor neurons. However, the underlying mechanisms driving spasticity reduction have not been defined. This study aimed to address this knowledge gap and compare the efficacy of HSN to other forms of nerve injury as a therapy for spasticity in a rodent model of spinal cord injury. METHODS: Six weeks after T8 spinal transection, rats ( n = 90) were randomized into 5 groups: sham ( n = 18); HSN of the nerves to gastrocnemius and soleus muscles ( n = 17); transection without repair ( n = 18); transection with repair ( n = 19); and crush ( n = 18) of the tibial nerve. Muscle resistance, modified Ashworth scale, and changes in spindle innervation and VGLUT1 density in the spinal cord were analyzed at 2 and 12 weeks after nerve injury. RESULTS: At 12 weeks, muscle resistance and modified Ashworth scale scores were reduced in transection with repair, but not HSN rats. Reinnervated muscle spindles in both groups presented with atypical morphology. VGLUT1 density representing Ia afferent synapses in the spinal cord was not different between groups. CONCLUSIONS: Nerve transection with primary epineural repair demonstrated enhanced long-term spasticity reduction in spinal cord-injured rats. However, differences in functional synapses on spinal cord motor neurons between groups were not found. Loss of the stretch reflex may alternatively be explained by atypical muscle spindle morphology or central processing in a spinal cord injury cohort. Future studies are needed to further elucidate how peripheral nerve injury modulates disruption of the stretch reflex and treatment of spasticity. CLINICAL RELEVANCE STATEMENT: This novel animal study contributes to our understanding of the mechanisms underlying an emerging surgical treatment for patients with spasticity. This is the first study to investigate the effect of peripheral nerve injury on the stretch reflex in the context of surgical treatment for spasticity. These results provide initial insights into the mechanisms driving the clinically proven treatment benefits of a popular surgical approach for spasticity, and evaluates related surgical strategies that may offer additional benefits.