Effects of Anesthesia and Potential Antispastic Agents in an Experimental Model of Spasticity.

Spasticity is a common motor disorder in spinal cord injured-patients. Therapeutic agents used to treat the motor abnormalities exist but are often unsatisfactory. Tests of potential pharmacotherapies are routinely conducted in anesthetized intact or acutely spinal animals, conditions which do not accurately simulate the human situation. The purpose of this dissertation was to develop, validate and use the chronic spinal rat as a model of spasticity that closely approximates the human spastic syndrome to evaluate antispastic agents. The main goals of this research project were to: (1) demonstrate the development of spasticity in the chronic spinal rat; (2) determine effects of anesthesia on spinal reflex measurement; and (3) evaluate two proposed antispastics. These objectives were accomplished by quantifying three parameters of the monosynaptic H-reflex: threshold, magnitude and rate-sensitive depression. H-reflexes were elicited by tibial nerve stimulation at three different frequencies and recorded from ipsilateral hindpaw plantar muscles in intact and 28- and 60-day spinal rats. Spasticity was defined subsequent to spinalization as decreased H-reflex thresholds (increased sensitivity), increased magnitudes (hyperreflexia) and decreased rate-sensitive depression (reduced response inhibition), relative to intact measurements.