Functional recovery following peripheral nerve injuries is poor due to muscle atrophy and fibrosis being major contributing factors. Electrical muscle stimulation has been used for decades in some capacity to treat denervation related muscular changes. The research presented in this thesis explores a new stimulation paradigm and its effects on short and long term muscle denervation. The first part of this work describes the new stimulation paradigm and the design and development of the stimulator used to deliver this paradigm. The paradigm involved daily 1-hour stimulation sessions featuring 600 contractions at high stimulus frequencies (100 Hz) and low pulse durations (200 μs). To test the device and paradigm, a pilot study involving muscle stimulation throughout a one month period of denervation in rat lower limb muscles was carried out. The results showed that this short but intense stimulus session significantly reduced the rate of muscle atrophy compared to animals that did not receive stimulation. Furthermore, muscle weight and consequently muscle force were also significantly greater. The stimulus paradigm was then used to investigate muscle that was denervated and immediately repaired. Ideally, immediate nerve repair following nerve injuries produces the best outcome. One month of electrical muscle stimulation following nerve repair enhanced this outcome through significant increases in muscle weight and force. Additionally, contrary to many previous studies, the stimulus paradigm had no negative effects on reinnervation. Taken together, electrical muscle stimulation can provide significant improvements over the best case scenario of immediate nerve repair. The third part of this work investigated the use of chronic electrical muscle stimulation throughout three months of denervation and the impact on reinnervation. Results showed that reinnervation in chronically stimulated animals were no different than animals that were denervated and immediately repaired. The last part of this work combined the use of electrical muscle stimulation with sensory protection in chronically denervated muscle. Sensory protection involves suturing a sensory nerve to protect a muscle during denervation and was shown in previous studies to reduce muscle atrophy, preserve muscle spindles and the structure of the distal nerve stump. The results showed significantly greater muscle weights and force in the combined treatment compared to the individual treatments alone. Reinnervation in these animals was as good as those that were immediately repaired. This suggests that contractile support combined with sensory protection may provide superior functional outcomes in chronically denervated muscle. The findings presented in this thesis provide new evidence for the use of short duration daily electrical muscle stimulation immediately following nerve repair or throughout long term denervation. Evidence for a new therapy, muscle stimulation with sensory protection, is also presented and shown to provide superior functional outcomes compared to either therapy alone. The contributions made in this body of work may provide clinicians with evidence to pursue clinical use of the outlined strategies and ultimately help patients optimally recover from peripheral nerve injuries.

Doctor of Philosophy (PhD)