Date on Master's Thesis/Doctoral Dissertation

8-2017

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Physiology and Biophysics

Degree Program

Physiology and Biophysics, PhD

Committee Chair

Magnuson, David

Committee Co-Chair (if applicable)

Petruska, Jeffrey

Committee Member

Petruska, Jeffrey

Committee Member

Howland, Dena

Committee Member

Hoying, James

Committee Member

Lominadze, David

Committee Member

Schuschke, Dale

Author's Keywords

spinal cord injury; rehabilitation; stretching; locomotor function; nociceptive afferents

Abstract

Spinal cord injury (SCI) is the second leading cause of paralysis in the United States, affecting around 282,000 people with 17,000 new cases each year. Initial and secondary damage to the spinal cord disrupts multiple descending pathways that modulate the function of sympathetic preganglionic neurons and central pattern generating circuitry. Resulting loss of autonomic and locomotor functions, as well as decreased levels of physical activity, lead to a myriad of complications that affect multiple organ systems and significantly reduce both quality of life and life expectancy in individuals with SCI. Spasticity and muscle contractures are two common secondary conditions that develop in the chronic stages of SCI as a result of neurobiological and soft tissue adaptations. Stretching is the widely accepted initial therapy for the treatment of both spasticity and muscle contractures. Unlike humans, rats with experimental incomplete SCI have robust locomotor recovery and do not develop significant muscle contractures or spasticity. One of the long-standing operating principles in the Magnuson laboratory is that rats retrain or rehabilitate themselves through large amounts of in-cage activity. A previous graduate student in our lab, Krista Caudle, tested this hypothesis using custom designed wheelchairs to immobilize Sprague Dawley rats with mild-moderate SCIs. As expected, the immobilized SCI animals did not recover their locomotor function and, in addition, developed muscle contractures. To mimic the approach used in the clinic for the treatment of contractures, a hindlimb stretching protocol was developed and implemented as part of our daily care routine. As a control, non-immobilized SCI rats also received stretching therapy. Surprisingly, stretched rats and wheelchair immobilized rats showed similar impairments in locomotor recovery. This finding was alarming and warranted further studies. The work presented in this thesis is a continuation of the stretching projects in the Magnuson laboratory. Four major studies were carried out in order to improve our understanding of this stretching phenomenon and to begin uncovering the underlying physiological mechanisms. The following experiments revealed that hindlimb stretching disrupts locomotor function in rats with acute and chronic moderately-severe SCI. We also determined that dynamic “range of motion” stretching resulted in a similar pattern of locomotor impairment as our standard static stretch-and-hold protocol in rats with moderate sub-acute SCIs. Furthermore, using kinematics and electromyography (EMG), we determined that one of the most frequent responses to stretch in the rat hindlimbs is similar to human clonus. The significance of these findings are three-fold. First, to our knowledge, there has not been a specific description of clonus in the rat model of the SCI previously. Second, the similarity of the responses to stretch between rats and humans make a compelling argument for the clinical relevance of the stretching phenomenon. Finally, we determined that stretch-induced locomotor deficits depend on the presence of nociceptive afferents. Speculations about the specific physiological mechanisms of the stretching phenomenon and future directions are discussed. Comprehensive review of the stretching literature revealed a major problem in the rationale that is frequently provided for the use of stretching in the management of muscle contractures after SCI. In light of this work, a perspective on the future of stretching therapy in the rehabilitation after SCI is provided.

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