Dissertation
The role of mechanosensitive, IB4-positive nociceptive afferent input in forelimb motor function and rehabilitation after spinal cord injury
Doctor of Philosophy (Ph.D.), Drexel University
May 2024
DOI:
https://doi.org/10.17918/00001937
Abstract
Cervical spinal cord injury (SCI) results in alterations in sensory input and motor output. These losses significantly reduce an individual's independence and quality of life. The highest priority for individuals living with SCI is regaining control and use of their arm and hand. Unfortunately, the current standard of care, physical rehabilitation, provides only minimal recovery, and promising technologies harnessing electrical stimulation, driving regeneration, and replicating motor outputs through brain-machine interfaces are still in their nascent stages. Therefore, it is of vital importance to understand the mechanistic underpinnings of rehabilitative paradigms with particular focus on alterations within neural circuits involved in sensorimotor processing so that therapies can be enhanced to improve outcomes. This dissertation focuses on the influence of aberrant nociceptive input to the spinal cord on reach-to-grasp function under normal conditions, following spinal cord injury, and during rehabilitation. Sprague-Dawley rats were given a C5 unilateral contusion on their dominant side and underwent rehabilitative strength training protocols at post-injury timepoints consistent with human treatment for SCI. Strength training after SCI improved pull force but failed to improve fine motor pellet retrieval tasks. The role of the mechanically sensitive nociceptor was tested by microinjecting a cytotoxin specifically targeted to IB4+ cells into the C7 and C8 dorsal root ganglia. More injured rats with ablated nociceptors were able to grasp food pellets compared to injured rats with intact nociceptors. When combined, mechanosensitive nociceptor ablation did not improve the efficacy of strength training after SCI. Thus, the limited effectiveness of strength training to improve reaching and grasping was determined to be independent of mechanosensitive nociceptor activity. The evidence that altered mechanosensitive nociceptor input after SCI is detrimental to the recovery of grasping provides a novel therapeutic target for motor control.
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Details
- Title
- The role of mechanosensitive, IB4-positive nociceptive afferent input in forelimb motor function and rehabilitation after spinal cord injury
- Creators
- John Robert Walker
- Contributors
- Megan R. Detloff (Advisor)Kimberly J. Dougherty (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- ix, 187 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- College of Medicine; Neurology; Drexel University
- Other Identifier
- 991021867712804721