Inactivity Enhances SCI-Induced Dysfunction and Both Central and Peripheral Pain-Related Pathologies
Abstract
There is now outstanding evidence to show that exercise is medicine, however the converse to that, conceptually, is that inactivity is toxic. Spinal cord injury induces an immediate, profound, and lasting inactivity that we have begun to model in the rat using inactivity/immobility strategies. Our results suggest that inactivity has a substantial and multi-system negative impact that includes cardiovascular, muscle, and neurons in the dorsal root ganglia. We have also discovered that physical therapy-based hindlimb muscle stretching, developed to model clinical therapies to reduce spasticity and abrogate contractures, actually induces a dramatic drop in locomotor function, and that this negative impact is dependent on the presence of a major class of nociceptive C-fiber. Nociceptive C-fibers are known to sprout and to become sensitized after spinal cord injury, and these post-injury changes are activity/exercise dependent. Because nociceptors participate in both central and peripheral inflammatory processes we hypothesize that they are key players in the multi-system dysfunction. The proposed work will focus on understanding how inactivity/immobility influences dysfunction and the roles played by nociceptive C-fibers in that process. We will use the primary approach of housing conditions to dramatically restrict or enhance activity, and clinically relevant models of manual therapy (massage) and both passive and applied exercise. We will explore the time-course of how activity/inactivity can influence nociceptor changes (acute to chronic), and how these clinically relevant approaches can influence long-term functional outcomes (locomotor and sensory function), including markers of chronic and neuropathic pain. Because the focus of our study is clinically relevant and deals with current practices, these changes could be brought about in the clinic quickly, within just a few years, to potentially have a significant impact on the trajectory of recovery and long-term cost of patient care.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2211011
Entities
People
- David K Magnuson
Organizations
- United States Army
- University of Louisville