All ETDs from UAB

Advisory Committee Chair

William R Reed

Advisory Committee Members

Barbara Gower

Michelle Gray

Christopher P Hurt

Robert E Sorge

Ceren Yarar-Fisher

Document Type


Date of Award


Degree Name by School

Doctor of Philosophy (PhD) School of Health Professions


Low back pain (LBP), a condition characterized by pain experienced between the 12th rib margin and gluteal folds, is a prevalent health problem that affects an ever-increasing population worldwide. First-line treatment for LBP often involves non-pharmacological approaches, including spinal manipulative therapy (SMT), which has demonstrated mild-to-moderate clinical efficacy. However, despite its therapeutic benefits, the physiological mechanisms underlying the analgesic effects of SMT in LBP are still not well understood. Recent evidence suggests that sensitization of peripheral and central nervous system structures contribute to the progression and maintenance of LBP with inflammatory cytokines, reactive glial cells, and/or aberrant muscle spindle activity playing an unspecified role. This dissertation involved three projects with the overarching goal to better characterize pre-clinical models of LBP and to elucidate potential neurophysiological mechanisms underlying LBP and/or SMT which could ultimately contribute to SMT’s clinical efficacy in alleviating LBP. The first project investigated cytokine levels in the cerebrospinal fluid and astrocyte reactivity in the spinal cord dorsal horn as potential markers of LBP, and their response to spinal mobilization (SM) treatment in a unilateral trunk nerve growth factor (NGF)-induced LBP animal model. Our results indicated that NGF injection led to a significant increase in spontaneous pain, reduced ipsilateral hind paw Von Frey thresholds, and higher glial fibrillary acidic protein (GFAP) in the spinal cord deep dorsal horn compared to control. Additionally, the NGF+SM group showed lower spontaneous pain scores on Days 14 and 17, and lower GFAP expression in the deep dorsal horn compared to the NGF group suggesting SM’s treatment might: a) alleviate spontaneous pain and/or pain-like behavior, b) reduce astrocyte activation in the deep dorsal horn of the spine, and c) alleviate remote (not local) evoked mechanical allodynia in conditions of established muscular LBP. The last two projects determined the relationship between high-velocity low-amplitude spinal manipulation (HVLA-SM) parameters and immediate lumbar muscle spindle responsiveness in two distinct non-inflammatory feline experimental preparations in anticipation of investigating similar changes in muscle spindle responses to HVLA-SM in an NGF-induced LBP feline model. HVLA-SM thrust magnitudes of 55% body weight (BW) were more likely to alter muscle spindle afferent (MSA) frequency discharge immediately following the thrust compared to 25% or 85%BW, while thrust duration parameters between 25-250 ms did not elicit significantly different MSA responsiveness. Additionally, in preparations of increased spinal joint stiffness (via single or double spinal facet joint fixations), varied thrust durations (0-250 ms) and thrust locations (L4 vs. L6) did not significantly alter post-HVLA-SM MSA responsiveness. Taken together, these findings indicate that thrust parameters such as magnitude may have a more significant role in modulating immediate muscle spindle responsiveness than thrust duration or thrust location. Collectively, these distinct lines of investigation further characterized a relatively new experimental model of muscular LBP and provided greater insights into the physiological mechanisms associated with LBP and muscle spindle response to SMT so as to better inform future research efforts and potential mechanisms of nonpharmacological LBP treatment. In future studies, we recommend that limitations of the current studies be addressed including (1) inclusion of both biological sexes; (2) temporal delineation of neuroinflammatory biomarkers; (3) investigation of astrocytic morphological changes and phenotypic profiles; (4) investigation of longer term (>2s) MSA responsiveness following the HVLA-SM thrust in an NGF-induced model of LBP.



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