Defining the Role of Mechanical Signals During Nerve Root Compression in the Development of Sustained Pain and Neurophysiological Correlates that Develop in the Injured Tissue and Spinal Cord

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Doctor of Philosophy (PhD)
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Bioengineering
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electrophysiology
glutamate
glutamate transporter
injury
nerve root
Biomechanics
Biomedical
Neuroscience and Neurobiology
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2014-08-21T20:13:00-07:00
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Abstract

Cervical nerve root injury commonly leads to pain. The duration of an applied compression has been shown to contribute to both the onset of persistent pain and also the degree of spinal cellular and molecular responses related to nociception that are produced. This thesis uses a rat model of a transient cervical nerve root compression to study how the duration of an applied compression modulates both peripherally-evoked activity in spinal cord neurons during a root compression and the resulting neuronal and glutamatergic responses in the nerve root and spinal cord. Studies define the compression duration threshold that inhibits peripherally-evoked action potentials in the spinal cord during a root compression to be at 6.6±3.0 minutes and this is similar to the threshold for eliciting persistent mechanical allodynia after a cervical root compression that lies between 3 and 10 minutes. Furthermore, neurotransmission remains inhibited for at least 10 minutes after a painful nerve root compression and this may contribute to the subsequent development of neuropathology in the root, spinal neuronal hyperexcitability, downregulation of spinal GLT-1 and upregulation of spinal GLAST at day 7. Additional studies examine the role of the spinal glutamatergic system in mediating radicular pain by administering Riluzole to inhibit glutamate release at day 1 or ceftriaxone daily to upregulate spinal GLT-1, separately. Both treatments abolished behavioral sensitivity and the associated neuronal hyperexcitability that is normally observed in the deep laminae of the dorsal horn. Additionally, Riluzole mitigated the axonal neuropathology in the root that normally develops by day 7 while ceftriaxone restored the spinal expression of GLAST. Together these studies identify how one aspect of nerve root biomechanics, compression duration, modulates neuronal and glutamatergic responses in the nerve root and spinal cord that are associated with cervical radicular pain. Day 1 was identified as a critical time-point when inhibiting glutamate signaling in the central nervous system can prevent persistent nerve root-mediated pain that is likely maintained by downregulation of spinal GLT-1. Finally, these studies suggest that primary afferent regulation of spinal GLT-1 may have a critical role in transducing the biomechanics of a nerve root compression into radicular pain.

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Beth A. Winkelstein
Date of degree
2013-01-01
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