Somatosensory cortex undergoes maladaptive reorganization with neuropathic pain development after spinal cord injury

Gary Howard Blumenthal

doi:10.17918/00000534

Spinal cord injury (SCI) is a severely debilitating condition that affects millions of individuals worldwide. A common complication after SCI is the development of chronic neuropathic pain, which is often described as excruciating and can occur spontaneously or through very light tactile touch, such as when clothes brush up against the skin. Current standard treatments for neuropathic pain are limited in their effectiveness and would greatly benefit from a more complete understanding of the physiological mechanisms that perpetuate this dysregulation of the nervous system. Pain is a cognitive process, as the brain is required to experience pain. The primary somatosensory cortex (S1) is known to process pain information, and increasing evidence suggests that it plays a key role in the development of neuropathic pain after injury. S1 can become plastic after a neurological deficit, such that sensory representations in the cortex become altered in a process known as cortical reorganization. In human patients, this cortical reorganization may occur proportionally to the amount of neuropathic pain that is experienced. However, little is known about how this reorganization occurs or if S1 should be considered a therapeutic target for neuropathic pain. Additionally, lack of effective animal modeling limits our understanding of this phenomenon. In this thesis work, we first refine a rodent model of SCI that produces distinct populations of animals that either develop or do not develop neuropathic pain. We then perform several detailed electrophysiological mapping studies to gain an understanding of both spinal and cortical trunk receptive fields in the uninjured animal. Cortical reorganization is then assessed in the post-injury animal to identify plastic changes that may be associated with neuropathic pain development. Additionally, we analyze mRNA expression in the cortex to understand local transcriptional changes occurring that may contribute to this plasticity. Our results indicate that with a contusive SCI at the T10 level, animals can be separated into distinct populations based on the development of at-level pain, or pain that arises close to the lesion site. Further, the area on the trunk that develops pain in the post-injury animal can be isolated within the somatotopy of trunk S1, and this representation is found to reorganize in animals with neuropathic pain such that it expands into putative forelimb, ventral trunk, and lower trunk regions. Additionally, genes in the cortex related to neuroinflammation and plasticity are differentially regulated in animals with neuropathic pain, supporting the S1 cortex as an important structure for potential therapeutic intervention for neuropathic pain development.

Somatosensory cortex undergoes maladaptive reorganization with neuropathic pain development after spinal cord injury

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Somatosensory cortex undergoes maladaptive reorganization with neuropathic pain development after spinal cord injury

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