Document Type

Honors Project On-Campus Access Only


Chronic pain resulting from spinal cord injuries (SCI) affects millions world-wide, and current therapeutics are largely ineffective, making investigation into the mechanisms behind this condition of paramount importance. Hypersensitivity following SCI occurs due to central sensitization, a process that includes increased membrane excitability, increased synaptic efficacy, and decreased inhibition of neurons in the spinal cord. Recent work has shown that activation of microglia after injury is critical to developing neuropathic pain and may mediate some of these neuronal changes. We have previously shown that the VGF-derived neuropeptide TLQP-21 is upregulated in injured neurons and contributes to the development and maintenance of hypersensitivity after peripheral nerve injury. TLQP-21 acts through the complement 3a receptor (C3aR1) on microglia, and we have shown that it acts to initiate a neuroimmune signaling pathway. This has not yet been studied in SCI, a central model of neuropathic pain. This thesis has used immunohistochemistry and behavioral assays to conclude that microglia and C3aR1 are upregulated in the spinal cord following spinal cord injury, and that this injury produces mechanical allodynia, thermal hyperalgesia, and spontaneous pain. Examining these novel molecular pathways that occur after injury could help to elucidate new targets to treat pain following SCI.



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