Dissecting the role of inflammation in chronic spinal cord injury pain
Chronic pain is one of the most debilitating sequelae of neurotrauma and affects the quality of life of up to 80% of patients with spinal cord injury (SCI). Whether the resulting pain is due to effects of the immune response to injury (inflammatory pain), changes to peripheral/central neurons (neuropathic pain), or a combination of the two remains unknown. First order pain-‐sensing (nociceptive) sensory neurons lie in the peripheral dorsal root ganglia (DRG), respond to peripheral stimuli, and are the first to process the sensation of pain. These bipolar neurons extend a peripheral process into the skin and organs and a central process into the dorsal horn of the spinal cord where they synapse with second-‐order neurons relaying this information to the brain for processing. These central processes are bathed in the inflammatory environment of the injured CNS, which has been shown to alter their function. Furthermore, there is now evidence that inflammatory markers including cytokines are upregulated in the DRGs as well, likely spurring on changes in nociceptor activity.
Whether this peripheral inflammatory response affects pain behaviors remains unknown. We propose using a bedside-‐to-‐bench-‐and back approach to identify specific protein mediators that can alter nociceptor activity and chronic SCI pain in an effort to block their maladaptive properties and thus mitigate pain outcomes. Using blood and cerebrospinal fluid (CSF) from patients with and without chronic SCI pain, we will use proteomics techniques to identify specific mediators that may mediate painful outcomes. These results will be validated with a mouse model of chronic contusive injury using strains with divergent inflammatory outcomes to identify proteins expressed in both human and animal models. The function of specific proteins will be characterized in the pathogenesis of chronic SCI pain in the animal model, which will hopefully lead to a clinical trial or the development of new therapeutics.
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