Date of Award
Fall 2014
Degree Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Biomedical Engineering
First Advisor
Riyi Shi
Committee Chair
Riyi Shi
Committee Member 1
Eric Nauman
Committee Member 2
Kevin Otto
Committee Member 3
Bradley Duerstock
Abstract
Despite years of research, post-spinal cord injury (SCI) chronic neuropathic pain remains refractory to treatment and drastically impairs quality of life for SCI victims beyond paralysis. Although inflammation and free radicals contribute to neuropathic pain in SCI, the mechanism is not completely clear. We have recently demonstrated that acrolein, a product and catalyst of lipid peroxidation, induces a vicious cycle of oxidative stress, amplifying its effects and perpetuating oxidative stress and inflammation. In the current study, we have confirmed that acrolein is elevated significantly at least two weeks post-SCI which coincides with the emergence of hyperalgesia (mechanical, cold and thermal). Furthermore, anti-acrolein treatment hydalazine can reverse pain behavior. Consistent with this, acrolein is a known ligand that directly excites transient receptor potential ankyrin 1 receptor (TRPA1) in DRG nociceptive neurons to transmit pain sensation. In addition, we have observed a significant increase of monocyte chemoattractant protein-1 (MCP1), a pro-inflammatory chemokine that is also known be increased upon acrolein stimulation and capable of sensitizing TRPA1 following SCI. Similarly, we observed a heightened excitatory response of DRG sensory neurons to current stimulation in the presence of acrolein, indicating an enhanced sensitivity of DRG cells to acrolein post SCI. In summary, acrolein may play an important role in the post SCI hyperalgesia through greater direct binding to TRPA1 and enhanced sensitivity of DRG to acrolein via MCP1-mediated pathway.
Recommended Citation
Park, Jonghyuck, "Acrolein as a novel therapeutic target for spinal cord injury induced neuropathic pain" (2014). Open Access Dissertations. 342.
https://docs.lib.purdue.edu/open_access_dissertations/342
Included in
Biology Commons, Biomedical Engineering and Bioengineering Commons, Neuroscience and Neurobiology Commons