Acrolein as a novel therapeutic target for spinal cord injury induced neuropathic pain

<p>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.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biomedical Engineering

Year

2014

Author dc:creator

• Park, Jonghyuck

Contributors dc:contributor

• Riyi Shi
• Eric Nauman
• Kevin Otto
• Bradley Duerstock

• Biology
• Biomedical Engineering and Bioengineering
• Neuroscience and Neurobiology

Repository record dc:identifier

https://docs.lib.purdue.edu/open_access_dissertations/342

OAI identifier oai:identifier

oai:docs.lib.purdue.edu:open_access_dissertations-1467