Acrolein contributes to TRPA1 up-regulation in peripheral and central sensory hypersensitivity following spinal cord injury

Jonghyuck Park, Lingxing Zheng, Glen Acosta, Sasha Vega-Alvarez, Zhe Chen, Breanne Muratori, Peng Cao, Riyi Shi

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35 Citations (SciVal)


Acrolein, an endogenous aldehyde, has been shown to be involved in sensory hypersensitivity after rat spinal cord injury (SCI), for which the pathogenesis is unclear. Acrolein can directly activate a pro-algesic transient receptor protein ankyrin 1 (TRPA1) channel that exists in sensory neurons. Both acrolein and TRPA1 mRNA are elevated post SCI, which contributes to the activation of TRPA1 by acrolein and consequently, neuropathic pain. In the current study, we further showed that, post-SCI elevation of TRPA1 mRNA exists not only in dorsal root ganglias but also in both peripheral (paw skin) and central endings of primary afferent nerves (dorsal horn of spinal cord). This is the first indication that pain signaling can be over-amplified in the peripheral skin by elevated expressions of TRPA1 following SCI, in addition over-amplification previously seen in the spinal cord and dorsal root ganglia. Furthermore, we show that acrolein alone, in the absence of physical trauma, could lead to the elevation of TRPA1 mRNA at various locations when injected to the spinal cord. In addition, post-SCI elevation of TRPA1 mRNA could be mitigated using acrolein scavengers. Both of these attributes support the critical role of acrolein in elevating TRPA1 expression through gene regulation. Taken together, these data indicate that acrolein is likely a critical causal factor in heightening pain sensation post-SCI, through both the direct binding of TRPA1 receptor, and also by boosting the expression of TRPA1. Finally, our data also further support the notion that acrolein scavenging may be an effective therapeutic approach to alleviate neuropathic pain after SCI.

Original languageEnglish
Pages (from-to)987-997
Number of pages11
JournalJournal of Neurochemistry
Issue number5
StatePublished - Dec 1 2015

Bibliographical note

Funding Information:
This work was supported by the Indiana State Department of Health (Grant # 204200 to RS), National Institutes of Health (Grant # NS073636 to RS), Indiana CTSI Collaboration in Biomedical Translational Research (CBR/CTR) Pilot Program Grant (Grant # RR025761 to RS), and Project Development Teams pilot grant (Grant #TR000006 to RS). Riyi Shi is the co-founder of Neuro Vigor, a star-up company with business interests of developing effective therapies for CNS neurodegenerative diseases and trauma. This work was funded by National Institute of Neurological Disorders and Stroke, (Grant/Award Number: ''NS073636'')

Publisher Copyright:
© 2015 International Society for Neurochemistry.


  • aldehyde
  • hydralazine
  • hyperreflexia
  • lipid peroxidation
  • proalgesic

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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