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Acrolein contributes to TRPA 1 up‐regulation in peripheral and central sensory hypersensitivity following spinal cord injury
Author(s) -
Park Jonghyuck,
Zheng Lingxing,
Acosta Glen,
VegaAlvarez Sasha,
Chen Zhe,
Muratori Breanne,
Cao Peng,
Shi Riyi
Publication year - 2015
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13352
Subject(s) - acrolein , spinal cord , transient receptor potential channel , neuropathic pain , dorsal root ganglion , chemistry , receptor , central nervous system , peripheral nerve injury , spinal cord injury , neuroscience , medicine , anesthesia , biochemistry , biology , catalysis , sciatic nerve
Abstract 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 ( TRPA 1) channel that exists in sensory neurons. Both acrolein and TRPA 1 mRNA are elevated post SCI , which contributes to the activation of TRPA 1 by acrolein and consequently, neuropathic pain. In the current study, we further showed that, post‐ SCI elevation of TRPA 1 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 TRPA 1 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 TRPA 1 mRNA at various locations when injected to the spinal cord. In addition, post‐ SCI elevation of TRPA 1 mRNA could be mitigated using acrolein scavengers. Both of these attributes support the critical role of acrolein in elevating TRPA 1 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 TRPA 1 receptor, and also by boosting the expression of TRPA 1. Finally, our data also further support the notion that acrolein scavenging may be an effective therapeutic approach to alleviate neuropathic pain after SCI.We propose that the trauma‐mediated elevation of acrolein causes neuropathic pain through at least two mechanisms: acrolein stimulates the production of transient receptor protein ankyrin 1 (TRPA1) in both central and peripheral locations, and it activates TRPA1 channels directly. Therefore, acrolein appears to be a critical factor in the pathogenesis of post‐SCI sensory hypersensitivity, becoming a novel therapeutic target to relieve both acute and chronic post‐SCI neuropathic pain.