Research Article| Volume 379, P29-35, August 15, 2017

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Exogenous Acrolein intensifies sensory hypersensitivity after spinal cord injury in rat

  • Breanne Butler
    Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA
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  • Glen Acosta
    Department of Basic Medical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA
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  • Riyi Shi
    Corresponding author at: Department of Basic Medical Sciences, Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, 47907., United States.
    Department of Basic Medical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA

    Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA
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      • Inhalation of acrolein and cigarette smoke worsen pain after spinal cord injury
      • Cigarette smoke threatens the vulnerable injured area in the nervous system
      • Acrolein scavenging can attenuate post-SCI pain during acrolein exposure


      Acrolein, an α,β-unsaturated aldehyde associated with oxidative stress, is also a major toxic component of tobacco cigarette smoke, which has been reported in the clinic to coincide with the exacerbation of neuropathic pain after SCI. Previous reports have shown that acrolein involvement in spinal cord injury (SCI) is crucial to the development and persistence of neuropathic pain. Through the activation and upregulation of the transient receptor protein ankyrin-1 (TRPA1) cation channel, acrolein is capable of sensitizing the central nervous system in the acute and chronic stages of SCI. Here, we report that the acute or delayed nasal exposure of acrolein, apart from cigarette smoke but at concentrations similar to that found in cigarette smoke, resulted in increased neuropathic pain behaviors in a rat model of contusion SCI. We also found that this hyperalgesia occurred concurrently with an augmentation in systemic acrolein, detected by an acrolein-glutathione metabolite in the urine. The application of an acrolein scavenger, phenelzine, was shown to reduce the hyperalgesic effect of acrolein inhalation. The previously determined ability of acrolein to bind to and activate the TRPA1 channel and elicit algesic responses may be a mechanism of the phenomenon seen in this study. Upon the exposure to actual cigarette smoke after SCI, intensified neuropathic pain behaviors were also observed and persisted for at least 1 week after the cessation of the exposure period. Taken together, these results indicate that cigarette smoke, through mechanisms involving acrolein, poses a threat to the vulnerable CNS after SCI and can contribute to neuropathic pain. This investigation also provides further evidence for the potential utility of acrolein scavengers as a therapeutic strategy in SCI-resultant neuropathic pain.

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