Highlights
- •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
Abstract
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.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: May 22, 2017
Accepted:
May 21,
2017
Received in revised form:
April 30,
2017
Received:
January 6,
2017
Identification
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© 2017 Published by Elsevier B.V.
