Butler Breanne, Acosta Glen, Shi Riyi
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA.
Department of Basic Medical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA.
J Neurol Sci. 2017 Aug 15;379:29-35. doi: 10.1016/j.jns.2017.05.039. Epub 2017 May 22.
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 1week 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.
丙烯醛是一种与氧化应激相关的α,β-不饱和醛，也是香烟烟雾中的一种主要有毒成分，临床报告显示其与脊髓损伤（SCI）后神经性疼痛的加剧同时出现。先前的报告表明，丙烯醛参与脊髓损伤对神经性疼痛的发生和持续至关重要。通过激活和上调瞬时受体蛋白锚蛋白-1（TRPA1）阳离子通道，丙烯醛能够在SCI的急性和慢性阶段使中枢神经系统敏感化。在此，我们报告，除香烟烟雾外，以与香烟烟雾中发现的浓度相似的浓度对大鼠进行丙烯醛急性或延迟鼻腔暴露，会导致挫伤性SCI大鼠模型中神经性疼痛行为增加。我们还发现，这种痛觉过敏与尿液中丙烯醛-谷胱甘肽代谢物检测到的全身丙烯醛增加同时发生。应用丙烯醛清除剂苯乙肼可降低丙烯醛吸入的痛觉过敏作用。先前确定的丙烯醛结合并激活TRPA1通道并引发痛觉反应的能力可能是本研究中所见现象的一种机制。在SCI后暴露于实际香烟烟雾中时，也观察到神经性疼痛行为加剧，并且在暴露期停止后至少持续1周。综上所述，这些结果表明，香烟烟雾通过涉及丙烯醛的机制，对SCI后脆弱的中枢神经系统构成威胁，并可导致神经性疼痛。本研究还为丙烯醛清除剂作为SCI所致神经性疼痛的治疗策略的潜在效用提供了进一步证据。
