期刊
JOURNAL OF NEUROCHEMISTRY
卷 138, 期 2, 页码 328-338出版社
WILEY-BLACKWELL
DOI: 10.1111/jnc.13639
关键词
aldehyde; hyperreflexia; lipid peroxidation; phenelzine; proalgesic
资金
- Indiana State Department of Health [204200]
- National Institutes of Health [NS073636]
- Indiana CTSI Collaboration in Biomedical Translational Research (CBR/CTR) Pilot Program [RR025761]
- Project Development Teams pilot grant [TR000006]
- Science and Technology Commission of Shanghai Municipality, Shanghai, China [13430722100]
- Shanghai Bureau of Health, Shanghai, China [XBR2011024]
Currently there are no effective therapies available for the excruciating neuropathic pain that develops after spinal cord injuries (SCI). As such, a great deal of effort is being put into the investigation of novel therapeutic targets that can alleviate this pain. One such target is acrolein, a highly reactive aldehyde produced as a byproduct of oxidative stress and inflammation that is capable of activating the transient receptor potential ankyrin 1 (TRPA1) cation channel, known to be involved in the transmission and propagation of chronic neuropathic pain. One anti-acrolein agent, hydralazine, has already been shown to reduce neuropathic pain behaviors and offer neuroprotection after SCI. This study investigates another acrolein scavenger, phenelzine, for its possible role of alleviating sensory hypersensitivity through acrolein suppression. The results show that phenelzine is indeed capable of attenuating neuropathic pain behaviors in acute, delayed, and chronic administration schedules after injury in a rat model of SCI. In addition, upon the comparison of hydralazine to phenelzine, both acrolein scavengers displayed a dose-dependent response in the reduction of acrolein invivo. Finally, phenelzine proved capable of providing locomotor function recovery and neuroprotection of spinal cord tissue when administered immediately after injury for 2weeks. These results indicate that phenelzine may be an effective treatment for neuropathic pain after SCI and likely a viable alternative to hydralazine.
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