Mitigation of sensory and motor deficits by acrolein scavenger phenelzine in a rat model of spinal cord contusive injury

Journal of Neurochemistry - Tập 138 Số 2 - Trang 328-338 - 2016
Zhe Chen1,2, Jonghyuck Park3,4, Breanne Butler4, Glen Acosta3, Sasha Vega‐Alvarez3, Lingxing Zheng3,4, Jonathan Tang3,4, Robyn McCain5, Wenpeng Zhang4, Zheng Ouyang6,4, Peng Cao1,2, Riyi Shi3,4
1Department of Orthopedics, Rui-Jin Hospital, School of Medicine, Shanghai Jiao-tong University, Institute of Trauma and Orthopedics, Shanghai, China.
2Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine Shanghai Institute of Traumatology and Orthopedics Rui-Jin Hospital Shanghai Jiao-tong University School of Medicine Shanghai China
3Department of Basic Medical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA
4Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA
5Purdue Translational Pharmacology Bindley Bioscience Center Purdue University West Lafayette IN USA
6Department of Chemistry, Purdue University, West Lafayette, IN USA

Tóm tắt

AbstractCurrently 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 in vivo. Finally, phenelzine proved capable of providing locomotor function recovery and neuroprotection of spinal cord tissue when administered immediately after injury for 2 weeks. These results indicate that phenelzine may be an effective treatment for neuropathic pain after SCI and likely a viable alternative to hydralazine. imageWe have shown that phenelzine can attenuate neuropathic pain behavior in acute, delayed, and chronic administration in post‐SCI rats. This was accompanied by a dose‐dependent reduction in an acrolein metabolite in urine and an acrolein adduct in spinal cord tissue, and the suppression of TRPA1 over‐expression in central and peripheral locations post‐trauma. Acrolein scavenging might be a novel therapeutic strategy to reduce post‐SCI neuropathic pain.

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Thông tin xuất bản

Journal of Neurochemistry

Tập 138 Số 2

328-338

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