Calpain-2 Regulates TNF-α Expression Associated with Neuropathic Pain Following Motor Nerve Injury. (15th April 2018)

• Record Type: Journal Article
• Authors: Chen, Shao-Xia; Liao, Guang-Jie; Yao, Pei-Wen; Wang, Shao-Kun; Li, Yong-Yong; Zeng, Wei-an; Liu, Xian-Guo; Zang, Ying
• Is Part Of: Neuroscience. Volume 376(2018)
• Page Start: 142
• Page End: 151
• Publication Date: 2018-04-15
• Subjects: CALP2 calpain-2 -- DRGs dorsal root ganglias -- L5-VRT L5 ventral root transection -- NF-κB Nuclear factor-κB -- PFA paraformaldehyde -- SART specific alternation of rhythm in temperature -- SCI spinal cord injury -- TNF-α tumor necrosis factor-α; calpain-2 (CALP2) -- tumor necrosis factor-α (TNF-α) -- L5 ventral root transection (L5-VRT) -- dorsal root ganglias (DRG) -- spinal cord; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2018.02.023
• Languages: English
• ISSNs: 0306-4522

Abstract

Graphical abstract: CALP2 regulates TNF-α expression and allodynia after motor nerve injury. L5-VRT leads to upregulation of CALP2 and TNF-α in bilateral DRGs and spinal cord, thus inducing bilateral allodynia. Pretreatment of calpain inhibitor MDL28170 significantly reduces CALP2 and TNF-α expression levels and relieves bilateral allodynia. Introducing rr-CALP2 to the surface of L5 DRG of uninjured rats results in TNF-α overexpression in bilateral DRGs and spinal cord, and induces pain hypersensitivity. Highlights: Robust elevation of CALP2 and TNF-α in bilateral DRGs and spinal cord neurons following L5-VRT. TNF-α is co-localized with Calpain-2. CALP2 and TNF-α elevation by L5-VRT were inhibited by pretreatment with calpain inhibitor. Administration of CALP2 to rats without nerve injury further supported CALP2 regulates TNF-α. The linking of CALP2 and TNF-α provides a perspective for treating neuropathic pain. Abstract: Both calpain-2 (CALP2) and tumor necrosis factor-α (TNF-α) contribute to persistent bilateral hypersensitivity in animals subjected to L5 ventral root transection (L5-VRT), a model of selective motor fiber injury without sensory nerve damage. However, specific upstream mechanisms regulating TNF-α overexpression and possible relationships linking CALP2 and TNF-α have not yet been investigated in this model. We examined changes in CALP2 and TNF-α protein levels and alterations in bilateral mechanical threshold within 24 h following L5-VRT model injury. We observed robust elevation of CALP2 and TNF-α in bilateral dorsal root ganglias (DRGs) and bilateral spinal cord neurons. CALP2 and TNF-α protein induction by L5-VRT were significantly inhibited by pretreatment using the calpain inhibitor MDL28170. Administration of CALP2 to rats without nerve injury further supported a role of CALP2 in the regulation of TNF-α expression. Although clinical trials of calpain inhibition therapy for alleviation of neuropathic pain induced by motor nerve injury have not yet shown success, our observations linking CALP2 and TNF-α provide a framework of a systems' approach based perspective for treating neuropathic pain.