Pain Input After Spinal Cord Injury (SCI) Undermines Long-Term Recovery and Engages Signal Pathways That Promote Cell Death.
Pain Input After Spinal Cord Injury (SCI) Undermines Long-Term Recovery and Engages Signal Pathways That Promote Cell Death.
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DOI：
10.3389/fnsys.2018.00027
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发表时间：
2018
影响因子：
3
通讯作者：
Grau JW
中科院分区：
文献类型：
--
作者：
Turtle JD;Strain MM;Reynolds JA;Huang YJ;Lee KH;Henwood MK;Garraway SM;Grau JW
脊髓挫伤尾部的疼痛（伤害性）输入增加了组织损失并损害长期恢复。据推测，伤害性刺激具有这种效应，因为它涉及在中枢通路中产生过度兴奋状态的无髓鞘疼痛（C）纤维。本文探讨了这个问题，通过评估辣椒素的影响，它激活C-纤维，表达瞬时受体电位香草素受体-1（TRPV 1）。大鼠接受下胸部（T11）挫伤，第二天将辣椒素施加到一只后爪。为了比较，其他动物接受了强度与C纤维有关的有害电刺激。两种形式的刺激引起类似水平的c-fos mRNA表达，伤害性激活的细胞标志物，并损害长期行为恢复。然后进行细胞测定以比较休克和辣椒素治疗的急性效应。两种形式的伤害性刺激增加了肿瘤坏死因子（TNF）和caspase-3的表达，从而促进了凋亡细胞的死亡。休克，而不是辣椒素，增强与细胞死亡相关的信号的表达[半胱天冬酶-1，白细胞介素-1 β（IL-1 β）]。焦亡与P2 X7受体的激活和三磷酸腺苷（ATP）通过泛连接蛋白-1通道的外流有关。用Brilliant Blue G（BBG）阻断P2 X7受体可减少休克大鼠中与焦萎细胞死亡相关的信号表达。用丙磺舒阻断泛连接蛋白-1通道反而具有相反的效果。BBG增强了长期恢复并降低了对施加于腰带区域的机械刺激的反应性（慢性疼痛的指数），但不能阻断伤害性刺激的不良作用。结果表明，损伤后的C-纤维输入损害长期恢复，这种影响可能是因为它诱导凋亡细胞死亡。
Pain (nociceptive) input caudal to a spinal contusion injury increases tissue loss and impairs long-term recovery. It was hypothesized that noxious stimulation has this effect because it engages unmyelinated pain (C) fibers that produce a state of over-excitation in central pathways. The present article explored this issue by assessing the effect of capsaicin, which activates C-fibers that express the transient receptor potential vanilloid receptor-1 (TRPV1). Rats received a lower thoracic (T11) contusion injury and capsaicin was applied to one hind paw the next day. For comparison, other animals received noxious electrical stimulation at an intensity that engages C fibers. Both forms of stimulation elicited similar levels of c-fos mRNA expression, a cellular marker of nociceptive activation, and impaired long-term behavioral recovery. Cellular assays were then performed to compare the acute effect of shock and capsaicin treatment. Both forms of noxious stimulation increased expression of tumor necrosis factor (TNF) and caspase-3, which promotes apoptotic cell death. Shock, but not capsaicin, enhanced expression of signals related to pyroptotic cell death [caspase-1, inteleukin-1 beta (IL-1ß)]. Pyroptosis has been linked to the activation of the P2X7 receptor and the outward flow of adenosine triphosphate (ATP) through the pannexin-1 channel. Blocking the P2X7 receptor with Brilliant Blue G (BBG) reduced the expression of signals related to pyroptotic cell death in contused rats that had received shock. Blocking the pannexin-1 channel with probenecid paradoxically had the opposite effect. BBG enhanced long-term recovery and lowered reactivity to mechanical stimulation applied to the girdle region (an index of chronic pain), but did not block the adverse effect of nociceptive stimulation. The results suggest that C-fiber input after injury impairs long-term recovery and that this effect may arise because it induces apoptotic cell death.
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影响因子：
2.7
作者：
Hook, Michelle A.;Liu, Grace T.;Grau, James W.
通讯作者：
Grau, James W.
影响因子：
5.8
作者：
Duprez, Linde;Wirawan, Ellen;Vandenabeele, Peter
通讯作者：
Vandenabeele, Peter
影响因子：
1.9
作者：
Grau, JW;Barstow, DG;Joynes, RL
通讯作者：
Joynes, RL
影响因子：
1.9
作者：
Crown, ED;Ferguson, AR;Grau, JW
通讯作者：
Grau, JW
DOI：
10.1085/jgp.201210875
发表时间：
2012-11
期刊：
The Journal of general physiology
影响因子：
--
作者：
Bernier LP
通讯作者：
Bernier LP