Burst-Like Subcutaneous Electrical Stimulation Induces BDNF-Mediated, Cyclotraxin B-Sensitive Central Sensitization in Rat Spinal Cord.
Burst-Like Subcutaneous Electrical Stimulation Induces BDNF-Mediated, Cyclotraxin B-Sensitive Central Sensitization in Rat Spinal Cord.
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DOI：
10.3389/fphar.2018.01143
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发表时间：
2018
影响因子：
5.6
通讯作者：
Constandil L
中科院分区：
文献类型：
--
作者：
Retamal J;Reyes A;Ramirez P;Bravo D;Hernandez A;Pelissier T;Villanueva L;Constandil L
鞘内给予脑源性神经营养因子（BDNF）可诱导长期增强（LTP）并在脊髓中产生持久的中枢致敏，从而模拟慢性疼痛，但这些观察结果与慢性疼痛机制的相关性尚不确定。由于高频皮下电刺激（SES）方案激活c -纤维可引起脊髓BDNF释放并诱导脊髓LTP，因此我们认为应用这种方案将是产生持久的BDNF介导的中枢致敏的充分条件。结果显示，在大鼠脚趾上应用爆发样SES可产生(1)持续3周以上的痛觉过敏快速诱导，(2)c反射活动早期升高，随后上卷评分升高，持续1周以上，(3)BDNF蛋白水平和磷酸化TrkB早期升高，随后下降，持续1周以上。这些变化可以通过在SES前使用TrkB拮抗剂cyclotraxin-B来预防，而在SES后3天使用cyclotraxin-B可以逆转痛觉过敏。结果表明，中枢致敏的机制首先涉及可能来自神经元的BDNF释放，然后可能是胶质细胞BDNF和pTrkB的短暂表达增加，从而将早期致敏转变为晚期。
Intrathecal administration of brain derived neurotrophic factor (BDNF) induces long-term potentiation (LTP) and generates long-lasting central sensitization in spinal cord thus mimicking chronic pain, but the relevance of these observations to chronic pain mechanisms is uncertain. Since C-fiber activation by a high-frequency subcutaneous electrical stimulation (SES) protocol causes spinal release of BDNF and induces spinal cord LTP, we propose that application of such protocol would be a sufficient condition for generating long-lasting BDNF-mediated central sensitization. Results showed that application of burst-like SES to rat toes produced (i) rapid induction of hyperalgesia that lasted for more than 3 weeks, (ii) early increase of C-reflex activity followed by increased wind-up scores lasting for more than 1 week, and (iii) early increase followed by late decrease in BDNF protein levels and phosphorylated TrkB that lasted for more than 1 week. These changes were prevented by the TrkB antagonist cyclotraxin-B administered shortly before SES, while hyperalgesia was reversed by cyclotraxin-B administered 3 days after SES. Results suggest that mechanisms underlying central sensitization first involve BDNF release of probably neuronal origin, followed by brief increased expression of likely glial BDNF and pTrkB that could switch early phase sensitization into late one.
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影响因子：
6.1
作者：
Ding, Xu;Cai, Jie;Xing, Guo-Gang
通讯作者：
Xing, Guo-Gang
影响因子：
7.4
作者：
Kawamata, M;Omote, K
通讯作者：
Omote, K
影响因子：
5.5
作者：
BLISS, TVP;LOMO, T
通讯作者：
LOMO, T
影响因子：
4
作者：
Constandil, Luis;Goich, Mariela;Pelissier, Teresa
通讯作者：
Pelissier, Teresa
影响因子：
5.3
作者：
Klein, T;Magerl, W;Treede, RD
通讯作者：
Treede, RD