Accounting for the Delay in the Transition from Acute to Chronic Pain: Axonal and Nuclear Mechanisms
Accounting for the Delay in the Transition from Acute to Chronic Pain: Axonal and Nuclear Mechanisms
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DOI：
10.1523/jneurosci.5147-13.2015
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发表时间：
2015-01-14
影响因子：
5.3
通讯作者：
Levine, Jon D.
中科院分区：
文献类型：
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作者：
Ferrari, Luiz F.;Bogen, Oliver;Levine, Jon D.
急性损伤产生痛觉过敏启动，这是一种伤害感受器的神经可塑性变化，可显著延长炎症介质诱导的痛觉过敏。在急性启动性损伤后，启动有72小时的延迟，其潜在机制尚不清楚。我们假设延迟是由于信号从外周终端传播到细胞体然后返回外周终端所需的时间。我们报告说，当在Sprague Dawley大鼠脊髓中施用致痛觉引发的诱导剂（单核细胞趋化蛋白1）时，在外周末梢检测到引发，其延迟明显短于外周应用时。脊髓诱导启动不仅在前列腺素E-2 （PGE(2)）呈递给外周伤害感受器末梢时被检测到，而且在鞘内呈递给脊髓中央末梢时也被检测到。此外，当启动诱导剂在爪中使用时，脊髓中可以检测到启动（鞘内PGE引起的长时间痛觉过敏(2)），但只有当机械刺激呈现在启动诱导剂使用的一侧的爪上时才会检测到启动。脊髓和外周诱导的启动可通过鞘内对核转录因子CREB mRNA的寡脱氧核苷酸反义来阻止。最后，蛋白翻译抑制剂只有在注射PGE(2)的部位才能逆转痛感引发，这表明从细胞体传递到外周末梢的信号不是新翻译的蛋白，而可能是新表达的mRNA。
Acute insults produce hyperalgesic priming, a neuroplastic change in nociceptors that markedly prolongs inflammatory mediator-induced hyperalgesia. After an acute initiating insult, there is a 72 h delay to the onset of priming, for which the underlying mechanism is unknown. We hypothesized that the delay is due to the time required for a signal to travel from the peripheral terminal to the cell body followed by a return signal to the peripheral terminal. We report that when an inducer of hyperalgesic priming (monocyte chemotactic protein 1) is administered at the spinal cord of Sprague Dawley rats, priming is detected at the peripheral terminal with a delay significantly shorter than when applied peripherally. Spinally induced priming is detected not only when prostaglandin E-2 (PGE(2)) is presented to the peripheral nociceptor terminals, but also when it is presented intrathecally to the central terminals in the spinal cord. Furthermore, when an inducer of priming is administered in the paw, priming can be detected in spinal cord (as prolonged hyperalgesia induced by intrathecal PGE(2)), but only when the mechanical stimulus is presented to the paw on the side where the priming inducer was administered. Both spinally and peripherally induced priming is prevented by intrathecal oligodeoxynucleotide antisense to the nuclear transcription factor CREB mRNA. Finally, the inhibitor of protein translation reversed hyperalgesic priming only when injected at the site where PGE(2) was administered, suggesting that the signal transmitted from the cell body to the peripheral terminal is not a newly translated protein, but possibly a newly expressed mRNA.