Contralateral paw sensitization following injection of endothelin-1: effects of local anesthetics differentiate peripheral and central processes.

Contralateral paw sensitization following injection of endothelin-1: effects of local anesthetics differentiate peripheral and central processes.
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DOI:
10.1016/j.neuroscience.2009.10.049
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发表时间:
2010-01-20
期刊:
影响因子:
3.3
通讯作者:
Strichartz, G. R.
Strichartz, G. R.
中科院分区:
医学3区
文献类型:
--
作者:
Khodorova, A.;Strichartz, G. R.

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已知将肽内皮素-1(ET-1)皮下注射到大鼠的足垫中会引起快速、短暂的同侧机械和热致敏以及伤害性后爪退缩。在这里,我们报告说,局部注射ET-1(2纳摩尔)到一个后爪缓慢敏感的对侧爪化学和机械刺激。与第一次注射相比,第二次注射相同剂量的ET-1 24小时后递送到对侧爪中,后爪退缩反应增加1.5-2倍。ET-1后24小时,对侧爪也出现了对福尔马林反应第二阶段期间退缩次数的类似增加。在同侧ET-1注射后24 h,对侧对von Frey毛的缩爪阈值降低约55%。ET-1皮下注射在一个节段无关的位置,颈部中线,没有引起爪致敏,避免了全身性的作用途径。局部麻醉阻滞同侧坐骨神经在同侧ET-1的初始反应期间防止对侧敏化,表明局部传入传递的重要性,虽然同侧脱敏没有改变。这些研究结果表明,外周ET-1的行动导致中央敏化,改变了选定的刺激反应。
Subcutaneous injection of the peptide endothelin-1 (ET-1) into the rat’s footpad is known to cause rapid, transient ipsilateral mechanical and thermal sensitization and nocifensive hind paw flinching. Here we report that local injection of ET-1 (2 nmoles) into one hind paw slowly sensitizes the contralateral paw to chemical and mechanical stimulation. There was a 1.5–2-fold increase in the hind paw flinching response, over that from the first injection, to a second injection of the same dose of ET-1 delivered 24 h later into the contralateral paw. A similar increase in the number of flinches during the second phase of the response to formalin also occurred in the contralateral paw 24 h after ET-1. The contralateral paw withdrawal threshold to von Frey hairs was lowered by ~ 55% at 24 h after ipsilateral ET-1 injection. ET-1 injected subcutaneously at a segmentally unrelated location, the nuchal midline, caused no sensitization of the paws, obviating a systemic route of action. Local anesthetic block of the ipsilateral sciatic nerve during the period of initial response to ipsilateral ET-1 prevented contralateral sensitization, indicating the importance of local afferent transmission, although ipsilateral desensitization was not changed. These findings suggest that peripheral ET-1 actions lead to central sensitization that alters responses to selected stimuli.
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