Long-term potentiation at C-fibre synapses by low-level presynaptic activity in vivo.

Long-term potentiation at C-fibre synapses by low-level presynaptic activity in vivo.
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DOI:
10.1186/1744-8069-4-18
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发表时间:
2008-05-28
期刊:
影响因子:
3.3
通讯作者:
Sandkuehler, Juergen
Sandkuehler, Juergen
中科院分区:
医学3区
文献类型:
--
作者:
Drdla, Ruth;Sandkuehler, Juergen

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炎症、创伤或神经损伤会触发C纤维的低水平活动,并可能导致持久的痛觉过敏。初级传入C纤维突触的长时程增强(LTP)被认为是某些形式的痛觉过敏的基础。然而,在以前的研究中,C纤维的高频而非低频条件刺激已被用于在疼痛通路中诱导LTP。最近,我们可以表明,在C纤维强度条件低频刺激(LFS)诱导LTP在体外以及在完整的动物,即与紧张性下行抑制完全活跃。在切片制备中,这种形式的LTP需要突触后Ca 2+浓度的升高和Ca 2+依赖性信号通路的激活。在这里,我们研究了这种新形式的LTP在体内的信号转导机制。我们发现,导致LFS诱导的LTP的信号转导途径包括激活神经激肽1和N-甲基-D-天冬氨酸受体,从细胞内储存和通过T型电压依赖性Ca ~(2+)通道升高[Ca ~(2+)]i,激活磷脂酶C,蛋白激酶C和Ca ~(2+)-钙调蛋白依赖性激酶II。这些通路与导致动物和人类痛觉过敏的通路相匹配。因此,我们建议,LTP引起的低水平活动的C-纤维可能是某些形式的痛觉过敏。
Inflammation, trauma or nerve injury trigger low-level activity in C-fibres and may cause long-lasting hyperalgesia. Long-term potentiation (LTP) at synapses of primary afferent C-fibres is considered to underlie some forms of hyperalgesia. In previous studies, high- but not low-frequency conditioning stimulation of C-fibres has, however, been used to induce LTP in pain pathways. Recently we could show that also conditioning low-frequency stimulation (LFS) at C-fibre intensity induces LTP in vitro as well as in the intact animal, i.e. with tonic descending inhibition fully active. In the slice preparation, this form of LTP requires a rise in postsynaptic Ca2+-concentration and activation of Ca2+-dependent signalling pathways. Here, we investigated the signalling mechanisms underlying this novel form of LTP in vivo. We found that the signal transduction pathways causing LFS-induced LTP in vivo include activation of neurokinin 1 and N-methyl-D-aspartate receptors, rise of [Ca2+]i from intracellular stores and via T-type voltage-dependent Ca2+ channels, activation of phospholipase C, protein kinase C and Ca2+-calmodulin dependent kinase II. These pathways match those leading to hyperalgesia in behaving animals and humans. We thus propose that LTP induced by low-level activity in C-fibres may underlie some forms of hyperalgesia.
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