Perceptual correlates of nociceptive long-term potentiation and long-term depression in humans
Perceptual correlates of nociceptive long-term potentiation and long-term depression in humans
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DOI：
10.1523/jneurosci.1222-03.2004
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发表时间：
2004-01-28
影响因子：
5.3
通讯作者：
Treede, RD
中科院分区：
文献类型：
--
作者：
Klein, T;Magerl, W;Treede, RD
突触强度的长时程增强（LTP）和长时程抑制（LTD）是突触可塑性的普遍机制，但它们在人类中的功能相关性仍然不清楚。在这里，我们报告了对电测试刺激的感知疼痛的长期增加是由肽能皮肤传入的高频电刺激（HFS）（100 Hz下5 X 1秒）诱导的（高于基线27%，>3小时未减弱）。相比之下，低频刺激（LFS）（1Hz下17分钟）可诱导感知疼痛的长期降低（低于基线27%，持续1小时未减弱）。在邻近HFS-LFS调节皮肤部位的皮肤中用点状机械探针（直径200 μ m）进行的疼痛测试显示，HFS后疼痛敏感性（继发性痛觉过敏，>3小时不减弱）显著增加两倍至三倍，但在强LFS后也有中度继发性痛觉过敏（高于基线30%）。此外，HFS而不是LFS引起邻近皮肤的轻微触觉刺激疼痛（异常性疼痛）。总之，在动物实验中，在脊髓伤害性通路中诱导LTP或LTD的HFS和LFS刺激方案导致由条件通路介导的人类疼痛感知的类似LTP和LTD样变化（长期痛觉过敏或痛觉减退）。此外，继发性痛觉过敏和异常性疼痛在相邻的皮肤引起的HFS协议，并在较小程度上，也由LFS协议，表明这些感知的变化包括LTP样的异突触促进相邻的伤害性通路的一个迄今为止未知的机制。
Long-term potentiation (LTP) and long-term depression (LTD) of synaptic strength are ubiquitous mechanisms of synaptic plasticity, but their functional relevance in humans remains obscure. Here we report that a long-term increase in perceived pain to electrical test stimuli was induced by high-frequency electrical stimulation (HFS) (5 X 1 sec at 100 Hz) of peptidergic cutaneous afferents (27% above baseline, undiminished for >3 hr). In contrast, a long-term decrease in perceived pain (27% below baseline, undiminished for 1 hr) was induced by low-frequency stimulation (LFS) (17 min at 1 Hz). Pain testing with punctate mechanical probes (200 mum diameter) in skin adjacent to the HFS-LFS conditioning skin site revealed a marked twofold to threefold increase in pain sensitivity (secondary hyperalgesia, undiminished for >3 hr) after HFS but also a moderate secondary hyperalgesia (30% above baseline) after strong LFS. Additionally, HFS but not LFS caused pain to light tactile stimuli in adjacent skin (allodynia). In summary, HFS and LFS stimulus protocols that induce LTP or LTD in spinal nociceptive pathways in animal experiments led to similar LTP- and LTD-like changes in human pain perception (long-term hyperalgesia or hypoalgesia) mediated by the conditioned pathway. Additionally, secondary hyperalgesia and allodynia in adjacent skin induced by the HFS protocol and, to a minor extent, also by the LFS protocol, suggested that these perceptual changes encompassed an LTP-like heterosynaptic facilitation of adjacent nociceptive pathways by a hitherto unknown mechanism.