Spinal long-term potentiation is associated with reduced opioid neurotransmission in the rat brain
Spinal long-term potentiation is associated with reduced opioid neurotransmission in the rat brain
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DOI：
10.1111/j.1475-097x.2010.00939.x
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发表时间：
2010-07-01
影响因子：
1.8
通讯作者：
Willoch, Frode
中科院分区：
文献类型：
--
作者：
Hjornevik, Trine;Schoultz, Bent W.;Willoch, Frode
前言：伤害性痛觉通路中导致长时程增强（LTP）的神经元事件可能是痛觉过敏的细胞机制。在本研究中，我们研究是否诱导脊髓LTP可能与脊髓上阿片系统的功能变化。方法：采用高频电刺激（HFS）条件性刺激坐骨神经诱发脊髓LTP，并通过脊髓场电位记录证实脊髓水平的兴奋性。为了研究相同HFS条件下阿片类神经传递的脊髓上变化，我们使用小动物正电子发射断层扫描（PET）和[11 C]苯乙基-奥维醇（[11 C]PEO）。结果：在HFS预处理后150 min，观察到明显的C-纤维LTP，即C-纤维反应增强和C-纤维阈值降低（t检验，P < 0，中心点05，n = 6）。此外，在同侧杏仁核、海马、躯体感觉皮层和上级丘以及双侧延髓核、尾壳核和下丘脑中，在相同类型的HFS条件化后，观察到OR结合相对于基线增加（配对t检验，HFS >基线，P < 0，中心点05，n = 8）。坐骨神经的HFS调节导致脊髓LTP和脊髓上阿片样物质信号传导的功能变化。我们的研究结果表明，脊髓LTP的诱导可能与疼痛调制和情感情绪反应相关的脑区阿片类神经传递减少有关。
P>Introduction:Neuronal events leading to development of long-term potentiation (LTP) in the nociceptive pathways may be a cellular mechanism underlying hyperalgesia. In the present study, we examine if induction of spinal LTP may be associated with functional changes in the supraspinal opioidergic system. The opioid receptors (ORs) play a key role in nociceptive processing and controlling the descending modulatory system to the spinal cord.Methods:Spinal LTP was induced by electrical high-frequency stimulation (HFS) conditioning applied to the sciatic nerve, and the excitability at spinal level was verified by spinal field potential recordings. To study supraspinal changes in opioid neurotransmission following the same HFS conditioning, we used small animal positron emission tomography (PET) and [11C]Phenethyl-Orvinol ([11C]PEO). All rats included in the PET study were scanned at baseline and 150 min after HFS, and specific binding was calculated with a reference tissue model.Results:A clear C-fibre LTP, i.e. increased C-fibre response and reduced C-fibre threshold, was observed 150 min after HFS conditioning (t-test, P < 0 center dot 05, n = 6). Moreover, increased OR binding, relative to baseline, was observed after the same type of HFS conditioning ipsilaterally in the amygdala, hippocampus, somatosensory cortex and superior colliculus, and bilaterally in the nucleus accumbens, caudate putamen and hypothalamus (paired t-test, HFS > baseline, P < 0 center dot 05, n = 8).Conclusions:HFS conditioning of the sciatic nerve resulted in both spinal LTP and functional changes in supraspinal opioidergic signalling. Our findings suggest that induction of spinal LTP may be associated with reduced opioid neurotransmission in brain regions involved in pain modulation and affective-emotional responses.