Hjornevik Trine, Jacobsen Line M, Qu Hong, Bjaalie Jan G, Gjerstad Johannes, Willoch Frode
Centre for Molecular Biology and Neuroscience & Institute of Basic Medical Sciences, University of Oslo, Norway National Institute of Occupational Health, Norway Department of Molecular Biosciences, University of Oslo, Norway Department of Radiology, Aker University Hospital, Norway.
Pain. 2008 Dec;140(3):456-464. doi: 10.1016/j.pain.2008.09.029. Epub 2008 Nov 11.
It has been suggested that spinal cord long-term potentiation (LTP) may contribute to hypersensitivity and hyperalgesia. We have investigated if noxious stimulus-induced spinal cord LTP might have a long lasting effect on supraspinal neuronal activity. First, we verified that spinal LTP was induced by electrical high frequency stimuli (HFS) conditioning applied to the sciatic nerve. The C-fibre response in the dorsal horn reached a twofold increase 150 min after HFS (t-test, p<0.01, n=6). Then, to study the metabolic supraspinal activity following the same stimulation protocol, we used small animal positron emission tomography (PET) and the glucose analog [(18)F]-fluorodeoxyglucose (FDG). With this combined approach we measured changes in regional supraspinal activity at two time points in HFS conditioned and in sham animals; acute (immediately after HFS/sham, n=4) and late phase (150 min after HFS/sham, n=10). Comparisons between HFS and sham groups revealed that induction of spinal LTP was followed by an acute metabolic response in the primary somatosensory cortex (S1), but also various slower metabolic adaptations in brain regions involved in modulation of nociceptive signaling and descending inhibition, i.e., amygdala, periaqueductal gray (PAG), rostral ventromedial medulla (RVM), and the dorsolateral pontomesencephalic tegmentum (DLPT) (t-test, p<0.05). The study demonstrates that PET may be used as an in vivo method to study regional brain metabolic activity between different conditions. It is concluded that noxious sciatic stimuli which induce spinal cord LTP also affect supraspinal metabolic activity. We suggest that these changes might illustrate a supraspinal maladaptive dysfunction involved in pain hypersensitivity and hyperalgesia.
有人提出脊髓长时程增强（LTP）可能导致超敏反应和痛觉过敏。我们研究了伤害性刺激诱导的脊髓LTP是否可能对脊髓上神经元活动产生持久影响。首先，我们验证了通过对坐骨神经施加高频电刺激（HFS）条件刺激可诱导脊髓LTP。高频刺激后150分钟，背角中的C纤维反应增加了两倍（t检验，p<0.01，n = 6）。然后，为了研究在相同刺激方案后的脊髓上代谢活动，我们使用了小动物正电子发射断层扫描（PET）和葡萄糖类似物[（18）F] - 氟脱氧葡萄糖（FDG）。通过这种联合方法，我们在HFS条件刺激组和假手术动物的两个时间点测量了脊髓上区域活动的变化；急性（HFS/假手术后立即，n = 4）和晚期（HFS/假手术后150分钟，n = 10）。HFS组和假手术组之间的比较显示，脊髓LTP的诱导伴随着初级体感皮层（S1）的急性代谢反应，但在参与伤害性信号调制和下行抑制的脑区，即杏仁核、导水管周围灰质（PAG）、延髓头端腹内侧网状结构（RVM）和背外侧脑桥中脑被盖（DLPT）也有各种较慢的代谢适应（t检验，p<0.05）。该研究表明PET可作为一种体内方法来研究不同条件下的脑区代谢活动。得出的结论是，诱导脊髓LTP的伤害性坐骨神经刺激也会影响脊髓上代谢活动。我们认为这些变化可能说明了参与疼痛超敏反应和痛觉过敏的脊髓上适应不良性功能障碍。
