刘先国
从事病理性疼痛的中枢和外周机制的研究
个性化签名
- 姓名:刘先国
- 目前身份:
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学术头衔:
博士生导师
- 职称:-
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学科领域:
无线电物理
- 研究兴趣:从事病理性疼痛的中枢和外周机制的研究
刘先国教授,1957年出生于内蒙古,1992年~1999年先后在德国海得堡大学生理研究所和德国基尔大学研究所攻读博士学位和做博士后。1999年5月被原中山医科大学作为学科带头人引进加回国,任教授、博士生导师、现任生理教研室主任、中山大学基础医学院副院长、兼任广东省生理学会理事长、广东省医学会疼痛分会常委、中国生理学会理事及神经科学专业委员会委员、《生理学报》编委会委员等。在国内外发表研究论文30余篇,SCI收录15篇。长期从事病理性疼痛的中枢和外周机制的研究。主要研究包括:
(1)首次报道了脊髓背角C纤维诱发电位的长时程增强(LTP)。发现激动NMDA、NK1和NK2受体是诱导LTP的必要条件;自然痛刺激可引起C纤维诱发电位的LTP,但在正常情况下受到下行抑制系统的抑制。该LTP被认为是痛觉过敏的基础; 发现脊髓LTP的早期维持与PKA、PKC和CaMKII的激活有关,而脊髓LTP的晚期需要新的蛋白质合成;多巴胺D1/D5受体在LTP的晚期维持中起重要作用。
(2)发现电刺激Aδ纤维在正常动物引起C纤维诱发电位的LTD, 然而同样的刺激在脊动物引起LTP, 证实下行抑制系统决定脊髓背角突触传递可塑性变化的方向。
(3)率先证实,神经损伤引起的背根神经节神经元的异常放电主要来自于支配肌肉的神经元。在神经损伤的情况下,未被损伤的神经元也产生异常放电。2004年主编了《生理学》,由科学出版社出版。
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成果数
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【期刊论文】磷酸化钙/钙调蛋白依赖性蛋白激酶Ⅱ在大鼠脊髓背角C-纤维诱发电位长时程增强的诱导和维持中的作用
刘先国, 信文君, 黎明涛, 杨红卫, 张红梅, *, 胡能伟, 胡晓东, 张彤
生理学报,2004,56(1):83~88,-0001,():
-1年11月30日
实验旨在探讨钙/钙调蛋白依赖性蛋白激酶Ⅱ(calcium/calmodulin-dependentprotein kinase Ⅱ,CaMKII)在脊髓背C-纤维诱发电位长时程增强(long-term potentiation,LTP)的诱导和维持中的作用。用western blot技术分别检测LTP形成30min和3h脊髓背角(L4-L6)CaMKⅡ的含量及其磷酸化水平。同时观察脊髓局部给予CaMKⅡ选择性抑制剂KN-93后对脊髓背角LTP和CaMKⅡ磷酸化的影响。观察结果如下:(1)诱导LTP后30min,CaMKⅡ的磷酸化水平明显高于对照组,而CaMKⅡ的总量无变化;诱导LTP后3h CaMKⅡ的磷酸化水平进一步升高,而且CaMKⅡ的总量也叫显增力(n=4);(2)强直刺激前30min于脊髓局部给予CaMKⅡ的特异性抑制剂KN-93(100μmol/L),可阻断LTP的诱导,同时明显抑制CaMKⅡ的磷酸化水平;(3)诱导LTP后30min给予KN-93,可显著抑制LTP的维持,同时CaMKII的磷酸化水平与未用药组相比也明显降低(n=3);(4)LTP3h后给予KN-93,LTP的幅值不受影响,磷酸化的CaMKⅡ的含量与用药前相比也无差别(n=3)。根据卜述实验结果可以认为,CaMKⅡ的激活参与脊髓背角C-纤维诱发电化LTP的诱导和早期维持过程。
钙/, 钙调蛋白依赖性蛋白激酶Ⅱ(, CaMKⅡ), , KN-93, 电位长时程增强(, LTP), , 脊髓背角, 蛋白质印迹(, westemblot),
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刘先国, Hong-Wei Yang, Xiao-Dong Hu, Hong-Mei Zhang, Wen-Jun Xin, Ming-Tao Li, Tong Zhang, Li-Jun Zhou, and Xian-Guo Liu
Neurophysiol 91: 1122-1133, 2004.,-0001,():
-1年11月30日
Long-term potentiation (LTP) of C-fiber-evoked field potentials in spinal dorsal horn may be relevant to hyperalgesia, an increased response to noxious stimulation. The mechanism underlying this form of synaptic plasticity is, however, still unclear. Considerable evidence has shown that calcium/calmodulin-dependent protein kinase II (CaMKII), protein kinase A (PKA), and protein kinase C (PKC) are important for LTP in hippocampus. In this study, the roles of these three protein kinases in the induction and maintenance of LTP of C-fiber-evoked field potentials were evaluated by application of specific inhibitors of CaMKII (KN-93 and AIP), PKA (Rp-CPT-cAMPS), and PKC (chelerythrine and Go6983) at the recording segments before and after LTP induction in urethaneanesthetized Sprague-Dawley rats. We found both KN-93 and AIP, when applied at 30min prior to tetanic stimulation, completely blocked LTP induction. At 30min after LTP induction, KN-93 and AIP reversed LTP completely, and at 60min after LTP induction, they depressed spinal LTP in most rats tested. Three hours after LTP induction, however, KN-93 or AIP did not affect the spinal LTP. Rp-CPT-cAMPS, chelerythrine, and Go 6983 blocked the spinal LTP when applied at 30min before tetanic stimulation and reversed LTP completely at 15min after LTP induction. In contrast, at 30min after LTP induction, the drugs never affected the spinal LTP. These results suggest that activation of CaMKII, PKA, and PKC may be crucial for the induction and the early-phase but not for the late-phase maintenance of the spinal LTP.
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刘先国, H.-J. Ha
Pain 87(2000)335-345,-0001,():
-1年11月30日
Transection of the L5 spinal nerve in rats results in allodynia- and hyperalgesia-like behavior to mechanical stimulation which are thought to be mediated by ectopic activity arising in lesioned afferent neurons mainly in the dorsal root ganglion (DRG). It has been suggested that the neuropathic pain behavior is dependent on the sympathetic nervous system. In rats 3
Neuropathic pain, L5 spinal nerve injury, Sympathetically maintained pain, Dorsal root ganglion, Neurogenic vasoconstriction, Sympathetic nervous system
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【期刊论文】Spontaneous activity of axotomized afferent neurons after L5 spinal nerve injury in rats
刘先国, Xianguo Liu, Sebastian Eschenfelder, Karl-Heinz Blenk, Wilfrid Ja
Pain 84(2000)309-318,-0001,():
-1年11月30日
After mechanical injury of a peripheral nerve some axotomized afferent neurons develop spontaneous activity, which is thought to trigger abnormal pain behavior in rats and neuropathic pain in humans. Here, we analysed the ectopic activity in axotomized afferent fibers recorded from the L5 dorsal root in different time periods after L5 spinal nerve lesion and the effects of sympathectomy on it. The following results were obtained: (1) Up to 6 hours after spinal nerve transection there was almost no spontaneous activity in axotomized afferents, except short-lasting injury discharges at the time of transection; (2) Three to 8 days following spinal nerve lesion, the rate of spontaneous activity was 7:3
Neuropathic pain, Allodynia, L5 spinal nerve lesion, Ectopic activity, Sympathetically maintained pain, Sympathectomy
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刘先国, Jurgen Sand kuhler and Xianguo Liu
European Journal of Neuroscience, 10, 2476-2480,-0001,():
-1年11月30日
Use-dependent long-term potentiation of synaptic strength (LTP) is an intensively studied model for learning and memory in vertebrates. Induction of LTP critically depends on the stimulation parameters of presynaptic fibres with synchronous high-frequency bursts being most effective at many central synapses. It is, however, not known whether naturally occurring discharge patterns may induce LTP and whether LTP has any biological function in sensory systems. Here we have investigated the LTP of excitatory synaptic transmission between primary afferent C-fibres, many of which are nociceptors, and neurons in rat superficial spinal dorsal horn. LTP that lasted for 4-6 h could not only be induced by electrical stimulation of sural nerve but also by natural stimulation of heat-, mechano- or chemosensitive nociceptors in the skin or by acute nerve injury. Maintenance of LTP was not affected when afferent nerves were cut 1h or 5min after noxious skin stimulation, indicating that an ongoing afferent barrage is not required. Natural noxious stimuli induced LTP in animals which were spinalized but were ineffective in intact animals. Thus, induction of LTP is suppressed by tonically active supraspinal descending systems. We conclude that the natural non-synchronized discharge patterns that are evoked by noxious stimulation may induce LTP and that this new form of LTP may be an underlying mechanism of afferent induced hyperalgesia.
hyperalgesia,, LTP,, pain,, rat,, sensory stimulation,, synaptic plasticity
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刘先国, Neng-Wei Hu, Hong-Mei Zhang, Xiao-Dong Hu, Ming-Tao Li, Tong Zhang, Li-Jun Zhou, and Xian-Guo Liu
J Neurophysiol 89: 2354-2359, 2003,-0001,():
-1年11月30日
Previous studies have demonstrated that in the hippocampus the maintenance of long-term potentiation (LTP) requires de novo protein synthesis. To investigate the role of protein synthesis in the maintenance of LTP of C-fiber evoked field potentials in spinal dorsal horn, which may be relevant to hyperalgesia, protein synthesis inhibitor (either cycloheximide or anisomycin) was applied locally to the recording segments of spinal cord in anesthetized rats, 30 min prior to tetanic stimulation to the sciatic nerve. We found that both cycloheximide and anisomycin selectively inhibited late-phase maintenance of the spinal LTP but affected neither LTP induction nor baseline responses of C-fiber evoked field potentials. In the presence of cycloheximide, LTP of C-fiber evoked field potentials was 281.5
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刘先国, X.-G. LIU and J. SANDKOHLER *
Neuroscience Vol. 68, No.4, pp. 1207-1218, 1995,-0001,():
-1年11月30日
Inflammation of the skin induces release and extrasynaptic spread of neuropeptides such as substance P mainly in spinal laminae I and II and causes changes in discharge properties of nociceptive neurons in spinal dorsal horn. To evaluate the role of extrasynaptic substance P we have superfused the spinal cord at recording segment with artificial cerebrospinal fluid or with substance P. A total of 102 multireceptive neurons responding to both noxious and innocuous skin stimulation were recorded in laminae I or II of lumbar spinal dorsal horn in pentobarbital anaesthetized rats. During superfusion with substance P (10 or 100pM) significant increases of background activities (from 2.2
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刘先国, Hong-Mei Zhang, Ying-Jie Qi, Xu-Ying Xiang, Tong Zhang, Xian-Guo Liu *
Neuroscience Letters 315(2001)81-84,-0001,():
-1年11月30日
Our previous work has shown that repetitive stimulation of Ad-fibers depresses long-term potentiation (LTP) of C-fiber evoked field potentials in spinal dorsal horn. Here, we tested the effects of the Ad stimulation on the spinal LTP at different time points following LTP induction. Fifteen minutes after LTP induction Ad stimulation depressed LTP by 44.1
Long-term potentiation, Long-term depression, Spinal dorsal horn, C-fiber, Nociception, Ad-fiber
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刘先国, J. SANDKUHLER, *, A.-C. TREIER, X.-G. LIU and M. OHNIMUS
Neuroscience Vol. 73, No.3, pp. 657-666, 1996,-0001,():
-1年11月30日
It has been suggested that the expression of c-fos and other immediate early genes in spinal dorsal horn neurons would trigger changes in the phenotype of nociceptive neurons which may lead to long-term changes in spinal nociception. To test this hypothesis, we have used a minimally invasive intrathecal stimulation and injection technique which can be applied to adult Sprague-Dawley rats under brief ether anesthesia to induce massive c-fos expression in spinal neurons without affecting peripheral nociceptors. Electrical intrathecal stimulation (0.5ms pulses, 15V, 3Hz for 15 rain) or intrathecal injection of N-methyl-D-aspartate (25nmol) produced massive c-Fos immunoreactivity in neurons throughout the sacral spinal cord and the dorsal horn of the lumber spinal cord. Immunoreactivity declined to control values at mid-thoracic levels. To assess effects of these intrathecal stimuli on nociception, hot-plate and tail-flick latencies and mechanical thresholds of hindlimb withdrawal reflexes were measured once every day for 14 days before and up to 14 days after conditioning stimulation. Spontaneous locomotion of each animal was video-taped daily for 5 min and analysed off-line. On the day of the intrathecal stimulation the tests were performed 1 h before and also 6 h after conditioning stimulation. Thermal and mechanical nociceptive thresholds were temporarily enhanced 6 h after intrathecal stimulation but they were not different from controls one to 14 days later. Thus, the massive expression of c-fos in spinal neurons is not, as previously suggested, a sufficient condition for the induction of long-term changes in spinal nociception. Copyright
spinal dorsal horn,, pain,, thermal hyperalgesia,, mechanical hyperalgesia,, immediate early gene,, long-term depression,, rat.,
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