万有
主要从事疼痛与镇痛机理研究,以脊髓背角和背根神经节为主要对象,研究疼痛与镇痛(包括针刺镇痛)尤其是慢性痛的神经生物学机制,涉及神经元与胶质细胞的离子通道、受体、信号转导等。
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- 姓名:万有
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学术头衔:
博士生导师
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学科领域:
神经生物学
- 研究兴趣:主要从事疼痛与镇痛机理研究,以脊髓背角和背根神经节为主要对象,研究疼痛与镇痛(包括针刺镇痛)尤其是慢性痛的神经生物学机制,涉及神经元与胶质细胞的离子通道、受体、信号转导等。
万有教授,1963年11月生,博士生导师,基础医学院副院长,北京大学神经科学研究所常务副所长、教育部神经科学重点实验室主任、教育部“跨世纪优秀人才培养计划”获得者、人事部“新世纪百千万人才工程”国家级人选。接受过正规的学历教育。1985年和1990年于河南医科大学分别获医学学士学位和硕士学位,1993年于武汉同济医科大学获博士学位,1995年于北京医科大学博士后出站。1998年至2000年在美国NIH基金资助下先后在美国伊利诺伊州立大学新泽西州立大学做科研合作。博士后出站后留校任教至今,2001年破格晋升为教授,随即聘为博士生导师。目前任中国神经科学学会理事兼副秘书长、中华医学会疼痛分会委员兼学术秘书、北京神经科学学会理事兼秘书长、中国针灸学会针刺麻醉与针刺镇痛原理分会理事,国际疼痛学会会员、生理学会会员,国内《Neuroscience Bulletin》等四种学术刊物编委,国内外十余种专业学术刊物审稿人。主要从事疼痛与镇痛机理研究,以脊髓背角和背根神经节为主要对象,研究疼痛与镇痛(包括针刺镇痛)尤其是慢性痛的神经生物学机制,涉及神经元与胶质细胞的离子通道、受体、信号转导等。1997年以来先后负责十五项国家和省部级科研课题,参编书籍10余部,发表论文70余篇,包括SCI论文20篇。今年来的研究论文主要发表于国际SCI收录杂志。
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11
【期刊论文】The effect of genotype on sensitivity to electroacupuncture analgesia
万有, You Wan a, b, Sony a G. Wilson b, Ji-Sheng Han a, Jeffrey S. Mogil b, *
Pain 91(2001)5-3,-0001,():
-1年11月30日
Individual differences in sensitivity to pain and analgesia are well appreciated, and increasing evidence has pointed towards a role of inherited genetic factors in explaining some proportion of such variability. It has long been known by practitioners of acupuncture, an ancient modality of analgesia, that some patients are responders' and others `non-responders.' The present research was aimed at de
Antinociception, Pain, Acupuncture, Mice, Inbred strains, Genetic
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万有, Qian Sun, Guo-Gang Xing, Hui-Yin Tu, Ji-Sheng Han, You Wan*
Brain Research 1032(2005)63-69,-0001,():
-1年11月30日
Peripheral nerve injury causes ectopic discharges of different firing patterns, which may play an important role in the development of neuropathic pain. The molecular mechanisms underlying the generation of ectopic discharges are still unclear. In the present study, by using in vivo teased fiber recording technique we examined the effect of ZD7288, a specific blocker of hyperpolarization-activated current (Ih), onthe ectopic discharges in the dorsal root ganglion (DRG) neurons injured by spinal nerve ligation. We found that ectopic discharges of all three firing patterns (tonic, bursting and irregular) were dose- and time-dependently inhibited by local application of ZD7288. Interestingly, the extent of suppression was negatively related to frequency of firing prior to application of ZD7288. We also observed that ZD7288 could alter the firing patterns of the ectopic discharges. At 100AM, tonic firing pattern was gradually transformed into bursting type whereas at 1 mM, it could be transformed to integer multiples firing. These results indicate that Ih might play a role in the generation of various forms of ectopic discharges in the injured DRG neurons and may thus be a possible target for neuropathic pain treatment.
Neuropathic pain, Ectopic discharge, Ih, HCN channel, ZD7288, Teased fiber recording
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万有, Xiao-Qing Tang, Yun Wang, Zhi-Hua Huang, Ji-Sheng Han and You Wan
Vol. 15 No.31 March 2004,-0001,():
-1年11月30日
The aim of the present study was to assess the e
Adenovirus, Corticospinalmotoneuron, GDNF, Gene therapy, Spinal cord injury
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万有, Huiyin Tu, Lunbin Deng, Qian Sun, Lei Yao, Ji-Sheng Han, and You Wan*
Journal of Neuroscience Research 76: 713-722 (2004),-0001,():
-1年11月30日
The large, medium-sized, and small neurons of the dorsal root ganglion (DRG) have different functions in the processing of various senses. Hyperpolarization-activated, cyclic nucleotide-gated channels (HCN) contribute greatly to neuronal excitability. In the present study, which used whole-cell patch clamp techniques and immunohistochemical staining methods, the electrophysiological properties of DRG neurons were systematically compared, and the roles of HCN-1, -2, and -4 were examined. The main results were as follows. 1) The large neurons had significantly higher V0.5 values (membranepotential at which the HCN channels were half-activated) and shorter time constants (HCN) than small or mediumsized DRG neurons. However, large DRG neurons had higher Ih density (HCN neuron current). 2) HCN-1 was found predominantly, but not exclusively, in large and medium-sized DRG neurons; HCN-2 was found in all DRG neurons; and HCN-4 was poorly visualized in all DRG neurons. HCN-1 and HCN-2 were colocalized in large and medium-sized neurons with immunostaining of adjacent sections. In the dorsal horn of the spinal cord, HCN-1, HCN-2, and HCN-4 were all expressed in laminae I-IV, although HCN-1 was not detectable in lamina II. 3) Blockade of Ih current in DRG neurons caused a signi ficant decrease in V0.5, resting membrane potential, and repetitive firing number of action potential and a significant increase in time of rising phase of action potential. These results suggest that the different HCN channels in the three types of DRG neurons might contribute to their differential electrophysiological properties.
hyperpolarization-activated, cyclic nucleotidegated channel, Ih, dorsal root ganglion, ZD7288
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万有, Hao Luo, Jin Cheng, Ji-Sheng Han and You WanCA
Vol. 15 No.4 22 March 2004,-0001,():
-1年11月30日
The present study aimed to systematically observe the change of vanilloidreceptor1 (VR1) during in
Complete Freund', s adjuvant, Dorsal root ganglion, In
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万有, Cheng Huang, Yun Wang, Ji-Sheng Han, You Wan*
Brain Research 945(2002)20-25,-0001,():
-1年11月30日
The present study was conducted to evaluate the characteristics of electroacupuncture (EA)-induced analgesia in mice. Three inbred strains of mice (DBA/2, C57BL/6J, BALB/c) and three outbred strains (ICR, LACA, NIH) were used in the experiment. Two pairs of metallic needles were inserted into acupoints ST 36 and SP 6 connected to an electric pulse generator. EA parameters were set as constant current output with alteration of a positive and negative square wave, 0.6ms in pulse width for 2Hz and 0.3ms for 100Hz. Tail-flick latencies evoked by radiant heat were measured before, during and after EA stimulation. We found that (1) DBA/2 mice showed a significantly more potent analgesic effect than the other five strains in response to both 100 and 2Hz EA. In this case, the intensities were 1.0-2.0-2.0mA, 10 min for each intensity totally 30min. (2) EA analgesia increased as the intensity of stimulation increased from 0.5 to 21 2.0mA, but it remained at this plateau when the intensity further increased from 2.0 to 3.0mA. (3) 10.0mg?kg naloxone was needed to 21 block the analgesic effect induced by 2Hz EA of 2.0mA, but to block that by 100Hz, 25.0mg?kg was necessary. (4) A positive 21 correlation was observed between analgesia induced by morphine at the dose of 5.0mg?kg and by 100Hz EA in two tested strains DBA/2 and C57BL/6J. In conclusion, EA induces reliable, strain-dependent analgesia in mice. The naloxone-reversibility of EA, a measure of whether it is opioid or non-opioid mediated, is dependent upon intensity and frequency.
Analgesia, Electroacupuncture, Strain, Morphine, Naloxone
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【期刊论文】Adenovirus-mediated GDNF protects cultured motoneurons from glutamate injury
万有, Xiao-Qing Tang, Yun Wang, Ji-Sheng Han and You WanCA
Vol. 12 No.14 8 October 2001,-0001,():
-1年11月30日
The protective effects of adenovirus-mediated glia cell linederived neurotrophic factor (GDNF) gene transaction was investigated on cultured motoneurons. First, the dose
Adenovirus, Excitatory amino acid, Gene therapy, Glia cell line-derived neurotrophic factor, Glutamate, Motoneuron, Spinal cord
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万有, Qian Sun, Huiyin Tu, Guo-Gang Xing, Ji-Sheng Han, You Wan*
Experimental Neurology 191(2005)128-136,-0001,():
-1年11月30日
It is widely accepted that ectopic discharges originated from injured sites and dorsal root ganglion (DRG) neurons after peripheral nerve injury contribute to neuropathic pain. However, it has been recently shown that ectopic discharges were not always necessary for neuropathic pain. In the present study, we aim to further examine the role of ectopic discharges in neuropathic pain in a spinal nerve ligation (SNL) model. With teased fiber recordings in vivo, the characteristics of ectopic discharges were observed over 14 days after SNL, and the correlation between ectopic discharges and tactile allodynia was analyzed. It was observed that ectopic discharges have three firing patterns (tonic, bursting, and irregular) after SNL, and proportions of these three patterns changed dynamically over time. The tonic and bursting types were dominant in the first 24h following SNL, while the irregular type became the only pattern in the late stage (day14). The average frequencies of ectopic discharges and the percentage of active filaments also changed over time, reaching the peak 24h after SNL and then declined gradually. Ectopic discharges were highly correlated with tactile allodynia in the first 24h following SNL, but surprisingly, not in the late stage of days 1 to 14. These findings suggest that ectopic discharges may be crucial in the triggering of neuropathic pain in the early stage, but their importance become more limited over time.
Ectopic discharge, Dorsal root ganglion, Neuropathic pain, Spinal nerve ligation, Teased fiber recording, Tactile allodynia
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万有, Cheng Huang a, b, Hua Long a, Yu-Shun Shi a, Ji-Sheng Han a, You Wan a, *
Neuroscience Letters 375(2005)138-142,-0001,():
-1年11月30日
Our previous studies have shown that 100Hz electroacupuncture (EA) produced antinociception through the release of endogenous opioids (mainly dynorphin) and the activated -opioid receptors in normal rats. Acupuncture is an effective treatment in relieving pain, but it develops tolerance after epeated administration. It has been reported that N-methyl-d-aspartate (NMDA) receptor antagonists could increase the antinociceptive effects induced by morphine and delay the development of tolerance to morphine but nothing has yet been described to reduce EA tolerance. Here we test whether ketamine, a non-competitive NMDA receptor antagonist, would enhance 100Hz EA antinociception as well as prevent or delay the development of chronic tolerance to 100Hz EA in normal rats. The results are as follows: (1) ketamine injected intraperitoneally (i.p.) 15min prior to EA enhanced the antinociceptive effects of 100 Hz EA at a dose of 5.0mg/kg, but not 0.2 or 1.0mg/kg. However, ketamine at either dose did not affect the basal nociceptive threshold (represented by tail-flick latency). (2) Ketamine at a dose of 5.0mg/kg delayed the development of chronic tolerance to 100Hz EA antinociception. We conclude that ketamine can enhance antinociception of 100Hz EA and delay the tolerance to 100Hz EA in rats. These results suggest that the development of 100Hz EA tolerance to antinociception was mediated, at least in part, through peripheral NMDA receptors, which may be useful in improving the therapeutic effects of EA in the treatment of pain when EA tolerance occurs.
Electroacupuncture, Analgesia, Tolerance, Ketamine, NMDA receptor
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万有, Cheng Huang a, b, Han-Ting Li b, Yu-Shun Shi a, Ji-Sheng Han a, You Wan a, *
Neuroscience Letters 368(2004)327-331,-0001,():
-1年11月30日
Mu-opioid agonists and N-methyl-d-aspartate (NMDA) receptor antagonists have been shown to attenuate mechanical allodynia in neuropathic pain models. We have previously reported that 2Hz ectroacupuncture (EA) produced analgesia via releasing endogenous opioid peptides (i.e.-endorphin and endomorphin) and the activated-opioid receptors. The present study aimed to examine whether ketamine, an NMDAreceptor antagonist, can enhance the anti-allodynic effects induced by 2 HzEAin a rat model of neuropathic pain following spinal nerve ligation (SNL). The results are as follows: (1) EA itself or i.p. injection of ketamine reduced mechanical allodynia (i.e.increase in withdrawal threshold). (2) Although injection of ketamine at a low dose (1.0mg/kg) alone did not influence mechanical withdrawal threshold, combination of ketamine at this dose with EA produced more potent anti-allodynic effect than that induced by EA alone. (3) The anti-allodynic effect of EA combined with ketamine could be reversed by i.p. injection of naloxone (2.0mg/kg). These results suggested that ketamine potentiate the anti-allodynic of EA in rats with spinal nerve ligation, and endogenous opioid system is likely to be involved in this process.
Neuropathic pain, Allodynia, Ketamine, NMDA receptor, Electroacupuncture, Opioid peptide
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