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Activation of p38/MAPK in the anterior cingulate cortex contributes to pain-related negative emotion in rats

Activation of p38/MAPK in the anterior cingulate cortex cont...

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中国生理学会第23届全国会员代表大会暨生理学学术大会

作者： Hong CAO~(1,2),Gen-Cheng WU~2,Zhi-Qi ZHAO~1,Yu-Qiu ZHANG~1 1 Institute of neurobiology 2 department of integrative medicine and neurobiology,institutes of brain research and state key laboratory of medical neurobiology shanghai medical college,fudan university,shanghai 200032,china

＜正＞Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, including a sensory-discriminative and an emotional-affective *** evidence from morphological, electrophysiological,neuroimaging,and behavioral studies as well as early clinical observation indicates that the anterior cingulate cortex（ACC） is involved in pain-related ***,little is known about the molecular and cellular mechanisms underlying pain-related aversion in *** previous studies showed that NMDAR-dependent ERK signaling cascade in rat ACC contributes to pain *** the present study we observed the role of p38,another member of MAP（mitogen-activated protein） kinase family,in ACC in pain-related negative emotion using Western Blot and behavioral ***-plantar injection of 5%formalin produced a robust increase in phosphorylated MKK3/6（pMKK3/6）,upstream of p38/MAPK,and phosphorylated p38（p-p38） in the bilateral rostral ACC（rACC）.Using formalin-induced conditioned place avoidance（F-CPA） in rats,which is believed to reflect the pain-related negative emotion,we found that blockade of p38/MAPK activation in the rACC with p38 inhibitor SB203580（0.1μg,1μg per side） but not low dose（0.01μg per side）,or another kind of p38 inhibitor SB239063（0.1μg,1μg per side） dose-dependently prevented the induction of ***,these blockades affected neither formalin-induced two-phase spontaneous pain nor low-intensity electric foot shock-induced CPA *** together,these results indicate that activation of p38/MAPK contributes to pain-related negative emotion,which will provide new molecule mechanisms underlying pain affect and bring new treatments for relieving emotional pain-related disturbance.

关键词： p38/MAPK formalin-induced conditioned place avoidance pain-related negative emotion anterior cingulate cortex rat

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Anti-allodynic effects of intrathcal lipoxins and analogs in rats with tibia bone cancer pain

Anti-allodynic effects of intrathcal lipoxins and analogs in...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Shan HU,Qi-Liang MAO-YING,Yan-Qing WANG~* department of integrative medicine and neurobiology,shanghai medical college,Institute of Acupuncture research, institutes of brain Science,state key laboratory of medical neurobiology,fudan university,shanghai 200032,china

＜正＞Objective Lipoxins represent a unique class of lipid mediators that can function as "braking signals" in *** A4（LXA4） and LXB4 are positional *** addition,a synthetic analogue of ATL（aspirintriggered lipoxin） has the same anti-inflammatory activities as the endogenous lipoxins and is more resistant to metabolic *** has been reported that both Lipoxins and aspirin-triggered lipoxins can inhibit inflammation *** bone cancer pain,many researches have indicated that the neuroinflammation involved in the pain processing. In this article,we performed a series of studies on the role of ATL in bone cancer *** Female SD rats （160-180 g） were used to establish the model of bone cancer pain by percutaneous direct puncture technique and inoculating the Walker256 mammary gland carcinoma cells into right tibial medullary cavity *** mechanic allodynia of rats were evaluated by von Frey hair and we gave the drugs by intrathecal ***（1） Compared to the vehicle-treated animals,intrathecal LXA4,LXB4 and ATL can up-regulate mechanical threshold;（2） ATL has a longer anti-allodynic effect than the other lipoxin *** Both Lipoxins and the analogy of lipoxins have anti-allodynic effects in tibial bone cancer ***,the molecular mechanism of lipoxins in bone cancer pain is still unclear and need to be further studied.

关键词： lipoxins aspirin-triggered lipoxin allodynia bone cancer pain

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Behavioral changes induced by Escitalopram treatment in helpless rats

Behavioral changes induced by Escitalopram treatment in help...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Bing LI~1,Na YUE~1,Qiong LIU~2,Yang LIU~1,Jin YU~1,Gen-Cheng WU~(1,3,*) 1 department of integrative medicine and neurobiology,state key lab of medical neurobiology,shanghai medical college,fudan university,shanghai 200032,china 2 department of Anatomy,Histology and Embryology,shanghai medical college,fudan university,shanghai 200032, china 3 institutes of brain science,fudan university,shanghai 200032,china

＜正＞Objective Depression is a severe illness and the prevalence increased gradually in the past decades according to large epidemiological ***,it is crucial to prevent the onset of the disease and approach effective *** aim of the present study was to examine whether Escitalopram treatment can cause antidepressant-like effect and behavior changes in helpless rats,rat models of *** 76 male SD rats were randomly divided into 5 groups:normal（n = 11）,model（n = 11）,depression + Saline（n = 10）,depression + Escitalopram（n = 8）,and depression + Clomipramine（as positive control,n = 11）.On 2 consecutive days,rats were exposed to 60 inescapable electric foot-shocks（IS）.Escape-avoidance behavior was evaluated 3 days after *** that failed to escape between 10 and 30 trials were considered "helpless".Then Escitalopram and Clomipramine treatments were given to helpless rats twice daily（intraperitoneal injection） at the dose of 10 mg/kg for 5 d starting on the evening of the third day after *** medication,the escape-avoidance behavior was evaluated *** depressive-like behaviors were evaluated before IS,after IS and treatment with drug in forced swimming and open field test through the *** As for the number of escape failures in the active avoidance task,the one-way ANOVA indicated a significant effect of treatment with escitalopram（F = 69.28,P＜0.01）.After inescapable footshock, helpless rats displayed significantly increased escape failure *** expected,helpless rats treated with escitalopram and clomipramine displayed decreased number of escape failures,as compared with helpless rats（F = 17.05,P＜0.01）. The open field test is a test of spontaneous motor activity for *** inescapable shook,the total distance of travel （F = 29.36,P＜0.01） of helpless rats was significantly decreased in the *** escitalopram and clomipramine treatment,the total distance of travel（F= 8.79,P＜0.01） of medication-treated rats si

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EA produces antidepressant effect by promoting the proliferation of both quiescent neural progenitors and amplifying neural progenitors in the dentate gyrus of hippocampus

EA produces antidepressant effect by promoting the prolifera...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Liu YANG~1,Qiong LIU~2,Bing LI~1,Na YUE~1,Jin YU~1,Gen-Cheng WU~(1,3,*) 1 department of integrative medicine and neurobiology,state key lab of medical neurobiology,shanghai medical college,fudan university,shanghai 200032,china 2 department of Anatomy,Histology and Embryology,shanghai medical college,fudan university,shanghai 200032, china 3 institutes of brain Science,fudan university,shanghai 200032,china

＜正＞In order to evaluate the antidepressant effect of electroacupuncture（EA） on the rat model of chronic unpredictable stress（CUS） and the proliferation promoting effect on stem / progenitor cells in the dentate gyrus （DG） of hippocampus,this study investigated the behavioral and brain section staining changes of 4 groups（normal, Model,Sham EA and EA）.After 2 weeks of CUS procedure,EA,as well as Sham EA,was performed on Du-20 （Bai-Hui） and GB-34（Yang-Ling-Quan） for 15 d（8 treatments in all）.Forced swimming test（FST）,elevated plus-maze （EPM） test and open field test（OFT） suggested that EA had reversed the depressive like ***, Sham EA,as designed on the real acupoints without electrical current,also showed a little antidepressant *** shown by 5-bromo-2-deoxyuridine（BrdU） and SOX-2 double-labeling immunofluorescence,proliferation of DG stem cells was decreased in model *** with the depression model,the decrease of stem-cell proliferation in both Sham EA and EA groups had begun to be significantly blocked since 2 treatments were carried *** the subpopulations of stem cells into consideration,we found that EA could up-regulate both quiescent neural progenitors （QNPs,SOX-2 positive and GFAP positive） and amplifying neural progenitors（ANPs,SOX-2 positive but GFAP negtive） in DG while Sham EA could only promote the latter,through SOX-2 and GFAP double *** further demonstrated that both Sham EA and EA increased p-ERK and SOX-2 double positive cells number and the both groups had the increasing effect at the same *** the EA group had a lower ratio of p-ERK in SOX-2 in respect that the total stem cell number was *** results suggest that EA has the antidepressant effect mediated by promoting both QNPs and ANPs in DG and that acupuncture could treat depression by activating ANPs,ERK as a possible passway to *** other passways may be included in the mechanism of EA antidepressant effect.

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Hypothalamic Medial Preoptic Area Mediates Electroacupuncture's Normalization of Hypothalamus-Pituitary- Ovary Axis Dysfunction

Hypothalamic Medial Preoptic Area Mediates Electroacupunctur...

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第十届全国针刺麻醉针刺镇痛及针刺调整效应学术研讨会

作者： Shulan Ma,Yi Feng,Boying Chen~*. Institute of Acupuncture research(WHO Collaborating Center for Traditional medicine),institutes of brain Science,department of integrative medicine and neurobiology,state key Lab of medical neurobiology,shanghai medical college, fudan university,shanghai,china.

We have previously reported that repeated treatments performed using electroacupuncture(EA) may normalize the dysfunction of the hypothalamus-pituitary-ovary axis(HPOA) in ovariectomized *** effect of EA treatment is seen in the hypothalamus,pituitary and peripheral tissue three levels in *** the primacy of the hypothalamic medial preoptic area(MPO) in the female reproductive system,we postulate that the MPO is the key site of action in EA treatment in female reproductive *** the first experiment,we used vaginal smear,circulating estrogen concentration and uterine morphology as indicators to validate the effects of EA on the HPOA dysfunction in ovariectomized ***,we adopted the push-pull perfusion method to detect the influence of EA on the release of gonadotropin releasing hormone(GnRH) decapeptide and neuroactive substances in the MPO of ovariectomized ***,a transfer of the MPO-perfusate from a donor ovariectomized rat that received EA treatment to the MPO of a recipient ovariectomized rat,similar EA effects could be induced in the *** results are the first to identify the MPO as a crucial site for EA treatment in normalizing reproductive dysfunction from *** may modulate the collaboration of inhibitory and stimulating factors on GnRH neurons in this region,thereby regulating the release of GnRH from the hypothalamus to facilitate the homeostasis of the *** article also provides a possibility that push-pull perfusate may be a promising method to explore the mechanism of EA in vitro.

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Inhibition of ERK activation decreases nociceptive behavior in rats of bone-cancer pain model

Inhibition of ERK activation decreases nociceptive behavior ...

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中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Xiao-Wei WANG,Qi-Liang Mao-YING,Yan-Qing WANG~*,Gen-Cheng WU~* department of integrative medicine and neurobiology,Institute of Acupuncture research,state key laboratory of medical neurobiology,shanghai medical college,fudan university,shanghai 200032,china

＜正＞Objective The mitogen-activated protein kinases（MAPK） transmit extracellular stimuli into intracellular transcriptional and post-translational *** in the intracellular signal transduction pathways（extracellular signal-regulated kinase（ERK）,p38 MAPK,c-Jun N-terminal kinase/stress-activated protein kinase（JNK/SAPK）） in spinal dorsal horn may contributes to pain *** pain is very common in patients with late stage cancer,and has the most significant impact on the life quality of patients,but the mechanism under this pain is not *** this study we investigated the role of the activation of ERK signaling pathway in bone cancer pain *** Bone cancer pain was induced in the right tibia of Wistar rats by injecting Walker 256 mammary gland carcinoma *** mechanical hyperalgesia was tested by Von Frey *** phosphorylation of ERK in spinal dosal horn was measured by immunohistochemistry and western ***（1） After the inoculation of tumor cells,ERK was activated in neurons,microglia and astrocytes.（2） Intrathecal infusion of PD98059（10μg）,an inhibitor of MEK（ERK kinase）,decreased the mechanical allodynia tested by Von Frey Hair in the bone-cancer pain *** These findings suggest that ERK play an important role in bone-cancer induced pain.

关键词： extracellular signal-regulated kinase(ERK) phosphorylation cancer pain

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Behavior changes after inescapable shocks

Behavior changes after inescapable shocks

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中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Bing LI,Qiong LIU,Xiao-Wei WANG,Yan-Qing WANG,Jin YU,Gen-Cheng WU~* department of integrative medicine and neurobiology,Institute of Acupuncture research,state key laboratory of medical neurobiology,institutes of brain Science,shanghai medical college,fudan university,shanghai,china

＜正＞Aim Inescapable shocks（IS） have been reported to cause various post-traumatic stress disorder（PTSD）-like behavioral changes in *** aim of the present study was therefore to examine whether IS can cause depressive and anxious behaviors in this *** Wister rats were tested the behaviors before inescapable foot-shocks（IS） or not shocked（non-S） in the Elevated Pluz Maze test on day ***,rats were given either IS or non-S treatment in a box on day 1 and day *** day 5,rats treated with IS and non-S were given an avoidance/escape test in the shuttle box and elevated pluz maze test *** In accordance with previously reported results,failures and escape latencies were taken as indicators for helplessness in avoidence/escape *** the IS-treated group,the number of failures and the latency to escape were increased at a significant level in the helplessed *** about 75%IS-treated rats were nonhelplessed. The number of failures and the latency to escape of the non-helplessed rats were not significantly different with non-IS ***,the helplessed rats spent less time in the open arms and increased time in the enclosed arms compared with non-helplesssed rats and non-IS *** The behavioral changes in helplessed rats after IS treatment is similar as the patients with *** learned helplessness will be helpful for performing the further research about the mechanism of PTSD.

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Robust spinal neuroinflammation mediates bilateral mechanical allodynia induced by intra-tibia inoculation of Walker 256 cancer cells in rats

Robust spinal neuroinflammation mediates bilateral mechanica...

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中国生理学会第23届全国会员代表大会暨生理学学术大会

作者： Qi-Liang MAO-YING,Xiao-Wei WANG,Xiu LI,Wen-Li MI,Gen-Cheng WU,Yan-Qing WANG department of integrative medicine and neurobiology,state key laboratory of medical neurobiology,institutes of brain Science, shanghai medical college,fudan university,shanghai 200032,china

＜正＞It has been reported that remarkable and sustained activation of spinal astrocyte and/or microglia induced by bone cancer pain in the animals,which were quite different from the neuropathic and inflammatory pain. The present study was designed to investigate the role of spinal Toll-like receptor 4（TLR4）-induced glial neuroinflammation,including the astrocyte and microglia activation,proinflammatory expression,in bone cancer pain in a modified rat *** results showed that,eight days after unilateral intra-tibial inoculation of syngeneic Walker 256 mammary gland carcinoma cells,a robust activation of both astrocyte and microglia in bilateral spinal dorsal horn,characterized by enhanced immunostaining of both glial fibrillary acidic protein（GFAP,astrocyte marker） and OX-42（microglia marker）,and elevated level of IL-1β,IL-6 and TNF-αmRNA,was observed as well as significant bilateral mechanical *** mechinacal allodynia and spinal neuroinflammation were sustained until 22 days after intra-tibial *** investigate the role of spinal astrocyte and microglia in the bone cancer pain,single dose of fluorocitrate（inhibitor of glial metabolism,1 nmol） or minocycline（inhibitor of microglia,100μg） were intra-thecal administered by lumbar puncture on day 12 after Walker 256 *** results showed that spinal administration of fluorocitrate or minocycline has significant anti-allodynic effects in this bone cancer pain rats,suggesting that spinal astrocyte and microglia were involved in the process of bone cancer *** has been reported that TLR4 is almost exclusively expressed by microglia and a very intriguing mechanism proposed for spinal microglial activation in response to peripheral nerve injury is activation of *** order to confirm whether TLR4 was involved in bone cancer pain,nonstereoselective TLR4 receptor antagonist naloxone（60μg,i.t.） was also intra-thecally *** result showed that it could significantly block the incre

关键词： bone cancer pain mechanical allodynia neuroinflammation Toll-like receptor 4 rat

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Electroacupuncture downregulates TLR2/4 and pro-inflammatory cytokine expression after surgical trauma stress without adrenal glands involvement

Electroacupuncture downregulates TLR2/4 and pro-inflammatory...

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中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Jun WANG,Jing LI,Yan-Qing WANG,Gen-Cheng WU~* department of integrative medicine and neurobiology,Institute of Acupuncture research WHO Collaborating Center for Traditional medicine,institutes of brain Science,state key laboratory of medical neurobiology,fudan university, shanghai,200032,china

＜正＞Cumulative evidences suggest that electroacupuncture（EA） can modulate immune function,but the mechanism needs further *** the present study,the contribution of EA on toll-like receptor 2 and 4（TLR2/TLR4） and proinflammatory cytokine expression after surgical trauma stress were *** mRNA level of both TLR2/4 and proinflammatory cytokine was measured by quantitative real-time *** and western blot assay were chosen for TLR2/ TLR4 protein expression and pro-inflammatory cytokine production *** results showed that surgical trauma stress increased TLR2 mRNA and TLR2/4 proteins in the spleen and augmented pro-inflammatory cytokines（***-1β） mRNA and protein expression in the spleen and *** effects could be deteriorated by adrenalectomy（ADX）.EA at "Zusanli" acupoint significantly inhibited surgical trauma induced TLR2 mRNA and TLR2/4 protein expression in spleen and pro-inflammatory cytokine expression in the spleen and ***,however,could not block the effect of *** results suggested that surgical trauma stress primes the innate immune system for enhanced TLR2 expression and pro-inflammatory cytokine *** inhibits TLR2/4 and pro-inflammatory cytokines to produce an anti-inflammatory effect in a surgical trauma stress model,without adrenal gland involvement.

关键词： electroacupuncture surgical trauma stress TLR pro-inflammatory cytokine adrenalectomy

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A practical model of bone inflammation induced pain by intra-tibial CFA injection in rats

A practical model of bone inflammation induced pain by intra...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Chang-Jiang YANG,Shan HU,Qian LI,Ping HAN,Gen-Cheng WU,Yan-Qing WANG,Qi-Liang MAOYING~* department of integrative medicine and neurobiology,shanghai medical college,Institute of Acupuncture research, institutes of brain Science,state key laboratory of medical neurobiology,fudan university,shanghai,china

＜正＞Background In prior studies,models of inflammatory pain have been produced through injecting complete Freund’s adjuvant（CFA） or capsaicin directly into either the deep somatic tissue or the plantar portion of animal hind *** contrast,bone cancer pain is simulated in animal by injecting tumor cells into the cavity of the femur or *** has been reported that the same stimulus to various tissues types might result in differing patterns of pain response due to differences in afferent *** The present study was designed to establish a rat model of inflammatory bone pain to better understand bone cancer *** Our rat model of inflammatory bone pain was produced through intra-tibial injection of *** in body weight,bone histology,mechanical allodynia and thermal hyperalgesia were *** effect of Celecoxib on inflammatory bone pain was also *** Significant inflammation was seen in the bone marrow two days after intra-tibial CFA injection, including nuclear condensation and fragmentation,massive neutrophilic granulocytes,and prominent fibrinous *** days after injection,marked fibrosis of the bone was detected by histological *** unilateral CFA injection,behavioral studies showed mechanical allodynia to von Frey hair stimulation,but no thermal hyperalgesia was *** showed significant anti-allodynic effects on the inflammatory bone pain induced by our *** CFA is an effective agent for inducing bone inflammation and subsequent pain-related behavior in rat *** described rat model of inflammatory bone pain induced by CFA provides a practical and valuable contrast for bone cancer pain research.

关键词： inflammatory bone pain CFA mechanical allodynia celecoxib rat

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