請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/32091
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳志成(Chih-Cheng Chen) | |
dc.contributor.author | Chien-Hung Liu | en |
dc.contributor.author | 劉建宏 | zh_TW |
dc.date.accessioned | 2021-06-13T03:31:19Z | - |
dc.date.available | 2006-07-31 | |
dc.date.copyright | 2006-07-31 | |
dc.date.issued | 2006 | |
dc.date.submitted | 2006-07-27 | |
dc.identifier.citation | Alvarez de la Rosa, D., Zhang, P., Shao, D., White, F. & Canessa, C.M. Functional implications of the localization and activity of acid-sensitive channels in rat peripheral nervous system. Proc. Natl. Acad. Sci. USA 99(4), 2326-2331 (2002).
Alvarez de la Rosa, D., Krueger, S.R., Kolar, A., Shao, D., Fitzsimonds, R.M. & Canessa, C.M. Distribution, subcellular localization and ontogeny of ASIC1 in the mammalian central nervous system. J. Physiol. 546(1), 77-87 (2003). Armstrong, C.M.& Hille, B. Voltage-gated ion channels and electrical excitability. Neuron 20, 371-380 (1998). Askwith, C.C., Benson C.J., Welsh, M.J & Snyder, P.M. DEG/ENaC ion channels involved in sensory transduction are modulated by cold temperature. Proc. Natl. Acad. Sci. USA 98(11), 6459-6463. (2001). Benson, C.J., Eckert, S.P. & McCleskey E.W. Acid-evoked currents in cardiac sensory neurons : a possible mediator of myocardial ischemic sensation. Circ. Res. 84, 921-928 (1999). Bianchi, L. & Driscoll, M. Protons at the gate: DEG./ENaC ion channels help us feel and remember. Neuron 34, 337-340 (2002). Chen, C.C., Zimmer, A., Sun, W.H., Hall, J., Brownstein, M.J. and Zimmer A. A role for ASIC3 in the modulation of high-intensity pain stimuli. Proc. Natl. Acad. Sci. USA 99(13), 8992-8997 (2002). Chuang, H.H., Prescott, E.D., Kong, H., Shields, S., Jordt, S.E., Basbaum, A.I., Chao, M.V. & Julius, D. Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition. Nature 411, 957-962 (2001). Costigan, M. & Woolf, C.J. Pain: molecular mechanisms. J. Pain. Suppl. 1, 35-44 (2000). Costigan, M. and Woolf, C.J. No DREAM, No pain. Closing the spinal gate. Cell 108(3), 297-300 (2002). Edwards, L., Nachmi, R., Jones, O., Backx,P., Ackerley, C., Becker, L. & Fehlings, M.G. Upregulation of Kv 1.4 protein and gene expression after chronic spinal cord injury. J. Compa. Neurol. 443, 154-167 (2002). Gold, M.S., Levine, J.D. & Correa, A.M. Modulation of TTX-R INa by PKC and PKA and their role in PGE2-induced sensitization of rat sensory neurons in vitro. J. Neurosci. 18(24), 10345-10355. (1998). Hamamoto, D.T., Ortiz-Gonzalez, X.R., Honda, J.M. & Kajander, K.C. Intraplantar injection of hyaluronic acid at low pH into the rat hindpaw produces tissue acidosis and enhances withdrawal responses to mechanical stimuli. Pain 74(2-3), 225-34 (1998). Hunskaar, S. & Hole, K. The formalin test in mice: dissociation between inflammatory and non-inflammatory pain. Pain 30, 103-114 (1987). Hunt, S.P. & Mantyh, P.W. The molecular dymamics of pain control. Nature Review Neurosci. 2, 83-91 (2001). Ikeda, H., Heinke, B., Ruscheweyh, R. & Sandkühler, J. Synaptic plasticity in spinal lamina I projection neurons that mediate hyperalgesia. Science 299, 1237-1240 (2003). Immke, D.C. & McCleskey, E.W. ASIC3: a lactic acid sensor for cardiac pain. ScientificWorldJournal. 1, 510-512 (2001). Immke, D.C. & McCleskey E.W. Lactate enhances the acid-sensing Na+ channel on ischemia-sensing neurons. Nat Neurosci. 4(9), 869-870 (2001). Issberner, U., Reeh, P.W. & Steen, K.H. Pain due to tissue acidosis: a mechanism for inflammatory and ischemic myalgia? Neurosci. Lett. 208, 191-194 (1996). Ji, R.R. & Woolf, C.J. Neuronal plasticity and signal transduction in nociceptive neurons: implications for the initiation and maintenance of pathological pain. Neurobiol Dis. 8(1), 1-10 (2001). Ji, R.R., Befort, K., Brenner, G.J. & Woolf, C.J. ERK MAP kinase activation in superficial spinal cord neurons induces prodynorphin and NK-1 upregulation and contributes to persistent inflammatory pain hypersensitivity. J. Neurosci. 22(2), 478-485 (2002). Ji, R.R., Kohno, T., Moore, K.A. & Woolf, C.J. Central sensitization and LTP: do pain and memory share similar mechanisms? Trends Neurosci. 26(12), 696-705 (2003). Jin, S.X., Zhuang, Z.Y., Woolf, C.J. & Ji, R.R. p38 Mitogen-Activated Protein Kinase is activated after a spinal nerve ligation in spinal cord microglia and dorsal root ganglion neurons and contributes to the generation of neuropathic pain. J. Neurosci. 23(10), 4017-4022 (2003). Jones, E.G. Cortical and subcortical contributions to activity-dependent plasticity in primate somatosensory cortex. Annu. Rev. Neurosci. 23, 1-37 (2000). Jones, N.G., Slater, R., Cadiou, H., McNaughton, P. & McMahon, S.B. J neurosci. 48,10974-10979 (2004). Juluus, D. and Basbaum, A.I. Molecular mechanisms of nociception. Nature 413, 203-201 (2001). Kawasaki, Y., Kohno, T., Zhuang, Z.Y., Brenner, H.W., Meer, C.V.D., Befort, K., Woolf, C.J. & Ji, R.R. Ionotropic and metabotropic receptors, protein kinase A, protein kinase C, and Src contribute to C-fiber-induced ERK activation and cAMP response element-binding protein phosphorylation in dorsal horn neurons, leading to central sensitization. J. Neurosci. 24(38), 8310-8321 (2004). King, T., Gardell, L.R., Wand, R., Vardanyan, A., Ossipov, M.H. Jr.,T.P.M., Vanderah, T.W., Hunt, S.P., Hruby, V.J., Lai, J. & Porreca, F. Role of NK-1 neurotransmission in opioid-induced hyperalgesia. Pain 116, 276-288 (2005). Krishtal, O.A. & Pidoplichko, V.I. A 'receptor' for protons in small neurons of trigeminal ganglia: possible role in nociception. Neurosci. Lett. 24(3), 243-246 (1981). Krishtal, Oleg. The ASCIs: Signaling molecules? Modulators? Trands in Neurosci. 26, 477-483 (2003). Luján, R., de Cabo de la Vega, C., Dominguez del Toro, E., Ballesta, J.J., Criado, M. & Juiz, J.M. Immunohistochemical localization of the voltage-gated potassium channel subunit Kv1.4 in the central nerevous system of the adult rat. J. Chem. Neuroanat. 26(3), 209-224 (2003). Manthy, P.W., Rogers, S.D. Honore, P. Allen, B.J., Ghilardi, J.R., Li, Jun.,Daughters, R.S., Lappi, D.A., Wiley, R.G. &Simone D.A. Inhibition of hyperalgesia by ablation of laminaI spinal neurons expressing the substance P receptor. Science 278, 275-279 (1997). Mense, S. Nociception from skeletal muscle in relation to clinical muscle pain. Pain 54, 241-289 (1993). Molliver, D.C., Immke, D.C., Fierro, L., Pare, M., Rice, F.L. & McCleskey, E.W. ASIC3, an acid-sensing ion channel, is expressed in metaboreceptive sensory neurons. Mol. Pain 1, 35-48 (2005). Porreca, F., Ossipov, M.H. & Gebhart, G.F. Chronic pain and medullary descending facilitation. Trends Neurosci. 25(6), 319-25 (2002). Price, M.P., Snyder, P.M. & Welsh, M.J. Cloning and expression of a novel human brain Na+ channel. J. Biol. Chem. 271(14), 7879-7882 (1996). Price, M.P., Lewin, G.R., Mcllwrath, S.L., Cheng, C., Xie, J.H., Heppenstall, P.A., Stuckky, C.L., Mannsfeldt, A.G. Brennan, T.J. Drummond H.A., Qiao, J. Benson, C.J., Tarr, D.E., Hrstka, R.F., Yang, B., Williamson, R.A. & Welsh, M.J. The mammalian sodium channel BNC1 is required for normal touch sensation. Nature 407, 1007-1010 (2000). Price, M.P., McIlwrath, S.L., Xie, J., Cheng, C., Qiao, J., Tarr, D.E., Sluka, K.A., Brennan, T.J., Lewin, G.R. & Welsh, M.J. The DRASIC cation channel contributes to the detection of cutaneous touch and acid stimuli in mice. Neuron. 23(6), 1071-1083 (2001). Reeh, P.W. & Steen, K.H. Tissue acidosis in nociception and pain. Prog Brain Res. 113, 143-151 (1996). Scholz, J. & Woolf, C.J. Can we conquer pain? Nature Neurosci. suppl. 5, 1062-1067 (2002). Sluka, K.A., King, E.W. & Sluka, K.A. Effects of NMDA and non-NMDA ionntropic gultamate receptor antagonists on the development and maintenance of hyperalgesia induced by repeated intramuscular injection of acidic saline. Pain 98, 69-78 (2002). Sluka, K.A., Kalara, A. & Moore, S.A. Unilateral intramuscular injections of acidic saline produce a bilateral, long-lasting hyperalgesia. Muscle Nerve 24, 37-46 (2001). Sluka, K.A., Rohlwing, J.J., Bussey, R.A., Eikenberry, S.A. & Wilken J.W. Chronic muscle pain induced by repeated acid injection is reversed by spinally administered μ- and δ-, but not κ-, opioid receptor agonists. J Pharmacol Exp Ther. 302(3), 1146-1150 (2002). Sluka, K.A., Price, M.P., Breese, N.M., Stucky, C.L., Wemmie, J.A. & Welsh, M.J. chronic hyperalgesia induced by repeated acid injections in muscle is abolished by the loss of ASIC3, but not ASIC1. Pain 106, 229-239 (2003). Steen, K.H. & Reeh, P.W. Sustained graded pain and hyperalgesia from harmless experimental tissue. Neurosci. Lett. 154, 113-116(1993). Sutherland, S.P., Benson, C.J., Adelman, J.P. and McCleskey E.W. Acid-sensing ion channel 3 matches the acid-gated current in cardiac ischemia-sensing neurons. Proc. Natl. Acda. Sci. USA 98(2), 711-716 (2001). Talley, E.M., Cribbs,L.L., Lee, J.H., Daud, A., Perez-Reyes, E. & Bayliss, D.A. Differential distribution of three members of a gene family encoding low voltage-activated (T-type) calcium channels. J. Neurosci. 19(6), 1895-1911 (1999). Tegeder, I., Zimmermann1, J., Meller, S.T. & Geisslinger, G. Release of algesic substances in human experimental muscle pain. Inflamm. Res. 51, 392-402 (2002). Tjølsen, A., Berge, O.G., Hunskaar S., Rosland, J.H. & Hole K. The formalin test: an evaluation of the method. Pain 51, 5-17 (1992). Ugawa, S., Ueda, T., Ishida, Y., Nishigaki, M., Shibata, Y. & Shimada, S. Amiloride-blockable acid-sensing ion channels are leading acid sensors expressed in human nociceptors. J Clin. Invest. 110, 1185-1190 (2002). Voilley, N., de Weille, J., Mamet, J. & Lazdunski, M. Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors. J. Neurosci. 21(20), 8026-33 (2001). Waldmann, R., & Lazdunski, M. H+-gated cation channels: neuronal acid sensors in the NaC/DEG family of ion channels. Curr Opin Neurobiol. 8(3), 418-424 (1998). Waxman, S.G. The molecular pathophysiology of pain: abnormal expression of sodium channel genes and its contributions to hyperexcitability of primary sensory neurons. Pain Suppl. 6, S133-S140 (1999). Wemmie, J.A., Chen, J., Askwith, C.C., Hruska-Hageman, A.M., Price, M.P., Nolan, B.C., Yoder, P.G., Lamani, E., Hoshi, T., Freeman, J.H. Jr. & Welsh, M.J. The acid-activated ion channel ASIC contributes to synaptic plasticity, learning, and memory. Neuron 34(3), 463-477 (2002). Wood, J.N., Boorman, J.P., Okuse, K. & Baker, M.D. Voltage-gated sodium channels and pain pathways. J Neurobiol. 61(1), 55-71 (2004). Woolf, C.J & King, A.E. Subthreshold components of the cutaneous mechanoreceptive fields of dorsal horn neurons in the rat lumbar spinal cord. J. Neurophysiol. 62, 907-916 (1989). Woolf, C.J. & Costigan, M. Transcriptional and posttranslational plasticity and the generation of inflammatory pain. Proc. Natl. Acad. Sci. USA 96, 7723-7730 (1999). Woolf, C.J. & Mannoion, R.J. Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet 353, 1959-194 (1999). Woolf, C.J. & Salter, M.W. Neuronal plasticity: increasing the gain in pain. Science 288, 1765-1768 (2000). Yelin, E. & Callahan, L.F. The economic costs and social and psychological impact of musculoskeletal condictions. Arthritis. Rheumatism 38, 1351-1362 (1995). Yunker, A.M. & McEnery, M.W. Low-voltage-activated (“T-type”) calcium channels in review. J Bioenerg. Biomembr. 35(6), 533-575 (2003). Zhuang, Z.Y., Gerner, P., Woolf, C.J. & Ji, R.R. ERK is sequentially activated in neurons, microglia, and astrocytes by spinal nerve ligation and contributes to mechanical allodynia in this neuropathic pain model. Pain 114, 149-159 (2005). | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/32091 | - |
dc.description.abstract | 酸是眾多可活化痛覺受器的刺激物之ㄧ,組織酸化現象常常伴隨著疼痛的發生,因此生理上主要負責偵測組織中酸濃度為神經細胞上的酸敏感離子孔道(Acid-sensing ion channels, ASICs),其中又以ASIC3亞型對酸最為敏感。最近研究報導指出重複地在單側腓腸肌內注射酸性生理食鹽水可引起兩側腳掌長期痛覺過敏的現象。又因為長期、慢性的痛覺通常與中樞敏感化有關,此時脊髓內部的基因表現量改變,以類似建立LTP的機制造成中樞神經細胞的活性增加、動作電位閾值降低。因此本篇論文的目的在尋找一系列與中樞敏感化及動作電位相關的基因當中,何者基因表現量改變,並與長期痛覺過敏有關聯。由定量PCR的結果指出在腰椎部位的脊髓內,膜電位依賴性鈣離子孔道Cav3.2在第一次注射酸後五天,基因表現量增加了22倍,並持續增加到第二次注射酸後七天時,基因表現量增為24倍;此外膜電位依賴性鉀離子孔道Kv1.4在第二次注射酸後24小時,至第二次注射酸後七天,期間基因表現量一直維持21倍的增加。然而一般源自皮膚刺激而引起的中樞敏感化相關基因,包括NK1、Pdyn及一些麩胺酸(glutamate)受體等等,在本論文中則皆未觀察到表現量有任何變化。以上結果指出T型鈣離子孔道(T-type Calcium channels) Cav3.2的基因表現量與A型鉀離子孔道(A-type Potassium channels) Kv1.4的基因表現量增加的時間點與行為實驗中的長期痛覺過敏時間點相吻合,因此認為這兩個離子孔道在肌肉內施予酸刺激造成的長期痛覺過敏的機制中扮演很重要的角色,並且這種機制是不同於以往源自皮膚刺激的實驗模式。
另外在皮下組織進行福馬林測試(formalin test),並利用乳酸與低溫兩種變因來促進在皮膚層面ASIC3的作用,結果發現乳酸存在時並不影響福馬林引起的發炎痛覺;低溫條件下也只能延遲痛覺的反應時間而已。這個結果指出皮膚層面的ASIC3被活化後,對於調控發炎反應痛覺的作用不大。 | zh_TW |
dc.description.abstract | Acid is one of the chemical mediators that cause pain. Sensory neurons detect the pH drop of surrounding tissue when tissue acidosis occurs. The main ion channels responsible for detecting protons are acid-sensing ion channels called ASICs. Within this ASIC family, ASIC3 is the most sensitive to protons. A recent article showed that repeated acid-injection into muscle can induce bilateral long-lasting hyperalgesia. This experimental model is helpful for us to investigate chronic muscle-originated pain. Chronic or long-term nociception is always related to central sensitization, which is involved in a transcription-dependent mechanism for developing long-term potential effect. Therefore I used QPCR technique to exam gene expression level before and after acid-injection to see if any genes involved in central sensitization. Based on my QPCR data, a T-type Calcium channel, Cav3.2 was up-regulated 22 folds in 5th day after 1st acid-injection and 24 folds in 7th day after 2nd acid-injection and an A-type potassium channel, Kv1.4 was up-regulated 21 fold from 24hrs after 2nd acid-injection to 7th day after 2nd acid-injection. Comparing with behavioral tests, up-regulation of both genes is associated with the development of chronic hyperalgesia. It suggests that increasing expression levels of Cav3.2 and Kv1.4 in lumbar spinal cord may contribute hyperalgesia formation. However, the expression levels of NK1、Pdyn and some gultamate receptors, which are up-regulated after central sensitization induced by cutaneous stimulation, were constant in my experiment model. My data suggest that the mechanism of muscle-originated chronic hyperalgesia is different from skin-originated chronic hyperalgesia..
Another part of the thesis studied the effect of lactate and cold temperature in cutaneous formalin test. The result showed that both lactate and cold temperature did not affect the cutaneous inflammatory nociception but the formalin-induced late phase nociception was delayed. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T03:31:19Z (GMT). No. of bitstreams: 1 ntu-95-R93b41023-1.pdf: 1798027 bytes, checksum: 867b8113593b6845d4119db1bc7cd0ea (MD5) Previous issue date: 2006 | en |
dc.description.tableofcontents | 中文摘要……………………………...……………………………………………III
英文摘要…………………………………………...………………………………IV 第一章、 總序.........................................................................................................1 1.1 痛覺……………………………………………….………………..………2 1.2 痛覺的訊息傳導途徑……………………………………………...………3 1.3 酸與痛…………………………………………………………...…………4 1.4 酸敏感離子孔道(ASICs)家族…………………………...…………..……4 第二章、 肌肉內注射酸導致長期痛覺過敏.................................................7 2.1 序言 2.1.1 酸與肌肉的傷害受器(nociceptors)………....……………....……..8 2.1.2 酸誘導痛覺過敏……………………………………………………9 2.1.3 周邊神經系統敏感化(peripheral sensitization)…..………………10 2.1.4 中樞神經系統敏感化(central sensitization)………...………...….11 2.1.5 實驗動機與目的…………………………………..………………12 2.2 實驗材料與方法 2.2.1 實驗動物………………………………………..…………………13 2.2.2 肌肉內注射酸性生理食鹽水……………………..………………13 2.2.3 動物行為測試 (Von Frey Filament)………………….…………..13 2.2.4 萃取組織RNA………………………………………….…………14 2.2.5 合成互補去氧核醣核酸(cDNA)……………………………...….15 2.2.6 引子設計(Primer design)………………………………………….15 2.2.7 聚合酶連鎖反應(PCR) 2.2.7.1 反轉錄酶之聚合酶連鎖反應(RT-PCR)…………...……..15 2.2.7.2 同步定量PCR系統(Real-Time Quantitative PCR, QPCR)……………………………………………..…….16 2.2.8 組織切片……………………………………………………..……17 2.2.9 免疫染色…………………………………………………..………17 2.3 實驗結果……………………………………………………..……………19 2.4 實驗討論…………………………………………………..………………23 第三章、 乳酸在福馬林誘導痛覺模式中的影響......................................35 3.1 序言 3.1.1 福馬林試驗……………………………..…………………………36 3.1.2 影響酸離子孔道特性之刺激物………..…………………………37 3.1.2.1 乳酸………………………………..………………………37 3.1.2.2 溫度……………………………..…………………………37 3.1.3 實驗動機與目的……………………………..……………………38 3.2 實驗材料與方法 3.2.1 福馬林試驗……………………………………..…………………39 3.2.1.1 實驗動物 3.2.1.2 藥物配製與注射 3.2.1.3 動物行為觀察 3.2.2 資料分析…………………………………..………………………40 3.3 實驗結果…………………………………………..………………………41 3.4 實驗討論………………………………………………..…………………44 第四章、 總結與討論……………………………….…………………………51 第五章、 參考文獻….............……………………….…………………………52 附表一、引子序列.................................................................................................59 | |
dc.language.iso | zh-TW | |
dc.title | 酸刺激肌肉所誘導長期痛覺過敏時其脊髓內基因表現量之差異 | zh_TW |
dc.title | The difference of gene expression in spinal cord during intramuscular acid-induced chronic hyperalgesia | en |
dc.type | Thesis | |
dc.date.schoolyear | 94-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 閔明源,黃翊恭,孫維欣 | |
dc.subject.keyword | 肌肉內,酸注射,長期痛覺過敏, | zh_TW |
dc.subject.keyword | muscle,acid,chronic hyperalgesia, | en |
dc.relation.page | 60 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2006-07-28 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 動物學研究研究所 | zh_TW |
顯示於系所單位: | 動物學研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-95-1.pdf 目前未授權公開取用 | 1.76 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。