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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳志成(Chih-Cheng Chen) | |
| dc.contributor.author | Chia-Wen Wong | en |
| dc.contributor.author | 翁嘉文 | zh_TW |
| dc.date.accessioned | 2021-06-17T00:15:16Z | - |
| dc.date.available | 2017-07-20 | |
| dc.date.copyright | 2012-07-20 | |
| dc.date.issued | 2012 | |
| dc.date.submitted | 2012-07-04 | |
| dc.identifier.citation | References
1. Ahmad, I. U., Forman, J. D., Sarkar, F. H., Hillman, G. G., Heath, E., Vaishampayan, U., Cher, M. L., Andic, F., Rossi, P. J. and Kucuk, O. (2010) 'Soy isoflavones in conjunction with radiation therapy in patients with prostate cancer', Nutr Cancer 62(7): 996-1000. 2. Allred, C. D., Allred, K. F., Ju, Y. H., Virant, S. M. and Helferich, W. G. (2001) 'Soy Diets Containing Varying Amounts of Genistein Stimulate Growth of Estrogen-dependent (MCF-7) Tumors in a Dose-dependent Manner', Cancer Research 61(13): 5045-5050. 3. Basbaum, A. I., Bautista, D. M., Scherrer, G. and Julius, D. (2009) 'Cellular and molecular mechanisms of pain', Cell 139(2): 267-84. 4. Bevan, S. and Yeats, J. (1991) 'Protons activate a cation conductance in a sub-population of rat dorsal root ganglion neurones', The Journal of Physiology 433(1): 145-161. 5. Birdsong, W. T., Fierro, L., Williams, F. G., Spelta, V., Naves, L. A., Knowles, M., Marsh-Haffner, J., Adelman, J. P., Almers, W., Elde, R. P. et al. (2010) 'Sensing muscle ischemia: coincident detection of acid and ATP via interplay of two ion channels', Neuron 68(4): 739-49. 6. Chen, C. C., Zimmer, A., Sun, W. H., Hall, J. and Brownstein, M. J. (2002) 'A role for ASIC3 in the modulation of high-intensity pain stimuli', Proc Natl Acad Sci U S A 99(13): 8992-7. 7. Chen, W. K., Liu, I. Y., Chang, Y. T., Chen, Y. C., Yen, C. T., Shin, H. S. and Chen, C. C. (2010) 'Ca(v)3.2 T-type Ca2+ channel-dependent activation of ERK in paraventricular thalamus modulates acid-induced chronic muscle pain', J Neurosci 30(31): 10360-8. 8. Chen, Z., Janes, K., Chen, C., Doyle, T., Bryant, L., Tosh, D. K., Jacobson, K. A. and Salvemini, D. (2012) 'Controlling murine and rat chronic pain through A3 adenosine receptor activation', FASEB J 26(5): 1855-65. 9. Clauw, D. J. and Crofford, L. J. (2003) 'Chronic widespread pain and fibromyalgia: what we know, and what we need to know', Best Practice & Research Clinical Rheumatology 17(4): 685-701. 10. Deval, E., Gasull, X., Noel, J., Salinas, M., Baron, A., Diochot, S. and Lingueglia, E. (2010) 'Acid-Sensing Ion Channels (ASICs): Pharmacology and implication in pain', Pharmacology & Therapeutics 128(3): 549-558. 11. Duffy, C., Perez, K. and Partridge, A. (2007) 'Implications of phytoestrogen intake for breast cancer', CA Cancer J Clin 57(5): 260-77. 12. Gandhi, R., Ryals, J. M. and Wright, D. E. (2004) 'Neurotrophin-3 reverses chronic mechanical hyperalgesia induced by intramuscular acid injection', J Neurosci 24(42): 9405-13. 13. Giovannini Maria, G. (2006) The Role of the Extracellular Signal-regulated Kinase Pathway in Memory Encoding Reviews in the Neurosciences, vol. 17. 14. Hargreaves, K., Dubner, R., Brown, F., Flores, C. and Joris, J. (1988) 'A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia', Pain 32(1): 77-88. 15. Hayashi, Y. and Majewska, A. K. (2005) 'Dendritic Spine Geometry: Functional Implication and Regulation', Neuron 46(4): 529-532. 16. Hayashida, M., Fukuda, K. and Fukunaga, A. (2005) 'Clinical application of adenosine and ATP for pain control', J Anesth 19(3): 225-35. 17. Hill, R. (2000) 'NK1 (substance P) receptor antagonists – why are they not analgesic in humans?', Trends in Pharmacological Sciences 21(7): 244-246. 18. Hokfelt, T., Kellerth, J., Nilsson, G. and Pernow, B. (1975) 'Substance p: localization in the central nervous system and in some primary sensory neurons', Science 190(4217): 889-890. 19. Huang, N. K., Lin, J. H., Lin, J. T., Lin, C. I., Liu, E. M., Lin, C. J., Chen, W. P., Shen, Y. C., Chen, H. M., Chen, J. B. et al. (2011) 'A new drug design targeting the adenosinergic system for Huntington's disease', PLoS One 6(6): e20934. 20. Hucho, T. and Levine, J. D. (2007) 'Signaling Pathways in Sensitization: Toward a Nociceptor Cell Biology', Neuron 55(3): 365-376. 21. Igwe, O. J. (2003) 'c-Src kinase activation regulates preprotachykinin gene expression and substance P secretion in rat sensory ganglia', European Journal of Neuroscience 18(7): 1719-1730. 22. Ikeda, H., Heinke, B., Ruscheweyh, R. and Sandkuhler, J. (2003) 'Synaptic Plasticity in Spinal Lamina I Projection Neurons That Mediate Hyperalgesia', Science 299(5610): 1237-1240. 23. Issberner, U., Reeh, P. W. and Steen, K. H. (1996) 'Pain due to tissue acidosis: a mechanism for inflammatory and ischemic myalgia?', Neurosci Lett 208(3): 191-194. 24. Ji, R.-R., Gereau Iv, R. W., Malcangio, M. and Strichartz, G. R. (2009) 'MAP kinase and pain', Brain Research Reviews 60(1): 135-148. 25. Ji, R.-R., Kohno, T., Moore, K. A. and Woolf, C. J. (2003) 'Central sensitization and LTP: do pain and memory share similar mechanisms?', Trends in Neurosciences 26(12): 696-705. 26. Jones, N. G. (2004) 'Acid-Induced Pain and Its Modulation in Humans', Journal of Neuroscience 24(48): 10974-10979. 27. Jones, N. G., Slater, R., Cadiou, H., McNaughton, P. and McMahon, S. B. (2004) 'Acid-induced pain and its modulation in humans', J Neurosci 24(48): 10974-9. 28. Karczewski, J., Spencer, R. H., Garsky, V. M., Liang, A., Leitl, M. D., Cato, M. J., Cook, S. P., Kane, S. and Urban, M. O. (2010) 'Reversal of acid-induced and inflammatory pain by the selective ASIC3 inhibitor, APETx2', Br J Pharmacol 161(4): 950-60. 29. Katyal, J. and Gupta, Y. K. (2012) 'Dopamine release is involved in antinociceptive effect of theophylline', Int J Neurosci 122(1): 17-21. 30. Kim, S. K., Kato, G., Ishikawa, T. and Nabekura, J. (2011) 'Phase-specific plasticity of synaptic structures in the somatosensory cortex of living mice during neuropathic pain', Mol Pain 7: 87. 31. Krishtal, O. (2003) 'The ASICs: Signaling molecules? Modulators?', Trends in Neurosciences 26(9): 477-483. 32. Krishtal, O. A. and Pidoplichko, V. I. (1981) 'A receptor for protons in the membrane of sensory neurons may participate in nociception', Neuroscience 6(12): 2599-2601. 33. Ledent, C., Vaugeois, J.-M., Schiffmann, S. N., Pedrazzini, T., Yacoubi, M. E., Vanderhaeghen, J.-J., Costentin, J., Heath, J. K., Vassart, G. and Parmentier, M. (1997) 'Aggressiveness, hypoalgesia and high blood pressure in mice lacking the adenosine A2a receptor', Nature 388(6643): 674-678. 34. Li, L., Hao, J. X., Fredholm, B. B., Schulte, G., Wiesenfeld-Hallin, Z. and Xu, X. J. (2010) 'Peripheral adenosine A2A receptors are involved in carrageenan-induced mechanical hyperalgesia in mice', Neuroscience 170(3): 923-8. 35. Lin, C.-C. J., Chen, W.-N., Chen, C.-J., Lin, Y.-W., Zimmer, A. and Chen, C.-C. (2012) 'An antinociceptive role for substance P in acid-induced chronic muscle pain', Proceedings of the National Academy of Sciences 109(2): E76–E83. 36. Malhotra J, C. G., Gupta YK. (2000) 'Dopaminergic involvement in adenosine A1 receptor-mediated antinociception in the tail flick latency model in mice.', Methods Find Exp Clin Pharmacol 22(1): 37. 37. McBeth, J., Macfarlane, G. J. and Silman, A. J. (2002) 'Does chronic pain predict future psychological distress?', Pain 96(3): 239-245. 38. McClain, R. M., Wolz, E., Davidovich, A., Edwards, J. and Bausch, J. (2007) 'Reproductive safety studies with genistein in rats', Food Chem Toxicol 45(8): 1319-32. 39. Nielsen, A. N., Mathiesen, C. and Blackburn-Munro, G. (2004) 'Pharmacological characterisation of acid-induced muscle allodynia in rats', Eur J Pharmacol 487(1-3): 93-103. 40. Obata, K. and Noguchi, K. (2004) 'MAPK activation in nociceptive neurons and pain hypersensitivity', Life Sciences 74(21): 2643-2653. 41. Reeh, P. W. and Kress, M. (2001) 'Molecular physiology of proton transduction in nociceptors', Current Opinion in Pharmacology 1(1): 45-51. 42. Sakai, H., Lingueglia, E., Champigny, G., Mattei, M.-G. and Lazdunski, M. (1999) 'Cloning and functional expression of a novel degenerin-like Na+ channel gene in mammals', The Journal of Physiology 519(2): 323-333. 43. Sawynok, J. and Liu, X. J. (2003) 'Adenosine in the spinal cord and periphery: release and regulation of pain', Progress in Neurobiology 69(5): 313-340. 44. Shir, Y., Campbell, J. N., Raja, S. N. and Seltzer, Z. e. (2002) 'The Correlation Between Dietary Soy Phytoestrogens and Neuropathic Pain Behavior in Rats After Partial Denervation', Anesthesia & Analgesia 94(2): 421-426. 45. Skyba, D. A., King, E. W. and Sluka, K. A. (2002) 'Effects of NMDA and non-NMDA ionotropic glutamate receptor antagonists on the development and maintenance of hyperalgesia induced by repeated intramuscular injection of acidic saline', Pain 98(1–2): 69-78. 46. Sluka, K. A. (2009) 'Is it possible to develop an animal model of fibromyalgia?', Pain 146(1-2): 3-4. 47. Sluka, K. A., Kalra, A. and Moore, S. A. (2001) 'Unilateral intramuscular injections of acidic saline produce a bilateral, long-lasting hyperalgesia', Muscle & Nerve 24(1): 37-46. 48. Sluka, K. A., Price, M. P., Breese, N. M., Stucky, C. L., Wemmie, J. A. and Welsh, M. J. (2003) 'Chronic hyperalgesia induced by repeated acid injections in muscle is abolished by the loss of ASIC3, but not ASIC1', Pain 106(3): 229-239. 49. Sluka, K. A., Rohlwing, J. J., Bussey, R. A., Eikenberry, S. A. and Wilken, J. M. (2002) 'Chronic muscle pain induced by repeated acid Injection is reversed by spinally administered mu- and delta-, but not kappa-, opioid receptor agonists', J Pharmacol Exp Ther 302(3): 1146-50. 50. Staud, R., Nagel, S., Robinson, M. E. and Price, D. D. (2009) 'Enhanced central pain processing of fibromyalgia patients is maintained by muscle afferent input: a randomized, double-blind, placebo-controlled study', Pain 145(1-2): 96-104. 51. Steen, K., Reeh, P., Anton, F. and Handwerker, H. (1992) 'Protons selectively induce lasting excitation and sensitization to mechanical stimulation of nociceptors in rat skin, in vitro', The Journal of Neuroscience 12(1): 86-95. 52. Steen, K. H. and Reeh, P. W. (1993) 'Sustained graded pain and hyperalgesia from harmless experimental tissue acidosis in human skin', Neurosci Lett 154(1–2): 113-116. 53. Sutherland, S. P., Benson, C. J., Adelman, J. P. and McCleskey, E. W. (2001) 'Acid-sensing ion channel 3 matches the acid-gated current in cardiac ischemia-sensing neurons', Proc Natl Acad Sci U S A 98(2): 711-6. 54. Tacyildiz, N., Ozyoruk, D., Yavuz, G., Unal, E., Dincaslan, H., Dogu, F., Sahin, K. and Kucuk, O. (2010) 'Soy isoflavones ameliorate the adverse effects of chemotherapy in children', Nutr Cancer 62(7): 1001-5. 55. Terrillon, S. and Bouvier, M. (2004) 'Roles of G-protein-coupled receptor dimerization', EMBO Rep 5(1): 30-4. 56. Tracey, I. and Mantyh, P. W. (2007) 'The Cerebral Signature for Pain Perception and Its Modulation', Neuron 55(3): 377-391. 57. Ugawa, S. (2002) 'Amiloride-blockable acid-sensing ion channels are leading acid sensors expressed in human nociceptors', Journal of Clinical Investigation 110(8): 1185-1190. 58. Valsecchi, A. E., Franchi, S., Panerai, A. E., Rossi, A., Sacerdote, P. and Colleoni, M. (2011) 'The soy isoflavone genistein reverses oxidative and inflammatory state, neuropathic pain, neurotrophic and vasculature deficits in diabetes mouse model', Eur J Pharmacol 650(2-3): 694-702. 59. Valsecchi, A. E., Franchi, S., Panerai, A. E., Sacerdote, P., Trovato, A. E. and Colleoni, M. (2008) 'Genistein, a natural phytoestrogen from soy, relieves neuropathic pain following chronic constriction sciatic nerve injury in mice: anti-inflammatory and antioxidant activity', J Neurochem 107(1): 230-40. 60. Waldmann, R., Champigny, G., Bassilana, F., Heurteaux, C. and Lazdunski, M. (1997) 'A proton-gated cation channel involved in acid-sensing', Nature 386(6621): 173-177. 61. Waldmann, R. and Lazdunski, M. (1998) 'H+-gated cation channels: neuronal acid sensors in the NaC/DEG family of ion channels', Current Opinion in Neurobiology 8(3): 418-424. 62. Wemmie, J. A., Price, M. P. and Welsh, M. J. (2006) 'Acid-sensing ion channels: advances, questions and therapeutic opportunities', Trends Neurosci 29(10): 578-86. 63. Wemmie, J. A., Zha, X.-m. and Welsh, M. J. (2008) Acid-Sensing Ion Channels (ASICs) and pH in Synapse Physiology 64. Structural And Functional Organization Of The Synapse. in J. W. Hell and M. D. Ehlers (eds.): Springer US. 65. Yagi, J., Wenk, H. N., Naves, L. A. and McCleskey, E. W. (2006) 'Sustained Currents Through ASIC3 Ion Channels at the Modest pH Changes That Occur During Myocardial Ischemia', Circ Res 99(5): 501-509. 66. Zarate, E. S. R., Monica; White, Paul; PhD, MD; Duffy, Larry; Shearer, Vance; Griffin, James; Whitten, Charles (1999) 'Comparison of Adenosine and Remifentanil Infusions as Adjuvants to Desflurane Anesthesia.', Anesthesiology 90: 956-963. 67. Zhuang, Z.-Y., Gerner, P., Woolf, C. J. and Ji, R.-R. (2005) '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(1–2): 149-159. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/65915 | - |
| dc.description.abstract | 慢性肌肉疼痛在世界各地一直是個棘手的健康問題。近來有文章利用電生理技術觀察到，在肌肉釋放的P物質（SP）會抑制酸誘導第三型酸敏性離子通道(ASIC3)所產生的疼痛；而大豆異黃酮的成份之一，genistein，可扭轉SP抑制肌肉酸痛的機制。雖genistein具抗氧化活性和調節免疫的作用，我認為genistein可能透過抑制酪氨酸激酶(PTK)，在肌肉傳遞疼痛訊息的機制上扮演不利的角色。本研究發現，先給予genistein會使ASIC3野生型小鼠對酸誘導的痛覺敏感化更劇烈。但先給予genistein並不會使丘腦室旁核（PVA）的神經活性有顯著改變，對腹後丘腦核（VPM）和腹旁丘腦核（VPL）的樹突棘(dendritic spines)也無明顯影響。另外，長期給予genistein可延長酸誘導的痛覺敏感化。為尋找慢性肌肉疼痛的有效療法，我利用酸引起的肌肉疼痛模式，在小鼠體內測試一種自天麻萃取出的腺苷化合物，T1-11。在這項研究中，T1-11和酸性生理鹽水共同注射，可以逆轉genistein增強的疼痛過敏化。而同時注射酸、T1-11和第三型腺苷酸接受器(A3R)拮抗劑MRS1220，可抑制T1-11的作用；表示T1-11可能經由A3R訊息路徑發揮止痛作用。引人注目的是，在疼痛過敏化產生後，腹腔注射T1-11可在90分鐘內看見止痛效果，且藥效與劑量成正比。總結目前研究，先給予genistein會加強酸誘導的疼痛過敏化，而T1-11可經由A3R訊息路徑調節慢性肌肉疼痛達到有效的治療作用。 | zh_TW |
| dc.description.abstract | Chronic muscle pain is often accompanied with tissue acidosis and is an intractable health problem around the world. A recent article indicated that muscular substance P modulated an untraditional NK1 receptor signaling pathway to inhibit the acid-induced depolarization in muscle nociceptors; and genistein, one constituent of soy isoflavones, can reverse this inhibition on muscle nociceptor in vitro. Although genistein has antioxidant activity and beneficial effects on immune system modulation, I hypothesized genistein, as a tyrosine kinase inhibitor, may play a disadvantage role on ASIC3-mediated muscle pain. In the present study, I found that pretreating genistein followed by single acidic saline injection induced mechanical hyperalgesia in WT mice, but not in Asic3 KO mice. ERK activity was no significant changes in the paraventricular thalamic nucleus under genistein-pretreated condition, and dendritic spines in ventral posteromedial thalamic nucleus and ventral posterolateral thalamic nucleus had no changes. Moreover, mice with long-term genistein pretreatment prolonged the effect of acid-induced pain. In search for treatments for chronic muscle pain, I tested the therapeutic effect of a novel adenosine analogue T1-11, purified from Gastrodia elata, on the acid-induced muscle pain model. Co-injection of T1-11 and acidic saline after genistein prevented the chronic hyperalgesia. Coinjecting T1-11 and MRS1220, a selective A3R antagonist, reversed the antinociceptive effect of T1-11, indicating an A3R-dependent signaling involved. Strikingly, after the mechanical hyperalgesia had been developed, intraperitoneal injections of T1-11 can rescue the pain effect dosage-dependently within 90 minutes. Together, the present study indicates that pretreating genistein promotes acid-induced chronic muscle pain, whereas T1-11-A3R signaling inhibits the pain. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T00:15:16Z (GMT). No. of bitstreams: 1 ntu-101-R99B41025-1.pdf: 2766852 bytes, checksum: 073e51e20f48577a5c0d22f8c5d37bee (MD5) Previous issue date: 2012 | en |
| dc.description.tableofcontents | Table of Contents
口試委員會審定書………………………………………………………………………i Acknowledgement…..…………………………………………………………………...ii 中文摘要………………………………………………………………………………..iii Abstract………………………………………………………………………………….iv Table of Contents………………………………………………………………………..vi List of Figures……………………………………………………………………….....xii Chapter 1: Introduction…………………………………………………………...1 1.1 Chronic widespread muscle pain..……………………………………………..1 1.2 Acid-induced chronic mechanical hyperalgesia………………………………..2 1.3 Role of ASIC3 in acid-sensing…………………………………………………3 1.4 The antinociceptive role of substance P in muscle…………………………….5 1.5 Role of genistein in pain……………………………………………………….6 1.6 Role of adenosine in pain………………………………………………………8 1.7 Objectives………………………………………………………………………9 Chapter 2: Material & Methods……………..………………………………...10 2.1 Animals...……………………………………………………………………...10 2.2 Acute procedure for mechanical and thermal testing…………………………10 2.2.1 Drug injections………………………………………………………...10 2.2.2 Von Frey filament testing………………………………………………11 2.2.3 Radiant heat test………………………………………………………..12 2.3 Long-term procedure for behavior testing…………………………………….12 2.3.1 Drug injections………………………………………………………...12 2.3.2 Von Frey filament testing………………………………………………13 2.3.3 General behaviors in novel cage……………………………………….13 2.3.4 Forced-swimming test…………………………………………………14 2.4 Procedure for mechanism finding……………………………………………..14 2.4.1 Drug injections………………………………………………………...14 2.4.2 Von Frey filament testing………………………………………………15 2.4.3 Forced-swimming test………………………………………………....16 2.5 Procedure for therapeutic timing issue………..………………………………16 2.5.1 Drug injection………………………………………………………….16 2.5.2 Von Frey filament testing………………………………………………17 2.6 Procedure for therapy finding…………………………………………………17 2.6.1 Drug injection………………………………………………………….17 2.6.2 Von Frey filament testing………………………………………………19 2.7 Brain Immunochemistry………………………………………………………20 2.7.1 Sample preparation…………………………………………………….20 2.7.2 Immunostaining………………………………………………………..21 2.8 Brain Golgi staining…………………………………………………………...21 2.9 Data analysis……………….………………………………………………….22 Chapter 3: Results…………………………………………………………………23 3.1 Acute effect of genistein on acid-induced chronic muscle pain………………23 3.1.1 Genistein pretreatment followed by single acid injection induced long-term mechanical hyperalgesia in Asic3+/+ female mice bilaterally…...23 3.1.2 Genistein pretreatment followed by single acid injection has no effect on thermal nociception in Asic3+/+ and Asic3-/- female mice…………….……24 3.1.3 ERK activity had no significant changes in paraventricular thalamic nucleus (PVA) under genistein pretreated condition………………….……25 3.1.4 Dendritic spines had no significant changes in paraventricular thalamic nucleus (PVA), ventral posteriomedial thalamic nucleus (VPM) and ventral posteriolateral thalamic nucleus (VPL) under genistein pretreated condition…………………………………………………………………....27 3.2 Effect of long-term genistein treatment on acid-induced chronic muscle pain.28 3.2.1 Long-term Genistein treatment prolongs acid-induced mechanical hyperalgesia in Asic3+/+ female mice bilaterally…………………………...28 3.2.2 Long-term Genistein treatment has no significant effect to general and depression-like behaviors……………………………………………...29 3.3 A novel adenosine analogue T1-11 for chronic muscle pain treatment…….....30 3.3.1 The antinociceptive effect of T1-11 for chronic muscle pain………….30 3.4 The preliminary finding of T1-11 receptors that inhibit acid-induced chronic muscle pain………………………………………………………………………31 3.4.1 Adenosine 2a receptor (A2AR) agonist, but not adenosine 3 receptor (A3R) agonist partially prevents the acid-induced hyperalgesia developed in vivo…………………………………………………………………………31 3.4.2 A3R is involved in T1-11 mediated antinociceptive signaling in chronic muscle pain model………………………………………………………….32 3.5 The therapeutic effect of T1-11 on acid-induced muscle pain………………...33 3.5.1 Time issue of the T1-11 treatment efficiency………………………….33 3.5.2 Intraperitoneal T1-11 treatment show analgesic effect dose-dependently……………………………………………………...……34 3.5.3 Mice with high dose of intraperitoneal T1-11 injections show sedative Effect……..…………………………………………………………………34 3.5.4 High dose of A2AR agonist and A3R agonist intraperitoneal treatments both showed sedative and analgesic effect on mice with hyperalgesia…….35 3.5.5 Intraperitoneal injection of non-selective adenosine receptor antagonist, theophylline, or coinjection of T1-11 and theophylline had no effect on muscles that have developed mechanical hyperalgesia……………………36 3.5.6 Repeated intramuscular T1-11 injections have transient and tolerant analgesic effect on mechanical hyperalgesia……………………………….37 Chapter 4: Discussion…………………………………………………………….39 4.1 Unilateral genistein pretreatment followed by single acid injection promote bilateral mechanical hyperalgesia, but not thermal effect on acid-induced chronic muscle pain model.………………………………………………….…………...39 4.2 Brain changes after induction of hyperalgesia………………………………..41 4.2.1 Neuronal activity after induction of hyperalgesia in PVA………….….41 4.2.2 Neuronal plasticity after induction of hyperalgesia in PVA, VPM and VPL…………………………………………………………………………43 4.3 Effect of long-term genistein treatment on acid-induced chronic muscle pain.45 4.3.1 Genistein pretreatment prolongs repeated acid-induced hyperalgesia...45 4.3.2 Long-term genistein treatment has no effect on general and depression-like behaviors……………………………………………….….45 4.4 A3R is involved in the T1-11-mediated antinociceptive signaling in chronic muscle pain model……………………………………………………….………46 4.5 Therapy and sedative effect of T1-11 in chronic muscle pain model…………47 Chapter 5: Conclusion………………………………………………………..…..50 References………………………………………………………………………..…..51 List of Figures Figure 1. The schematic of pain signaling transduction in muscle nociceptors.……….62 Figure 2. Pretreating genistein followed by single acidic saline injection induced a long-term bilaterally mechanical hyperalgesia in Asic3+/+ female mice……..…….63 Figure 3. Pretreating genistein followed by single acidic saline injection had no effect on thermal stimulation in Asic3+/+ female mice………………………………..…..64 Figure 4. ERK activity had no significant changes in paraventricular thalamic nucleus (PVA) under genistein pretreated and/or acid injection conditions………………...65 Figure 5. A variety of neural cell types in the PVA region.……………………….……67 Figure 6. The major groups of PVA neurons had no significant change in dendritic spines under genistein pretreating and/or acid injection conditions………….…….68 Figure 7. The octopus-like neurons on ventral posterior medial thalamic nucleus (VPM) and ventral posterior lateral thalamic nucleus (VPL) had no significant changes in dendritic spines under genistein pretreating and/or acid injection conditions……...69 Figure 8. Mice with long-term genistein treatment showed prolonged hyperalgesia effect in the repeated acid-induced chronic muscle pain model……………………70 Figure 9. General behaviors had no significant changes after long-term genistein treatment……………………………………………………………………..……..71 Figure 10. Depression-like behaviors had no significant changes after long-term genistein treatment…………………………………………………………………72 Figure 11. T1-11 prevents the chronic hyperalgesia effect of genistein pretreatment on acid-induced muscle pain……………………………………………………..……73 Figure 12. The effects of adenosine receptor agonists on genistein-pretreating acid-induced muscle pain………………………………………………………..…74 Figure 13. With T1-11 or A2aR and acid coinjection, there was no difference in depression-like behaviors between groups under genistein pretreated condition.…75 Figure 14. An Adenosine 3 receptor (A3R)-dependent signaling is involved in the antinociceptive role of T1-11…………………………………………………….…76 Figure 15. Time-dependent therapeutic effect of single intramuscular T1-11 dosage…77 Figure 16. Intraperitoneal injections of T1-11 show dose-dependent analgesic effect on mice that have developed mechanical hyperalgesia…………………..……………78 Figure 17. Mice with high doses of intraperitoneal T1-11 injections show sedative effect……………………………………………………………………………………79 Figure 18. Intraperitoneal A2aR agonist or A3R agonist injections show transient analgesic effect on mice that have developed mechanical hyperalgesia……...……80 Figure 19. Intraperitoneal injection of non-selective adenosine receptor antagonist, theophylline, or coinjection of T1-11 and theophylline had no effect on mice that have developed mechanical hyperalgesia……………………………………….….81 Figure 20. Repeated intramuscular T1-11 injections show transient analgesic effect and tolerant sedative effect on mice, that have developed mechanical hyperalgesia in the acid-induced chronic muscle pain model……………………………………..……82 Figure 21. The schematic of pain signaling transduction in muscle nociceptor………..83 Figure S1. Data comparison between two image-countingmethods………………...…84 Figure S2. General behaviors observation after T1-11 injection……………………….85 | |
| dc.language.iso | zh-TW | |
| dc.subject | 肌肉 | zh_TW |
| dc.subject | T1-11 | zh_TW |
| dc.subject | 酸 | zh_TW |
| dc.subject | 大豆異黃酮 | zh_TW |
| dc.subject | 疼痛過敏化 | zh_TW |
| dc.subject | T1-11 | en |
| dc.subject | genistein | en |
| dc.subject | hyperalgesia | en |
| dc.subject | acid | en |
| dc.subject | muscle | en |
| dc.title | 大豆異黃酮和天麻萃取物T1-11對酸引起的慢性肌肉疼痛所造成的影響 | zh_TW |
| dc.title | Effect of Soy Isoflavones Genistein and Gastrodia elata Extraction T1-11 on Acid-induced Chronic Muscle Pain | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 100-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 閔明源(Ming-Yuan Min),陳建璋(Chien-Chang Chen),孫維欣(Wei-Hsin Sun) | |
| dc.subject.keyword | 肌肉,酸,疼痛過敏化,大豆異黃酮,T1-11, | zh_TW |
| dc.subject.keyword | muscle,acid,hyperalgesia,genistein,T1-11, | en |
| dc.relation.page | 85 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2012-07-04 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 動物學研究所 | zh_TW |
| 顯示於系所單位： | 動物學研究所 | |
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