請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/20725
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳志成 | |
dc.contributor.author | Chu-Ting Chang | en |
dc.contributor.author | 張筑婷 | zh_TW |
dc.date.accessioned | 2021-06-08T03:00:30Z | - |
dc.date.copyright | 2017-08-01 | |
dc.date.issued | 2017 | |
dc.date.submitted | 2017-07-26 | |
dc.identifier.citation | 1. US, V.E. and J.H. Gaddum, An unidentified depressor substance in certain tissue extracts. J Physiol, 1931. 72(1): p. 74-87.
2. Chang, M.M. and S.E. Leeman, Isolation of a sialogogic peptide from bovine hypothalamic tissue and its characterization as substance P. J Biol Chem, 1970. 245(18): p. 4784-90. 3. Stewart, J.M., et al., Substance P and analgesia. Nature, 1976. 262(5571): p. 784-5. 4. Krause, J.E., et al., Three rat preprotachykinin mRNAs encode the neuropeptides substance P and neurokinin A. Proc Natl Acad Sci U S A, 1987. 84(3): p. 881-5. 5. Macdonald, S.G., J.J. Dumas, and N.D. Boyd, Chemical cross-linking of the substance P (NK-1) receptor to the alpha subunits of the G proteins Gq and G11. Biochemistry, 1996. 35(9): p. 2909-16. 6. Meza, U., et al., Neurokinin 1 receptors trigger overlapping stimulation and inhibition of CaV2.3 (R-type) calcium channels. Mol Pharmacol, 2007. 71(1): p. 284-93. 7. Meshki, J., et al., Neurokinin 1 receptor mediates membrane blebbing in HEK293 cells through a Rho/Rho-associated coiled-coil kinase-dependent mechanism. J Biol Chem, 2009. 284(14): p. 9280-9. 8. Roush, E.D. and M.M. Kwatra, Human substance P receptor expressed in Chinese hamster ovary cells directly activates G(alpha q/11), G(alpha s), G(alpha o). FEBS Lett, 1998. 428(3): p. 291-4. 9. Khawaja, A.M. and D.F. Rogers, Tachykinins: receptor to effector. Int J Biochem Cell Biol, 1996. 28(7): p. 721-38. 10. Fong, T.M., et al., Differential activation of intracellular effector by two isoforms of human neurokinin-1 receptor. Mol Pharmacol, 1992. 41(1): p. 24-30. 11. Lai, J.P., et al., Differences in the length of the carboxyl terminus mediate functional properties of neurokinin-1 receptor. Proc Natl Acad Sci U S A, 2008. 105(34): p. 12605-10. 12. Smirnova, O.V. and R.L. Bogorad, Short forms of membrane receptors: generation and role in hormonal signal transduction. Biochemistry (Mosc), 2004. 69(4): p. 351-63. 13. Shen, K.Z. and R.A. North, Substance P opens cation channels and closes potassium channels in rat locus coeruleus neurons. Neuroscience, 1992. 50(2): p. 345-53. 14. Lu, B., et al., Peptide neurotransmitters activate a cation channel complex of NALCN and UNC-80. Nature, 2009. 457(7230): p. 741-4. 15. Jafri, M.S. and D. Weinreich, Substance P hyperpolarizes vagal sensory neurones of the ferret. J Physiol, 1996. 493 ( Pt 1): p. 157-66. 16. Kakehata, S., N. Akaike, and T. Takasaka, Substance P decreases the non-selective cation channel conductance in dissociated outer hair cells of guinea pig cochlea. Ann N Y Acad Sci, 1993. 707: p. 476-9. 17. Lin, C.C., et al., An antinociceptive role for substance P in acid-induced chronic muscle pain. Proc Natl Acad Sci U S A, 2012. 109(2): p. E76-83. 18. Huang, D., et al., Redox-Dependent Modulation of T-Type Ca(2+) Channels in Sensory Neurons Contributes to Acute Anti-Nociceptive Effect of Substance P. Antioxid Redox Signal, 2016. 25(5): p. 233-51. 19. Rameshwar, P., P. Gascon, and D. Ganea, Immunoregulatory effects of neuropeptides. Stimulation of interleukin-2 production by substance p. J Neuroimmunol, 1992. 37(1-2): p. 65-74. 20. Ji, R.R., et al., Central sensitization and LTP: do pain and memory share similar mechanisms? Trends Neurosci, 2003. 26(12): p. 696-705. 21. Holzer, P., Neurogenic vasodilatation and plasma leakage in the skin. Gen Pharmacol, 1998. 30(1): p. 5-11. 22. Otsuka, M. and K. Yoshioka, Neurotransmitter functions of mammalian tachykinins. Physiol Rev, 1993. 73(2): p. 229-308. 23. Russell, I.J., et al., Elevated cerebrospinal fluid levels of substance P in patients with the fibromyalgia syndrome. Arthritis Rheum, 1994. 37(11): p. 1593-601. 24. Vaeroy, H., et al., Elevated CSF levels of substance P and high incidence of Raynaud phenomenon in patients with fibromyalgia: new features for diagnosis. Pain, 1988. 32(1): p. 21-6. 25. Rupniak, N.M. and M.S. Kramer, Discovery of the antidepressant and anti-emetic efficacy of substance P receptor (NK1) antagonists. Trends Pharmacol Sci, 1999. 20(12): p. 485-90. 26. Rao, S.G., Current progress in the pharmacological therapy of fibromyalgia. Expert Opin Investig Drugs, 2009. 18(10): p. 1479-93. 27. Jensen, D.D., et al., Neurokinin 1 receptor signaling in endosomes mediates sustained nociception and is a viable therapeutic target for prolonged pain relief. Sci Transl Med, 2017. 9(392). 28. Wolfe, F., et al., The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum, 1995. 38(1): p. 19-28. 29. McBeth, J. and K. Jones, Epidemiology of chronic musculoskeletal pain. Best Pract Res Clin Rheumatol, 2007. 21(3): p. 403-25. 30. Vincent, A., et al., Prevalence of fibromyalgia: a population-based study in Olmsted County, Minnesota, utilizing the Rochester Epidemiology Project. Arthritis Care Res (Hoboken), 2013. 65(5): p. 786-92. 31. Dadabhoy, D., et al., Biology and therapy of fibromyalgia. Evidence-based biomarkers for fibromyalgia syndrome. Arthritis Res Ther, 2008. 10(4): p. 211. 32. Stratz, T., et al., Influence of tropisetron on the serum substance P levels in fibromyalgia patients. Scand J Rheumatol Suppl, 2004. 119: p. 41-3. 33. Sluka, K.A., A. Kalra, and S.A. Moore, Unilateral intramuscular injections of acidic saline produce a bilateral, long-lasting hyperalgesia. Muscle Nerve, 2001. 24(1): p. 37-46. 34. Sharma, N.K., et al., Acidic saline-induced primary and secondary mechanical hyperalgesia in mice. J Pain, 2009. 10(12): p. 1231-41. 35. Liu, Y.T., et al., Acid-induced hyperalgesia and anxio-depressive comorbidity in rats. Physiol Behav, 2014. 131: p. 105-10. 36. Nishiyori, M., et al., Permanent relief from intermittent cold stress-induced fibromyalgia-like abnormal pain by repeated intrathecal administration of antidepressants. Mol Pain, 2011. 7: p. 69. 37. Frederickson, R.C., et al., Dual actions of substance P on nociception: possible role of endogenous opioids. Science, 1978. 199(4335): p. 1359-62. 38. Oehme, P., et al., Substance-P - Does It Produce Analgesia or Hyperalgesia. Science, 1980. 208(4441): p. 305-307. 39. Guan, J.S., et al., Interaction with vesicle luminal protachykinin regulates surface expression of delta-opioid receptors and opioid analgesia. Cell, 2005. 122(4): p. 619-31. 40. Hall, M.E. and J.M. Stewart, Substance P and behavior: opposite effects of N-terminal and C-terminal fragments. Peptides, 1983. 4(5): p. 763-8. 41. Skilling, S.R., D.H. Smullin, and A.A. Larson, Differential effects of C- and N-terminal substance P metabolites on the release of amino acid neurotransmitters from the spinal cord: potential role in nociception. J Neurosci, 1990. 10(4): p. 1309-18. 42. Wu, L.J., et al., Feed-forward inhibition: a novel cellular mechanism for the analgesic effect of substance P. Mol Pain, 2005. 1: p. 34. 43. Pedersen-Bjergaard, U., et al., Algesia and local responses induced by neurokinin A and substance P in human skin and temporal muscle. Peptides, 1989. 10(6): p. 1147-52. 44. Babenko, V.V., et al., Experimental human muscle pain induced by intramuscular injections of bradykinin, serotonin, and substance P. Eur J Pain, 1999. 3(2): p. 93-102. 45. Jensen, K., et al., Pain, tenderness, wheal and flare induced by substance-P, bradykinin and 5-hydroxytryptamine in humans. Cephalalgia, 1991. 11(4): p. 175-82. 46. Chen, W.N. and C.C. Chen, Acid mediates a prolonged antinociception via substance P signaling in acid-induced chronic widespread pain. Mol Pain, 2014. 10: p. 30. 47. Chen, C.C., et al., A role for ASIC3 in the modulation of high-intensity pain stimuli. Proc Natl Acad Sci U S A, 2002. 99(13): p. 8992-7. 48. Huang, N.K., et al., Neuroprotective principles from Gastrodia elata. J Nat Prod, 2007. 70(4): p. 571-4. 49. Huang, N.K., et al., A new drug design targeting the adenosinergic system for Huntington's disease. PLoS One, 2011. 6(6): p. e20934. 50. Lin, Y.W., et al., Identification and characterization of a subset of mouse sensory neurons that express acid-sensing ion channel 3. Neuroscience, 2008. 151(2): p. 544-57. 51. Sluka, K.A., et al., Chronic hyperalgesia induced by repeated acid injections in muscle is abolished by the loss of ASIC3, but not ASIC1. Pain, 2003. 106(3): p. 229-39. 52. Chen, W.N., et al., Roles of ASIC3, TRPV1, and NaV1.8 in the transition from acute to chronic pain in a mouse model of fibromyalgia. Mol Pain, 2014. 10: p. 40. 53. Lin, S.H., et al., Evidence for the involvement of ASIC3 in sensory mechanotransduction in proprioceptors. Nat Commun, 2016. 7: p. 11460. 54. Waldmann, R. and M. Lazdunski, H(+)-gated cation channels: neuronal acid sensors in the NaC/DEG family of ion channels. Curr Opin Neurobiol, 1998. 8(3): p. 418-24. 55. Xing, J., J. Lu, and J. Li, ASIC3 contributes to the blunted muscle metaboreflex in heart failure. Med Sci Sports Exerc, 2015. 47(2): p. 257-63. 56. Dib-Hajj, S.D., et al., From genes to pain: Na v 1.7 and human pain disorders. Trends Neurosci, 2007. 30(11): p. 555-63. 57. Rush, A.M., T.R. Cummins, and S.G. Waxman, Multiple sodium channels and their roles in electrogenesis within dorsal root ganglion neurons. J Physiol, 2007. 579(Pt 1): p. 1-14. 58. Theile, J.W. and T.R. Cummins, Recent developments regarding voltage-gated sodium channel blockers for the treatment of inherited and acquired neuropathic pain syndromes. Front Pharmacol, 2011. 2: p. 54. 59. Nishiyori, M., et al., Absence of morphine analgesia and its underlying descending serotonergic activation in an experimental mouse model of fibromyalgia. Neurosci Lett, 2010. 472(3): p. 184-7. 60. Hata, T., E. Itoh, and A. Kawabata, Changes in CNS levels of serotonin and its metabolite in SART-stressed (repeatedly cold-stressed) rats. Jpn J Pharmacol, 1991. 56(1): p. 101-4. 61. Omiya, Y., et al., Changes in analgesia-producing mechanism of repeated cold stress loading in mice. Pharmacol Biochem Behav, 2000. 65(2): p. 261-6. 62. Yu, Y.Q., et al., Electrophysiological identification of tonic and phasic neurons in sensory dorsal root ganglion and their distinct implications in inflammatory pain. Physiol Res, 2014. 63(6): p. 793-9. 63. Djouhri, L., et al., Partial nerve injury induces electrophysiological changes in conducting (uninjured) nociceptive and nonnociceptive DRG neurons: Possible relationships to aspects of peripheral neuropathic pain and paresthesias. Pain, 2012. 153(9): p. 1824-36. 64. Renganathan, M., T.R. Cummins, and S.G. Waxman, Contribution of Na(v)1.8 sodium channels to action potential electrogenesis in DRG neurons. J Neurophysiol, 2001. 86(2): p. 629-40. 65. Blair, N.T. and B.P. Bean, Roles of tetrodotoxin (TTX)-sensitive Na+ current, TTX-resistant Na+ current, and Ca2+ current in the action potentials of nociceptive sensory neurons. J Neurosci, 2002. 22(23): p. 10277-90. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/20725 | - |
dc.description.abstract | 先前的研究發現酸會造成物質P的釋放,進而導致肌肉的止痛作用,而一實驗室研發的止痛藥物T1-11被發現無法在第三型酸敏感通道剔除且經過週期性冷刺激小鼠上產生作用,又發現T1-11引起的向外電流可以被物質P受體的拮抗劑減低,因次我認為物質P的止痛作用會受到剔除第三型酸敏感通道影響,首先,我利用單一細胞逆轉錄聚合酶鏈反應探討第三型酸敏感通道與瞬態感受器陽離子通道V1與物質P是否共同表現在同一個肌肉傳入的背根神經節神經細胞,結果發現,部分第三型酸敏感通道與瞬態感受器陽離子通道V1都有與物質P共同表現在同一顆細胞,其結果說明第三型酸敏感通道與瞬態感受器陽離子通道V1都有可能造成物質P的釋放。我接下來利用電生理的方式檢驗物質P與T1-11引起的向外電流是否會受到少了第三型酸敏感通道影響,結果顯示,物質P所引起的向外電流的細胞比例以及電流大小並不會受到剔除第三型酸敏感通道的影響,然而,在未經過週期性冷刺激小鼠,T1-11所引起的向外電流比例會受到剔除第三型酸敏感通道而顯著下降,但經過週期性冷刺激小鼠不會受到影響。除此之外,我發現剔除第三型酸敏感通道會顯著增加肌肉傳入的背根神經節神經細胞產生動作電位的閥值,其代表著第三型酸敏感通道有控制細胞神經活性的功能。另一方面,物質P所引起的向外電流會因為經過週期性冷刺激而增加,其說明物質P所引起的內生性止痛作用會受到週期性冷刺激而增強。我同時也發現部分對物質P沒有反應的細胞,其動作電位的過衝率也會受到週期性冷刺激而增加,因為較大的過衝率一般被認為是痛覺細胞的神經特性,我認為經過週期性冷刺激的肌肉傳入的背根神經節細胞會產生可塑性變化而趨向於痛覺神經元的特性。總結,我發現在未經過週期性冷刺激小鼠中,第三型酸敏感通道會顯著降低T1-11肌肉肌肉傳入的背根神經節神經細胞引起的向外電流的比例,此結果可能為T1-11無法在剔除第三型酸敏感通道中產生作用的原因。 | zh_TW |
dc.description.abstract | Previous study demonstrated that acid trigger substance P (SP) release and produced antinociceptive effect in muscle nociceptors, by which SP specifically enhances M-type potassium current and attenuates ASIC3-induced inward current on most gastrocnemius muscle (GM) afferent dorsal root ganglion (DRG) neurons Furthermore, previous study also indicated that the analgesia effect of T1-11, an active ingredient from Gastrodia elata for pain management, is ineffective in ASIC3 KO mice after intermittent cold stress (ICS) treatment and T1-11-induced outward current can be attenuated by NK1 antagonist. Therefore, I aimed to probe whether ASIC3 contributes to SP-mediated antinociception. Firstly, I identified the molecular identity of muscle afferent DRG neurons by use of single cell RT-PCR. The co-expression of SP with ASIC3 or TRPV1 implied the possibility that ASIC3 and TRPV1 serve as the antinociceptive acid sensors that release SP. Besides, I aimed to know whether loss of ASIC3 affects SM-SP-, a synthesized peptide analog of SP, and T1-11-induced outward current (ISM-SP-O and IT1-11-O) in muscle afferent DRG neurons by use of whole-cell patch clamp recording. The result demonstrated that deletion of ASIC3 did not affect neuronal population and average peak current of ISM-SP-O. However, I found diminished neuronal population of IT1-11-O after loss of ASIC3 in naïve but not ICS-treated mice. Furthermore, I found increased action potential (AP) threshold after deletion of ASIC3 and revealed a role of ASIC3 in setting the AP threshold. On the other hand, increased average peak current of ISM-SP-O was found in muscle afferent DRG neurons after ICS treatment, which suggests an enhanced SP-mediated antinociception. Besides, elevated AP overshoot was observed after ICS treatment in a subset of neurons that do not respond to SM-SP. Because large overshoot has been implicated as a feature of nociceptors, elevated overshoot after ICS treatment may indicate a pronociceptive neuronal plasticity occurred in these neurons. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T03:00:30Z (GMT). No. of bitstreams: 1 ntu-106-R04b21009-1.pdf: 10648324 bytes, checksum: 54a390529dced89c527c3efb64483d67 (MD5) Previous issue date: 2017 | en |
dc.description.tableofcontents | 口試委員審定書 i
致謝 ii 摘要 iii Abstract v Contents vii List of figures ix List of tables x Chapter 1. Introduction 1 1-1. Substance p (SP) 1 1-1-1. History 1 1-1-3. SP-mediated signaling 2 1-1-4. SP-mediated ionic current 3 1-1-5. Function of SP 4 1-2. SP and pain 5 1-2-1. Overview 5 1-2-2. Fibromyalgia 6 1-2-3. Animal models of fibromyalgia 7 1-2-3-1. Dual acid injection model 7 1-2-3-2. Intermittent cold stress 8 1-3. SP-mediated antinociception 8 1-3-1. Overview 8 1-3-2. SP-mediated antinociception in muscle nociceptors 10 1-3-3. Acid sensing ion channel 3(ASIC3) 11 1-3-4. T1-11 12 1-4. The central hypothesis and the purpose of this thesis 13 Chapter 2. Materials and Methods 15 2-1. Mice 15 2-2. Intermittent cold stress (ICS) 15 2-3. Gastrocnemius muscle retrograde-trace 16 2-4. Dorsal root ganglion primary culture 16 2-5. Whole-cell patch-clamp recording 17 2-6. Single cell RT-PCR 19 2-6-1. Single cell RNA extraction 19 2-6-2. Reverse transcription 19 2-6-3. Nested PCR 20 2-7. Statistic analysis of data 20 Chapter 3. Result 22 3-1.Co-expression of SP with ASIC3 or TRPV1 in GM-afferent DRG neurons 22 3-2. No sex difference in ISM-SP-O in GM-afferent DRG neurons 23 3-3. ISM-SP-O and ASIC3-mediated current are highly co-expressed in GM-afferent DRG neurons 23 3-4. No alteration of ISM-SP-O after knockout of ASIC3 25 3-5. Decreased neuronal population displayed IT1-11-O after knockout of ASIC3 in naïve condition 25 3-6. Broader AP half width in male mice 27 3-7. Decreased neuronal excitability of GM-afferent DRG neurons either after ICS treatment or knockout of ASIC3 28 3-8. Alterations of AP profile of GM-afferent DRG neurons by loss of ASIC3 or after ICS treatment 29 Chapter 4. Discussion 30 4-1. SP co-expressed with ASIC3 or TRPV1 30 4-2. The effect of ISM-SP-O, IT1-11-O after knockout of ASIC3 30 4-3. Alterations of AP profile after knockout of ASIC3 32 4-4. The effect of ICS treatment on ISM-SP-O, IT1-11-O 34 4-5. Alterations of AP profile after ICS treatment 35 4-6. Conclusions 36 References 37 | |
dc.language.iso | en | |
dc.title | 物質P引起的止痛作用在肌肉痛覺神經細胞的電生理與分子特性 | zh_TW |
dc.title | Electrophysiological and molecular characteristics of SP-mediated antinociception in muscle nociceptors | en |
dc.type | Thesis | |
dc.date.schoolyear | 105-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 閔明源,嚴震東,陳建璋,孫維欣 | |
dc.subject.keyword | 物質P,T1-11,第三型酸敏感通道,瞬態感受器陽離子通道V1,肌肉傳入的背根神經節神經細胞,週期性冷刺激, | zh_TW |
dc.subject.keyword | substance P,T1-11,ASIC3,TRPV1,muscle afferent DRG neurons,ICS, | en |
dc.relation.page | 68 | |
dc.identifier.doi | 10.6342/NTU201701989 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2017-07-26 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 生命科學系 | zh_TW |
顯示於系所單位: | 生命科學系 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-106-1.pdf 目前未授權公開取用 | 10.4 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。