Peripheral ASIC3 activation involves in the late phase of CCI-induced mechanical allodynia by switching CGRP-positive population from small to large diameter neurons

、線上人數：9

、訪客IP：18.191.46.36

姓名	龔家騏(Chia-Chi Kung) 查詢紙本館藏	畢業系所	生命科學系
論文名稱	(Peripheral ASIC3 activation involves in the late phase of CCI-induced mechanical allodynia by switching CGRP-positive population from small to large diameter neurons)
檔案	[Endnote RIS 格式] [Bibtex 格式] [相關文章] [文章引用] [完整記錄] [館藏目錄] 至系統瀏覽論文 ( 永不開放)
摘要(中)	ASIC酸敏性離子通道是電壓閘門低感度控制型的陽離子通道，當細胞外氫離子濃度上升時會開啟。ASIC3第三型酸敏性離子通道大量存在背根神經節中。神經受傷會導致背根神經節興奮增加。經由鈣通道流入的鈣離子對疼痛的產生有關。有研究提出，隨著H+濃度的上升會催化ASIC3 通道對鈣離子的開啟。在我們實驗室先前的數據中顯示，ASIC3基因剃除小鼠在神經慢性壓迫性損傷(Chronic constriction injury , CCI)術後4至8周有機械痛覺過敏緩解的情形。因此，我試圖瞭解在神經慢性壓迫性損傷(CCI)小鼠背根神經節中，ASIC3的表現量、背根神經節神經元表現型的轉換、鈣離子分佈和神經痛之間的關係。結果顯示，在神經慢性壓迫性損傷術後，小鼠產生單側機械性和熱覺痛覺過敏、背根神經節中ASIC3表現量增加、背根神經節中小神經元損失增加及神經元鈣離子濃度和具CGRP陽性的神經元增加。在注射第三型酸敏性離子通道的阻斷劑APETx2後，背根神經節中神經元鈣濃度、具CGRP陽性的神經元、背根神經節中ASIC3表現量以及神經痛行為上痛覺過敏的情形都下降。因此，基於上述發現，我認為在神經痛發展的後期，背根神經節中ASIC3參與了具CGRP陽性表現型神經元的轉換，神經元中鈣離子濃度的調控及神經痛的表現有關。
摘要(英)	ASICs, acid-sensing ion channels, are distributed between the central nervous system and peripheral nervous system specifically, where ASIC3 displays the highest expression than other subunits in DRG neurons. ASICs are voltage-insensitive cationic channels that are activated by the reduction of extracellular pH. ASIC3 channels has been proposed to be opened by catalyzing the relief of Ca2+ blockade as the H+ concentration rises. Calcium is an intracellular messenger and calcium signaling play a key role in neuronal gene expression. Ca2+ currents within the DRG participate in the development of neuropathic pain. Our previous data showed that mechanical hyperalgesia in ASIC3 knockout mice was attenuated gradually during postoperative 4 to 8 weeks. Accordingly, I tried to know the relationship among ASIC3 expression, neuron phenotype switching and calcium distribution in DRGs of Chronic constriction injury (CCI) mice. Results revealed that unilateral mechanical and thermal hyperalgesia, upregulation of ASIC3, more small neuron loss, higher intracellular calcium concentration and switching CGRP positive neuron develop in mice of CCI model. After injection of APETx2, a specific ASIC3 blocker, significant reduction of intracellular calcium concentration, decrease in ASIC3 expression and CGRP expression in neurons are noted which is associated with attenuated behavioral hyperalgesia. Therefore, based on these findings, I infer that ASIC3 involves in neurons CGRP phenotype switching and neuron calcium modulation and neuropathic pain development.
關鍵字(中)	★ 酸敏性離子通道 ★ 神經慢性壓迫性損傷	關鍵字(英)	★ ASIC3 ★ CGRP ★ neuropathic pain
論文目次	Table of Contents 中文摘要 i Abstract ii Abbreviation iii Table of Contents iv List of Figures and Tables viii Chapter 1 General Introduction 1 1-1 Neuropathic pain 2 1-2 Wallerian degeneration and regeneration in neuropathic pain 3 1-3 ASIC3 and neuropathic pain 4 1-4 Calcium and pain 8 1-5 Neuron loss 11 1-6 ATF3 13 Chapter 2 Materials and Methods 15 2-1 Materials 16 2-1-1. Animals 16 2-1-2. Agents and constructs 16 2-2 Methods 17 2-2-1. Chronic constriction injury model 17 2-2-2. Mechanical test 17 2-2-3. Thermal test 18 2-2-4. Animal tissue preparation 18 2-2-5. RNA preparation, cDNA synthesis and quantitative PCR 18 2-2-6. Immunohistochemistry 19 2-2-7. Primary culture cell and calcium imaging assay 20 2-2-8. Electrophysiology (action potential recording) 22 2-2-9. Statistical analysis 23 Chapter 3 Increased number of CGRP-positive neurons involves in CCI-induced neuropathic pain 24 3-1 Introduction 25 3-2 Results 26 3-2-1. Chronic constriction injury induces mechanical allodynia, thermal hyperalgesia and upregulation of ASIC3 mRNA expression 26 3-2-2. Increase calcium concentration in larger neurons without isolectin B4 selection after CCI injury 26 3-2-3. CCI induced more neuron degeneration in PERI + small neurons and upregulation ATF3 expression in large neurons 28 3-2-4. Increased CGRP expression shifts to large neurons with time discrepancy ……..29 Chapter 4 Injection of ASIC3 antagonist, APETx2 relieves CCI-induced neuropathic pain via reducing CGRP-positive population in large diameter neurons 37 4-1 Introduction 38 4-2 Results 38 4-2-1. APETx2 reduces CCI-induced mechanical allodynia, thermal hyperalgesia and late ASIC3 expression 38 4-2-2. APETx2 inhibit large neurons calcium concentration in late phase mostly… 39 4-2-3. APETx2 reduce neuron degeneration, ATF3 expression and CGRP expression after CCI injury 40 4-2-4. Blocked signaling transmission induced by CCI is recovered by inhibition of ASIC3 in DRG 41 Chapter 5 Discussions and Conclusion 51 Chapter 6 References 54 Appendix 68 List of Figures and Tables Fig. 3-1 Chronic constriction injury induces mechanical allodynia, thermal hyperalgesia and upregulation of ASIC3 mRNA expression 30 Fig. 3-2 CCI induces increase of calcium in both isolectin B4 positive and negative neurons 31 Fig. 3-3 Increase of calcium distributes in different size of neurons following times after nerve injury 33 Fig. 3-4 DRG neurons degeneration happened following times after nerve injury 34 Fig. 3-5 CCI induces ATF3 increase in the large DRG neurons over times ……...35 Fig. 3-6 Increase of CGRP shifts to the large DRG neurons following times after nerve injury 36 Fig. 4-1 Intrathecal injection of ASIC3 blocker reduces CCI-induced mechanical allodynia and thermal hyperalgesia 43 Fig. 4-2 Intrathecal inhibition of ASIC3 expression inhibits calcium increasing in DRG after nerve injury 44 Fig. 4-3 Inhibition of ASIC3 reduces calcium levels in small and large neurons after nerve injury 45 Fig. 4-4 Inhibition of ASIC3 in DRG recovers neurons after nerve injury…...….. 46 Fig. 4-5 Increase of ATF3 in DRG neurons was reduced by inhibition of ASIC3 …..47 Fig. 4-6 Increase of CGRP in large cells was reduced by inhibition of ASIC3 in DRG 48 Fig. 4-7 Inhibition of ASIC3 in DRG recovers signaling transmission blocked by CCI 49 Table 2.1 Oligonucleotide primers used in RT-PCR experiments 77
參考文獻	Adalbert R, Morreale G, Paizs M, Siklós L, Coleman MP. Intra-axonal calcium changes after axotomy in wild-type and slow Wallerian degeneration axons. 2012. Neuroscience. 6;225:44-54. doi: 10.1016. Allen NJ and Attwell D. Modulation of ASIC channels in rat cerebellar Purkinje neurons by ischaemia-related signals. 2002. J. Physiol. 543:521-529. Averill S, Mcmahon SB, Clary DO, Reichardt LF, and Priestley JV. Immunocytochemical localization of trkA receptors in chemically identified subgroups of adult rat sensory neurons. 1995. Eur. J. Neurosci. 7:1484–1494. Babinski K, Catarsi S, Biagini G, and Seguela P. Mammalian ASIC2a and ASIC3 subunits co-assemble into heteromeric proton-gated channels sensitive to Gd3+. 2000. J. Biol. Chem. 275:28519–28525. Bartzokis G, Cummings JL and Sultzer D. White matter structural integrity in healthy aging adults and patients with Alzheimer disease. 2003. Arch Neurol. 60:393–398. Benson CJ, Xie J, Wemmie JA, Price MP, Henss JM, Welsh MJ, and Snyder PM. Heteromultimers of DEG/ENaC subunits form H+-gated channels in mouse sensory neurons. 2002. Proc. Natl. Acad. Sci. 99:2338–2343. Bennett GJ, Xie YK. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. 1988. Pain.33:87–107. Berridge MJ, Lipp P, Bootman MD, The versatility and universality of calcium signaling. 2000. Nat. Rev. Mol. Cell Biol. 1:11–21. Berridge MJ, Bootman MD, and Roderick HL, Calcium signalling: dynamics, homeostasis and remodelling, 2003. Nat. Rev. Mol. Cell Biol. 4:517–529. Bernardi P, and Stockum S, The permeability transition pore as a Ca(2+) release channel: new answers to an old question. 2012. Cell Calcium. 52:22–27. Blanchard MG, Rash LD, and Kellenberger S. Inhibition of voltage-gated Na+ currents in sensory neurones by the sea anemone toxin APETx2. 2012. Br. J. Pharmacol. 165: 2167-2177. Burnett MG, Zager EL. Pathophysiology of peripheral nerve injury: a brief review. 2004. Neurosurg Focus. 15;16(5):E1. doi: 10.3171/foc.2004.16.5.2. Bullens P, Daemen M, Kurvers H. Motor dysfunction and reflex sympathetic dystrophy. Bilateral motor denervation in an experimental model. 1998. Acta Orthop Belg. 64:218 –223 Cadiou H, Studer M, Jones NG, Smith ES, Ballard A, McMahon SB, and McNaughton PA. Modulation of acid-sensing ion channel activity by nitric oxide. 2007. J. Neurosci. 27:13251-13260. Callejo G, Castellanos A, Castany M, Gual A, Luna C, Acosta MC, Gallar J, Giblin JP, and Gasull X. Acid-sensing ion channels detect moderate acidifications to induce ocular pain. 2015. Pain 156:483-495. Carlton SM, Dougherty PM, Pover CM, Coggeshall RE. Neuroma formation and numbers of axons in a rat model of experimental peripheral neuropathy. 1991. Neurosci Lett. 131:88 –92. Casals-Diaz L, Vivo M, and Navarro X. Nociceptive responses and spinal plastic changes of afferent C-fibers in three neuropathic pain models induced by sciatic nerve injury in the rat. 2009. Experimental Neurology. 217:84-95. Chen CC, Zimmer A, Sun WH, Hall J, Brownstein MJ, and Zimmer A. A role for ASIC3 in the modulation of high-intensity pain stimuli. 2002. Proc Natl Acad Sci. 99:8992–8997. Chen M, He H, Zhan S, Krajewski S, Reed JC, and Gottlieb RA. Bid is cleaved by calpain to an active fragment in vitro and during myocardial ischemia/reperfusion. 2001. J. Biol. Chem. 276:30724–30728. Chipuk JE, Moldoveanu T, Llambi F, Parsons MJ, and Green DR. The BCL-2 family reunion. 2010. Mol. Cell. 37:299–310. De Logu F., Nassini R., Landini L., Geppetti P. (2018) Pathways of CGRP Release from Primary Sensory Neurons. In: Brain S., Geppetti P. (eds) Calcitonin Gene-Related Peptide (CGRP) Mechanisms. Handbook of Experimental Pharmacology, vol 255. Springer, Cham. https://doi.org/10.1007/164_2018_145 Deval E, Salinas M, Baron A, Lingueglia E, and Lazdunski M. ASIC2b-dependent regulation of ASIC3, an essential acid-sensing ion channel subunit in sensory neurons via the partner protein PICK-1.2004. J. Biol. Chem. 279:19531-19539. Deval E, Noel J, Lay N, Alloui A, Diochot S, Friend V, Jodar M, Lazdunski M, and Lingueglia E. ASIC3, a sensor of acidic and primary inflammatory pain. 2008. EMBO J. 27:3047–3055. Devor M, Seltzer Z. Pathophysiology of damaged nerves in relation to chronic pain. In: Textbook of Pain (4th ed.), edited by Wall PD and Melzack R. London: Churchill Livingston, 1999, p. 129–164. Djouhri L, Lawson SN. Abeta-fiber nociceptive primary afferent neurons: a review of incidence and properties in relation to other afferent A-fiber neurons in mammals. 2004. Brain Res. Rev. 46 (2):131–145. Dubois C, Vanden Abeele F, and Prevarskaya N, Targeting apoptosis by the remodelling of calcium-transporting proteins in cancerogenesis. 2013. FEBS J. 280:5500–5510. Eisenach JC, Ma W. Chronic constriction injury of sciatic nerve induces the up-regulation of descending inhibitory noradrenergic innervation to the lumbar dorsal horn of mice. 2003. Brain Res. 970:110 –118 Fagoe ND, Attwell CL, Kouwenhoven D, Verhaagen J, and Mason MRJ. Overexpression of ATF3 or the combination of ATF3, c-Jun, STAT3 and Smad1 promotes regeneration of the central axon branch of sensory neurons but without synergistic effects. 2015. Human Molecular Genetics. 24:6788-6800. Fyfe GK, Quinn A, and Canessa CM. Structure and function of the Mec-ENaC family of ion channels. 1998. Semin. Nephrol. 18:138–151. Gabay E and Tal M. Pain behavior and nerve electrophysiology in the CCI model of neuropathic pain. 2004. Pain.110:354-60. García-Añoveros J, Derfler B, Neville-Golden J, Hyman BT, and Corey DP. BNaC1 and BNaC2 constitute a new family of human neuronal sodium channels related to degenerins and epithelial sodium channels.1997. PNAS. 94:1459–1464. Gillardon F, Klimaschewski L, Wickert H, Krajewski S, Reed JC, and Zimmermann M. Expression pattern of candidate cell death effector proteins Bax, Bcl-2, Bcl-X, and c-Jun in sensory and motor neurons following sciatic nerve transection in the rat. 1996. Brain Res. 739:244–250. Giorgi C, Baldassari F, Bononi A, Bonora M, Marchi ED, Marchi S, Missiroli S, Patergnani S, Rimessi A, Suski JM, Wieckowski MR, and Pinton P, Mitochondrial Ca(2+) and apoptosis. 2012. Cell Calcium. 52:36–43. Ghosh-Roy, A., Wu, Z., Goncharov, A., Jin, Y. and Chisholm, A.D. Calcium and cyclic AMP promote axonal regeneration in Caenorhabditis elegans and require DLK-1 kinase. 2010. J. Neurosci. 30, 3175–3183 Gilchrist, M., Thorsson, V., Li, B., Rust, A. G., Korb, M., Roach, J. C., Kennedy, K., Hai, T., Bolouri, H., and Aderem, A. (2006). Systems biology approaches identify ATF3 as a negative regulator of Toll-like receptor 4. Nature 441, 173–178. Hai T and Hartman MG. The molecular biology and nomenclature of the activating transcription factor/cAMP responsive element binding family of transcription factors: acitvating transcription factor proteins and homeostasis. 2001. Gene. 273:1-11. Hajnoczky G, Csordas G, Das S, Garcia-Perez C, Saotome M, Roy SS, and Yi M, Mitochondrial calcium signalling and cell death: approaches for assessing the role of mitochondrial Ca2+ uptake in apoptosis. 2006. Cell Calcium 40:553–560. Hammond DL, Ackerman L, Holdsworth R, and Elzey B. Effects of spinal nerve ligation on immunohistochemically identified neurons in the L4 and L5 dorsal root ganglia of the rat. 2004. J Comp Neurol. 475:575–589. Hattori T, Chen J, Harding AM, Price MP, Lu Y, Abboud FM, and Benson CJ. ASIC2a and ASIC3 heteromultimerize to form pH-sensitive channels in mouse cardiac dorsal root ganglia neurons. 2009. Circ. Res. 105:279–286. Hartlehnert M, Derksen A, Hagenacker T, Kindermann D, Schafers M, Pawlak M, Kieseier BC, and Horste GM. Schwann cells promote post-traumatic nerve inflammation and neuropathic pain through MHC calls II. 2017. Scientific Reports. 7:12158. Hildebrand C, Remahl S, Persson H, and Bjartmar C. Myelinated nerve fibers in the CNS. 1993. Prog Neurobiol. 40:319–84. Hogan Q, Lirk P, Poroli M, et al. Restoration of calcium influx corrects membrane hyperexcitability in injured rat dorsal root ganglion neurons. 2008. Anesth Analg. 107:1045–51. Hu W, Chen FH, , Zhang CC, Lin MY. Blockade of acid-sensing ion channels protects articular chondrocytes from acid-induced apoptotic injury. 2012. Inflamm Res. 61(4):327-35. doi: 10.1007/s00011-011-0414-6. Immke DC and McCleskey EW. Protons open acid-sensing ion channels by catalyzing relief of Ca2+ blockade. 2003. Neuron. 37:75–84. Jasti J, Furukawa H, Gonzales EB, and Gouaux E. Structure of acid-sensing ion channel 1 at 1.9 A resolution and low pH. 2007. Nature. 449:316–323. Jagodic MM, Pathirathna S, Jevtovic-Todorovic V, Todorovic SM. Upregulation of the T-type calcium current in small rat sensory neurons after chronic constrictive injury of the sciatic nerve. 2008. J Neurophysiol ; 99(6):3151-6. doi: 10.1152/jn.01031.2007. Kamiya H, Zhang W, and Sima AA. Apoptotic stress is counterbalanced by survival elements preventing programmed cell death of DRGs in subacute type 1 diabetic BB/Wor-rats. 2005. Diabetes. 54:3288–3295. Kamiya H, Zhang W, and Sima AA. Degeneration of the Golgi and neuronal loss in dorsal root ganglia in diabetic BioBreeding/Worcester rats. 2006. Diabetologia. 49:2763-2774. Karczewski, J, Spencer RH, Garsky VM, Liang A, Leitl MD, Cato MJ, Cook SP, Kane S, and Urban MO. Reversal of acid-induced and inflammatory pain by the selective ASIC3 inhibitor, APETx2. 2010. Br. J. Pharmacol. 161:950–960. Kuniyoshi K, Ohtori S, Ochiai N, Murata R, Matsudo T, Yamada T, et al. Characteristics of sensory DRG neurons innervating the wrist joint in rats. 2007. Eur. J. Pain. 11:323–328. Kung CC, Huang YC, Hung TY, Teng CY, Lee TY, Sun WH. Deletion of Acid-Sensing Ion Channel 3 Relieves the Late Phase of Neuropathic Pain by Preventing Neuron Degeneration and Promoting Neuron Repair. 2020. Cells. 9(11):2355. doi: 10.3390/cells9112355. Krishtal O. The ASICs: signaling molecules? Modulators? 2003. Trends Neurosci. 26:477–483 Kroemer G, Galluzzi L, and Brenner C, Mitochondrial membrane permeabilization in cell death. 2007. Physiol Rev. 87:99–163. Lirk P, Poroli M, Rigaud M, et al. Modulators of calcium influx regulate membrane excitability in rat dorsal root ganglion neurons. 2008. Anesth Analg. 107:673–685. Liu CN, Devor M. Tactile allodynia in the absence of C-fiber activation: altered firing properties of DRG neurons following spinal nerve injury. 2000. Pain 85 (3): 503–521. Liu X, Chung K, Chung JM. Ectopic discharges and adrenergic sensitivity of sensory neurons after spinal nerve injury. 1999 Brain Res 849: 244–247. Lu SG, Zhang XL, Luo ZD, and Gold MS. Persistent inflammation alters the density and distribution of voltage-activated calcium channels in subpopulations of rat cutaneous DRG neurons. 2010. Pain. 151:633–43. Lundberg JM, Franco-Cereceda A, Alving K, Delay-Goyet P, Lou YP. Release of calcitonin gene-related peptide from sensory neurons. 1992. Ann N Y Acad Sci 657:187–193 Lundborg G. A 25-year perspective of peripheral nerve surgery: evolving neuroscientic concepts and chemical significance.2000. JHSA. 25:391-414. Luo W, Enomoto H, Rice FL, Milbrandt J, and Ginty DD. Molecular identification of rapidly adapting mechanoreceptors and their developmental dependence on ret signaling. 2009. Neuron. 64:841–856. McLachlan EM, Janig W, Devor M, Michaelis M. Peripheral nerve injury triggers noradrenergic sprouting within dorsal root ganglia.1993.Nature.363:543–546 Micheau O and Tschopp J. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. 2003. Cell. 114:181–190. Micheli L, Cialdai F, Pacini A, Branca JJV, Morbidelli L, Ciccone V, Lucarini E, Ghelardini C, Monici M, and Mannelli LDC. Effect of NIR laser therapy by MLS-Mis source against neuropathic pain in rats: in vivo and ex vivo analysis. 2019. Scientific Reports. 9:9297. Mogil JS, Breese NM, Witty MF, Ritchie J, Rainville ML, Ase A, Abbadi N, Stucky CL, and Séguéla P. Transgenic expression of a dominant-negative ASIC3 subunit leads to increased sensitivity to mechanical and inflammatory stimuli. 2005. J Neurosci. 25:9893–9901. Molliver DC, Radeke MJ, Feinstein SC, and Snider WD. Presence or absence of TrkA protein distinguishes subsets of small sensory neurons with unique cytochemical characteristics and dorsal horn projections. 1995. J. Comp. Neurol. 361:404–416. Molliver DC, Immke DC, Fierro L, Pare M, Rice FL, and McCleskey EW. ASIC3, an acid-sensing ion channel, is expressed in metaboreceptive sensory neurons. 2005. Mol. Pain. 1:35. Morishima N, Nakanishi K, Takenouchi H, Shibata T, and Yasuhiko Y, An endoplasmic reticulum stress-specific caspase cascade in apoptosis. Cytochrome c-independent activation of caspase-9 by caspase-12. 2002. J. Biol. Chem. 277:34287–34294. Nakagawa T, Zhu H, Morishima N, Li E, Xu J, Yankner BA, and Yuan J. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloidbeta. 2000. Nature. 403:98–103. Nieuwenhuys R, Tendokelaar HJ, and Nicholson C. Structure and organization of fibre system. 1999. The Central Nervous System of Vertebrates. Ch3. 113–57. Nitzan-Luques A, Devor M, Tal M. Genotype-selective phenotypic switch in primary afferent neurons contributes to neuropathic pain. 2011. Pain.;152(10):2413-26. doi: 10.1016/j. Nitzan-Luques A, Minert A, Devor M, Tal M. Dynamic genotype-selective "phenotypic switching" of CGRP expression contributes to differential neuropathic pain phenotype. 2013. Exp Neurol. 250:194-204. doi: 10.1016/j. Noguchi K, et al. Alpha-CGRP and beta-CGRP mRNAs are differentially regulated in the rat spinal cord and dorsal root ganglion. 1990. Mol Brain Res. 1990. 7:299-304. Orrenius S, Zhivotovsky B, and Nicotera P. Regulation of cell death: the calciumapoptosis link. 2003 Nat. Rev. Mol. Cell Biol. 4:552–565. Parrado SG, Montalvan AF, Machleidt IA, Popp O, Bestvater F, Holloschi A, Knoch TA, Auerswald EA, Welsh K, Reed JC, Fritz H, FuentesPrior P, Spiess E, Salvesen GS, and Machleidt W, Ionomycin-activated calpain triggers apoptosis. A probable role for Bcl-2 family members. 2002. J. Biol. Chem. 277:27217–27226. Pedersen SF, Owsianik G, and Nilius B, TRP channels: an overview. 2005. Cell Calcium. 38:233–252. Pinton P, Giorgi C, Siviero R, Zecchini E, and Rizzuto R, Calcium and apoptosis: ER mitochondria Ca2+ transfer in the control of apoptosis. 2008. Oncogene. 27:6407–6418. Price MP, McIlwrath SL, Xie J, Cheng C, Qiao J, Tarr DE, Sluka KA, Brennan TJ, Lewin GR, and Welsh MJ. The DRASIC cation channel contributes to the detection of cutaneous touch and acid stimuli in mice. 2001. Neuron. 32:1071–1083. Ramer MS, and Bisby MA. Rapid sprouting of sympathetic axons in dorsal root ganglia of rats with a chronic constriction injury. 1997. Pain.70:237–244. Ramer MS, French DD, and Bisby MA. Wallerian degeneration is required for both neuropathic pain and sympathetic sprouting into the DRG. 1997. Pain. 72:71-78. Reichling DB and Levine JD. Critical role of nociceptor plasticity in chronic pain. 2009. Trends Neurosci. 32:611-618. Reimers C, et al. Identification of a cono-RFamide from the venom of Conus textile that targets ASIC3 and enhances muscle pain. 2017. PNAS. 114:3507-3515. Richard M. LoPachin, Ellen J. Lehning, Mechanism of Calcium Entry during Axon Injury and Degeneration. 1997. Toxicology and Applied Pharmacology. 143:233-244. Rishal, I. and Fainzilber, M. Axon–soma communication in neuronal injury. 2014. Nat. Rev. Neurosci. 15, 32–42 Rizzuto R, Stefani DD, Raffaello A, and Mammucari C. Mitochondria as sensors and regulators of calcium signaling. 2012. Nat. Rev. Mol. Cell Biol. 13:566–578. Ruscheweyh R, Forsthuber L, Schoffnegger D, and Sandkühler J. Modification of classical neurochemical markers in identified primary afferent neurons with Aβ-, Aδ-, and C-fibers after chronic constriction injury in mice. 2007. J. Comp. Neurol. 502:325–336. Ryder C, McColl K, Zhong F, Distelhorst CW. Acidosis Promotes Bcl-2 Family-mediated Evasion of Apoptosis: INVOLVEMENT OF ACID-SENSING G PROTEIN-COUPLED RECEPTOR GPR65 SIGNALING TO MEK/ERK. 2012. J Biol Chem. 287:27863–27875 Salinas M, Lazdunski M, and Lingueglia E. Structural elements for the generation of sustained currents by the acid pain sensor ASIC3. 2009. J. Biol. Chem. 284:31851–31859. Sant’Anna MB, Kusuda R, Bozzo TA, Bassi GS, Alves Filho, JC, Cunha FQ, Ferreira SH, Souza GR, and Cunha TM. Medial plantar nerve ligation as a novel model of neuropathic pain in mice: pharmacological and molecular characterization. 2016. Scientific Reports. 6:26955. Scha fers M, Geis C, Svensson CI, Luo ZD, and Sommer C. Selective increase of tumour necrosis factor-alpha in injured and spared myelinated primary afferents after chronic constrictive injury of rat sciatic nerve. 2003. Eur J Neurosci. 17:791– 804. Scholz J and Woolf CJ. The neuropathic pain triad: neurons, immune cells and glia. 2007. Nat Neurosci. 10:1361-1368. Schuhmacher LN, Smith ES. Expression of acid-sensing ion channels and selection of reference genes in mouse and naked mole rat. 2016. Mol. Brain 9:97. Seedon HJ, editor. London:: Her Majesty’s Stationery Office; 1954. Peripheral nerve injuries Medical Research Council Special Report Series 282. Shaikh SA and Tajkhorshid E. Potential cation and H+ binding sites in acid sensing ion channel-1. 2008. Biophys. J. 95:5153–5164. Sherwood TW, Lee KG, Gormley MG, and Askwith CC. Heteromeric acid-sensing ion channels (ASICs) composed of ASIC2b and ASIC1a display novel channel properties and contribute to acidosis-induced neuronal death. 2011. J. Neurosci. 31:9723–9734. Shi TJ, Tandrup T, Bergman E, Xu ZQ, Ulfhake B, and Hökfelt T. Effect of peripheral nerve injury on dorsal root ganglion neurons in the C57 BL/6J mouse: marked changes both in cell numbers and neuropeptide expression. 2001. Neuroscience. 105:249-63. Shi JY, Liu GS, Lir LF, Kuo SM, Ton CH, Wen ZH, Tee R, Chen CH, Huang HT, Chen CL, Chao D, and Tai MH. Glial cell line-derived neurotrophic factor gene transfer exerts protective effect on axons in sciatic nerve following constriction-induced peripheral nerve injury. 2011. Human Gene Therapy. 22:721-731. Sima AA. New insights into the metabolic and molecular basis for diabetic neuropathy. 2003. Cell Mol Life Sci. 60:2445–2464. Sluka KA, Price MP, Breese NM, Stucky CL, Wemmie JA, and Welsh MJ. Chronic hyperalgesia induced by repeated acid injections in muscle is abolished by the loss of ASIC3, but not ASIC1. 2003. Pain. 106:229–39. Smith ES, Cadiou H, and McNaughton PA. Arachidonic acid potentiates acid-sensing ion channels in rat sensory neurons by a direct action. 2007. Neuroscience. 145:686-698. Smith E, Omerbašić D, Lechner SG, Anirudhan G, Lapatsina L, and Lewin GR. The molecular basis of acid insensitivity in the African naked mole-rat. 2011. Science. 334:1557-1560. Snider WD and McMahon SB. Tackling pain at the source: new ideas about nociceptors. 1998. Neuron. 20:629–632. Sommer C., Schafers M., Painful mononeuropathy in C57BL/Wld mice with delayed Wallerian degeneration: differential effects of cytokine production and nerve regeneration on thermal and mechanical hypersensitivity. 1998. Brain Res.78:4154–162. Sommer C, Lalonde A, Heckman HM, Rodriguez M, Myers RR. Quantitative neuropathology of a focal nerve injury causing hyperalgesia. 1995. J Neuropath Exp Neurol.54:635– 643. Steen KH, Reeh PW, Anton F, and Handwerker HO. Protons selectively induce lasting excitation and sensitization to mechanical stimulation of nociceptors in rat skin, in vitro. 1997. J. Neurosci. 12:86-95. Stevens CW, Kajander KC, Bennett GJ, Seybold VS. Bilateral and differential changes in spinal mu, delta and kappa opioid binding in rats with a painful, unilateral neuropathy.1991.Pain. 46:315–326. Sutherland SP, Benson CJ, Adelman JP, and McCleskey EW. Acid-sensing ion channel 3 matches the acid-gated current in cardiac ischemia-sensing neurons. 2001. PNAS. 98:711–716. Sunderland S. Rate of regeneration of I: sensory nerve fibers and II: motor fibers. 1947. Arch Neurol Psychiatry. 58:1–14. Tandrup T, Woolf CJ, and Coggeshall RE. Delay loss of small dorsal root ganglion cells after transection of the rat sciatica nerve. 2000. J Comp Neurol. 422:172-80. Tsiridou MP, Labrecque S, Godin AG, Koninck YD, and Wang F. Differential expression of acid–sensing ion channels in mouse primary afferents in Naïve and injured conditions. 2020. Front Cell Neurosci. 14:103. Uchiyama Y, Cheng CC, Danielson KG, et al. Expression of acid-sensing ion channel 3 (ASIC3) in nucleus pulposus cells of the intervertebral disc is regulated by p75NTR and ERK signaling. 2007. J Bone Miner Res. 22:1996–2006. Varon SS and Bunge RP. Trophic mechanisms in the peripheral nervous system. 1978. Annu Rev Neurosci. 1:327-361. Vigneswara V, Berry M, Logan A, and Ahmed Z. Caspase-2 is upregulated after sciatic nerve transection and its inhibition protects dorsal root ganglion neurons from apoptosis after serum withdrawal. 2013. PLoS One. 8:e57861. Waldmann R, Champigny G, Voilley N, Lauritzen I, and Lazdunski M. The mammalian degenerin MDEG, an amiloride-sensitive cation channel activated by mutations causing neurodegeneration in Caenorhabditis elegans. 1996. J. Biol. Chem. 271:10433–10436. Waldmann R, Bassilana F, de Weille J, Champigny G, Heurteaux C, and Lazdunski M. Molecular cloning of a non-inactivating proton-gated Na+ channel specific for sensory neurons. 1997. J. Biol. Chem. 272:20975-20978. Waldmann R, Champigny G, Bassilana F, Heurteaux C, and Lazdunski M. A proton-gated cation channel involved in acid-sensing. 1997. Nature. 386:173–177. Wang HG, Pathan N, Ethell IM, Krajewski S, Yamaguchi Y, Shibasaki F, McKeon F, Bobo T, Franke TF, and Reed JC. Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD. 1999. Science. 284:339–343. Wang Z., Gardell L.R., Porreca F., Pronociceptive actions of dynorphin maintain chronic neuropathic pain. 2001. J. Neurosci. 21: 1779–1786. Wemmie JA, Price MP, and Welsh MJ. Acid-sensing ion channels: advances, questions and therapeutic opportunities. 2006. Trends Neurosci. 29:578–586. Wiberg R, Novikova LN, and Kingham PJ. Evaluation of apoptotic pathways in dorsal root ganglion neurons following peripheral nerve injury. 2018. Neuroreport. 29:779–785. Willis WD and Coggeshall RE. Sensory Mechanisms of the Spinal Cord. 1991. Plenum Publishing Corporation, New York Wu WL, Lin YW, Min MY, and Chen CC. Mice lacking Asic3 show reduced anxiety-like behavior on the elevated plus maze and reduced aggression. 2010. Genes Brain Behav. 9:603–614. Xie J, Price MP, Wemmie JA, Askwith CC, and Welsh MJ. ASIC3 and ASIC1 mediate FMRFamide-related peptide enhancement of H+-gated currents in cultured dorsal root ganglion neurons. 2003. J. Neurophysiol. 89:2459–2465. Yan Q, Elliott J, and Snider WD. Brain-derived neurotrophic factor rescues spinal motor neurons from axotomy-induced cell death. 1992. Nature. 1360:753-755. Yan J, Edelmayer RM, Wei X, Felice MD, Porreca F, and Dussor G. Dural afferents express acid-sensing ion channels: A role for decreased meningeal pH in migraine headache. 2010. Pain. 152:106-113. Yermolaieva O, Leonard AS, Schnizler MK, Abboud FM, and Welsh MJ. Extracellular acidosis increases neuronal cell calcium by activating acid-sensing ion channel 1a. 2004. PNAS. 101:6752–6757. Ygge, J. Neuronal loss in lumbar dorsal root ganglia after proximal compared to distal sciatic nerve resection: a quantitative study in the rat. 1989. Brain Research. 478:193-195. Yin Q, Kemp GJ, and Frostick SP. Neurotrophins, neurones and peripheral nerve regeneration. 1998. J Hand Surg Br. 23:433-7. Zhang, S. J., Buchthal, B., Lau, D., Zou, M., Weiss, U., and Bading, H. A signaling cascade of nuclear calcium-CREB-ATF3 activated by synaptic NMDA receptors defines a gene repression module that protects against extrasynaptic NMDA receptor-induced neuronal cell death and ischemic brain damage. 2011.　J. Neurosci. 31, 4978–4990. Zhu YF, Henry JL. Excitability of Aβ sensory neurons is altered in an animal model of peripheral neuropathy. 2012. BMC Neurosci. 30;13:15. doi: 10.1186/1471-2202-13-15. Zhang MT, Wang Bing, Jia YN, Liu Ning, Ma PS, Gong SS, Niu Yang, Sun Tao, Li YX, Yu JQ. Neuroprotective effect of liquiritin against neuropathic pain inudced by chronic constriction injury of the sciatic nerve in mice. 2017. Biomedicine & Pharmacotherapy. 95:186-198
指導教授	孫維欣金秀連	審核日期	2021-1-11
推文	facebook plurk twitter funp google live udn HD myshare reddit netvibes friend youpush delicious baidu
網路書籤	Google bookmarks del.icio.us hemidemi myshare

博碩士論文 100284007 詳細資訊