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研究生: 莫罕
Mohamed Abbas Abdelhafez Abdelaziz
論文名稱: 脊髓星形膠質細胞在酸所誘導的痛覺初始反應和慢性肌肉疼痛中的角色
The role of spinal astrocytes in hyperalgesic priming in the acid-induced chronic muscle pain model
指導教授: 陳建璋
Chen, Chien-Chang
共同指導教授: 曾淑芬
Tzeng, Shun-Fen
學位類別: 博士
Doctor
系所名稱: 醫學院 - 跨領域神經科學國際博士學位學程
TIGP on The Interdisciplinary Neuroscience
論文出版年: 2023
畢業學年度: 111
語文別: 英文
論文頁數: 90
中文關鍵詞: 過敏性疼痛肌肉疼痛星形胶质细胞星形胶质细胞脊髓
外文關鍵詞: Hyperalgesic priming, Spinal cord, Muscle pain, Spinal astrocytes, D-serine
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  • Abstract. VIII CHAPTER 1: Introduction.1 1.1 General view about pain: the definition and neurobiology .1 1.2 The animal model for musculoskeletal pain and fibromyalgia 2 1.3 Acute pain conveys an opportunity for persistent pain..3 1.4 Characteristics of the hyperalgesic priming model. 5 1.5 The pain pathways and the laminar heterogeneity of the spinal cord 7 1.6 Role of astrocytes in physiological and pathological conditions of different types of pain.10 1.7 Astrocyte gliotransmitters play different roles in neuronal synaptic Regulation 11 CHAPTER 2: Significances, hypothesis, and study Aims 13 CHAPTER 3: Materials and methods.15 3.1 Animals.15 3.2 Model of acid-induced hyperalgesic priming and chronic muscle pain.15 3.3 Intrathecal administration of drugs 15 3.4 Western blot 16 3.5 Immunofluorescent staining. 17 3.6 Mice Chemogenetic manipulation and intraspinal virus injection 18 3.7 Measurement of spinal D-serine after first acid injection.20 3.8 Statistics 20 CHAPTER 4: Results 22 4.1 First acid-induced spinal pERK signals in VGLUT2+ neurons in spinal dorsal horn. 22 4.2 First acid injection-induced spinal astrocyte activation. 23 4.3 Pharmacological inhibition of astrocyte disrupted the priming formation after the first acid injection 24 4.4 Pharmacological activation of spinal astrocytes mimicked the first acid-induced priming and transient hyperalgesia..25 4.5 Chemogenetic manipulation of the spinal astrocytes ..26 4.5.1 The expression of spinal astrocyte-specific hM4D(Gi) or hM3D(Gq) 26 4.5.2 Chemogenetic activation of spinal astrocytes elicited hyperalgesic priming and transient hyperalgesia..27 4.5.3 Chemogenetic inhibition of the spinal astrocytes abolished the priming after the first acid injection.28 4.6 Spinal pERK inhibition reduces GFAP expression 28 4.7 Inhibition/knockdown of spinal astrocytic glutamate transporters blunted the hyperalgesic priming after the first acid injection 29 4.8 Spinal GLT-1 activation mimics the first acid-induced hyperalgesic priming without causing transient hyperalgesia...31 4.9 The first acid injection elevated the D-serine levels in the spinal cord 32 4.10 Astrocytic D-serine contributes to the priming signal induced after first acid injection or chemogenetic activation of the spinal astrocytes..32 4.11 P2X receptor in the spinal cord is not required for the hyperalgesic priming.34 CHAPTER 5: Discussion 35 CHAPTER 6: Conclusion. 41 CHAPTER 7: References. 42 CHAPTER 8: Tables and Figures 63

    1. Raja, S.N., et al., The revised International Association for the Study of Pain definition of pain: concepts, challenges, and compromises. Pain, 2020. 161(9): p. 1976-1982.
    2. Wood, J.N., et al., The Transition from Acute to Chronic Pain, in The Oxford Handbook of the Neurobiology of Pain. 2020. p. 678-701.
    3. Price, T.J., et al., Transition to chronic pain: opportunities for novel therapeutics. Nature Reviews Neuroscience, 2018. 19(7): p. 383-384.
    4. Wood, J.N., H.L.D.M. Willemen, and N. Eijkelkamp, Sensory Signaling Pathways in Inflammatory and Neuropathic Pain, in The Oxford Handbook of the Neurobiology of Pain. 2020. p. 608-658.
    5. Goldberg, D.S. and S.J. McGee, Pain as a global public health priority. BMC Public Health, 2011. 11: p. 770.
    6. Garland, E.L., Pain processing in the human nervous system: a selective review of nociceptive and biobehavioral pathways. Prim Care, 2012. 39(3): p. 561-71.
    7. Kuner, R., Central mechanisms of pathological pain. Nat Med, 2010. 16(11): p. 1258-66.
    8. Melzack, R. and P.D. Wall, Pain mechanisms: a new theory. Science, 1965. 150(3699): p. 971-9.
    9. Craig, A.D., Pain mechanisms: labeled lines versus convergence in central processing. Annu Rev Neurosci, 2003. 26: p. 1-30.
    10. Bennett, D.L.H. and C.G. Woods, Painful and painless channelopathies. The Lancet Neurology, 2014. 13(6): p. 587-599.
    11. Tiwari, V., et al., Activation of micro-delta opioid receptor heteromers inhibits neuropathic pain behavior in rodents. Pain, 2020. 161(4): p. 842-855.
    12. Liu, S., et al., CXCL13/CXCR5 signaling contributes to diabetes-induced tactile allodynia via activating pERK, pSTAT3, pAKT pathways and pro-inflammatory cytokines production in the spinal cord of male mice. Brain Behav Immun, 2019. 80: p. 711-724.
    13. Lesnak, J. and K.A. Sluka, Chronic non-inflammatory muscle pain: central and peripheral mediators. Curr Opin Physiol, 2019. 11: p. 67-74.
    14. D'Mello, R. and A.H. Dickenson, Spinal cord mechanisms of pain. Br J Anaesth, 2008. 101(1): p. 8-16.
    15. Sarzi-Puttini, P., et al., Fibromyalgia: an update on clinical characteristics, aetiopathogenesis and treatment. Nature Reviews Rheumatology, 2020. 16(11): p. 645-660.
    16. Granges, G. and G. Littlejohn, Pressure pain threshold in pain‐free subjects, in patients with chronic regional pain syndromes, and in patients with fibromyalgia syndrome. Arthritis & Rheumatism: Official Journal of the American College of Rheumatology, 1993. 36(5): p. 642-646.
    17. Tunks, E., et al., Tender points in fibromyalgia. Pain, 1988. 34(1): p. 11-19.
    18. Pomares, F.B., et al., Upregulation of cortical GABAA receptor concentration in fibromyalgia. Pain, 2020. 161(1): p. 74-82.
    19. Hudson, J.I. and H.G. Pope, The concept of affective spectrum disorder: relationship to fibromyalgia and other syndromes of chronic fatigue and chronic muscle pain. Baillière's clinical rheumatology, 1994. 8(4): p. 839-856.
    20. Neumann, L. and D. Buskila, Epidemiology of fibromyalgia. Current pain and headache reports, 2003. 7(5): p. 362-368.
    21. 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. 229-239.
    22. 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.
    23. Morris, R.G., Long-term potentiation and memory. Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences, 2003. 358(1432): p. 643-647.
    24. Jung, H., et al., Remote control of gene function by local translation. Cell, 2014. 157(1): p. 26-40.
    25. Yam, M.F., et al., General Pathways of Pain Sensation and the Major Neurotransmitters Involved in Pain Regulation. Int J Mol Sci, 2018. 19(8).
    26. Keller, A.F., et al., Transformation of the output of spinal lamina I neurons after nerve injury and microglia stimulation underlying neuropathic pain. Molecular pain, 2007. 3: p. 1744-8069-3-27.
    27. Brumovsky, P.R., VGLUTs in Peripheral Neurons and the Spinal Cord: Time for a Review. ISRN Neurol, 2013. 2013: p. 829753.
    28. Chapman, C.R., R.P. Tuckett, and C.W. Song, Pain and stress in a systems perspective: reciprocal neural, endocrine, and immune interactions. The Journal of Pain, 2008. 9(2): p. 122-145.
    29. Wiese, A.J. and T.L. Yaksh, Nociception and pain mechanisms. Handbook of veterinary pain management, 2015: p. 10-41.
    30. Ito, S., E. Okuda-Ashitaka, and T. Minami, Central and peripheral roles of prostaglandins in pain and their interactions with novel neuropeptides nociceptin and nocistatin. Neuroscience research, 2001. 41(4): p. 299-332.
    31. Silverman, H.A., et al., Involvement of neural transient receptor potential channels in peripheral inflammation. Frontiers in immunology, 2020. 11: p. 590261.
    32. Schug, S.A., et al., Acute pain management: scientific evidence, 2015. Medical Journal of Australia, 2016. 204(8): p. 315-317.
    33. Macintyre, P.E., et al., Acute pain management: scientific evidence. 2010: Australian and New Zealand College of Anaesthetists.
    34. Cervero, F., Visceral pain: mechanisms of peripheral and central sensitization. Annals of medicine, 1995. 27(2): p. 235-239.
    35. Carlton, S.M., et al., Peripheral and central sensitization in remote spinal cord regions contribute to central neuropathic pain after spinal cord injury. Pain®, 2009. 147(1-3): p. 265-276.
    36. Graven-Nielsen, T. and L. Arendt-Nielsen, Peripheral and central sensitization in musculoskeletal pain disorders: an experimental approach. Current rheumatology reports, 2002. 4(4): p. 313-321.
    37. Parada, C., et al., Transient attenuation of protein kinase Cϵ can terminate a chronic hyperalgesic state in the rat. Neuroscience, 2003. 120(1): p. 219-226.
    38. Reichling, D.B. and J.D. Levine, Critical role of nociceptor plasticity in chronic pain. Trends in neurosciences, 2009. 32(12): p. 611-618.
    39. Decosterd, I. and C.J. Woolf, Spared nerve injury: an animal model of persistent peripheral neuropathic pain. Pain, 2000. 87(2): p. 149-158.
    40. Woller, S.A., et al., Systemic TAK-242 prevents intrathecal LPS evoked hyperalgesia in male, but not female mice and prevents delayed allodynia following intraplantar formalin in both male and female mice: The role of TLR4 in the evolution of a persistent pain state. Brain Behav Immun, 2016. 56: p. 271-80.
    41. Kim, S.H. and J.M. Chung, An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain, 1992. 50(3): p. 355-363.
    42. Peirs, C., et al., Dorsal Horn Circuits for Persistent Mechanical Pain. Neuron, 2015. 87(4): p. 797-812.
    43. Varrassi, G., et al., Pharmacological treatment of chronic pain - the need for CHANGE. Curr Med Res Opin, 2010. 26(5): p. 1231-45.
    44. Liu, C.-N., et al., Tactile allodynia in the absence of C-fiber activation: altered firing properties of DRG neurons following spinal nerve injury. Pain, 2000. 85(3): p. 503-521.
    45. Kajander, K.C., et al., Dynorphin increases in the dorsal spinal cord in rats with a painful peripheral neuropathy. Peptides, 1990. 11(4): p. 719-728.
    46. Kandasamy, R. and T.J. Price, The pharmacology of nociceptor priming. Handb Exp Pharmacol, 2015. 227: p. 15-37.
    47. Aley, K., et al., Chronic hypersensitivity for inflammatory nociceptor sensitization mediated by the ε isozyme of protein kinase C. Journal of Neuroscience, 2000. 20(12): p. 4680-4685.
    48. Sluka, K., A. Kalra, and S. Moore, Unilateral intramuscular injections of acidic saline produce a bilateral, long‐lasting hyperalgesia. Muscle & Nerve: Official Journal of the American Association of Electrodiagnostic Medicine, 2001. 24(1): p. 37-46.
    49. Gregory, N.S., et al., Fatigue-enhanced hyperalgesia in response to muscle insult: induction and development occur in a sex-dependent manner. PAIN®, 2013. 154(12): p. 2668-2676.
    50. Quimby, L., S. Block, and G. Gratwick, Fibromyalgia: generalized pain intolerance and manifold symptom reporting. The Journal of Rheumatology, 1988. 15(8): p. 1264-1270.
    51. Cote, M.P., et al., Plasticity in ascending long propriospinal and descending supraspinal pathways in chronic cervical spinal cord injured rats. Front Physiol, 2012. 3: p. 330.
    52. Harrison, M., et al., Vertebral landmarks for the identification of spinal cord segments in the mouse. Neuroimage, 2013. 68: p. 22-9.
    53. Sidman, R.L., J.B. Angevine, and E.T. Pierce, Atlas of the mouse brain and spinal cord. 1971.
    54. Rexed, B., The cytoarchitectonic organization of the spinal cord in the cat. Journal of Comparative Neurology, 1952. 96(3): p. 415-495.
    55. Schoenen, J. and R. Faull, Spinal cord cyto and chemoarchitecture. The human nervous system. Elsevier Academic Press, 2004. 190: p. 228.
    56. Sengul, G. and C. Watson, Spinal Cord, in The Mouse Nervous System. 2012. p. 424-458.
    57. Bradesi, S., Role of spinal cord glia in the central processing of peripheral pain perception. Neurogastroenterol Motil, 2010. 22(5): p. 499-511.
    58. D'Mello, R. and A.H. Dickenson, Spinal cord mechanisms of pain. British journal of anaesthesia, 2008. 101(1): p. 8-16.
    59. Han, Z.-S., E.-T. Zhang, and A. Craig, Nociceptive and thermoreceptive lamina I neurons are anatomically distinct. Nature neuroscience, 1998. 1(3): p. 218-225.
    60. Wang, L., et al., Regulating nociceptive transmission by VGluT2-expressing spinal dorsal horn neurons. J Neurochem, 2018. 147(4): p. 526-540.
    61. Scherrer, G., et al., VGLUT2 expression in primary afferent neurons is essential for normal acute pain and injury-induced heat hypersensitivity. Proc Natl Acad Sci U S A, 2010. 107(51): p. 22296-301.
    62. Braz, J.M., et al., Parallel “pain” pathways arise from subpopulations of primary afferent nociceptor. Neuron, 2005. 47(6): p. 787-793.
    63. Fields, H.L. and A.I. Basbaum, Brainstem control of spinal pain-transmission neurons. Annual review of physiology, 1978. 40(1): p. 217-248.
    64. Todd, A.J., Neuronal circuitry for pain processing in the dorsal horn. Nat Rev Neurosci, 2010. 11(12): p. 823-36.
    65. Lu, Y. and E.R. Perl, A specific inhibitory pathway between substantia gelatinosa neurons receiving direct C-fiber input. Journal of Neuroscience, 2003. 23(25): p. 8752-8758.
    66. Lu, Y. and E.R. Perl, Modular organization of excitatory circuits between neurons of the spinal superficial dorsal horn (laminae I and II). Journal of Neuroscience, 2005. 25(15): p. 3900-3907.
    67. Uta, D., et al., TRPA1‐expressing primary afferents synapse with a morphologically identified subclass of substantia gelatinosa neurons in the adult rat spinal cord. European Journal of Neuroscience, 2010. 31(11): p. 1960-1973.
    68. Todd, A.J. and V. Lochhead, GABA-like immunoreactivity in type I glomeruli of rat substantia gelatinosa. Brain research, 1990. 514(1): p. 171-174.
    69. Todd, A. and J. McKenzie, GABA-immunoreactive neurons in the dorsal horn of the rat spinal cord. Neuroscience, 1989. 31(3): p. 799-806.
    70. Todd, A.J. and A.C. Sullivan, Light microscope study of the coexistence of GABA‐like and glycine‐like immunoreactivities in the spinal cord of the rat. Journal of Comparative Neurology, 1990. 296(3): p. 496-505.
    71. Todd, A., Immunohistochemical evidence that acetylcholine and glycine exist in different populations of GABAergic neurons in lamina III of rat spinal dorsal horn. Neuroscience, 1991. 44(3): p. 741-746.
    72. Kato, G., et al., Direct GABAergic and glycinergic inhibition of the substantia gelatinosa from the rostral ventromedial medulla revealed by in vivo patch-clamp analysis in rats. Journal of Neuroscience, 2006. 26(6): p. 1787-1794.
    73. Seifert, G., K. Schilling, and C. Steinhäuser, Astrocyte dysfunction in neurological disorders: a molecular perspective. Nature Reviews Neuroscience, 2006. 7(3): p. 194-206.
    74. <Neuron-glial interactions in the spinal cord for the amplification of chronic pain.pdf>.
    75. Gwak, Y.S., C.E. Hulsebosch, and J.W. Leem, Neuronal-Glial Interactions Maintain Chronic Neuropathic Pain after Spinal Cord Injury. Neural Plast, 2017. 2017: p. 2480689.
    76. Gao, Y.-J. and R.-R. Ji, Targeting astrocyte signaling for chronic pain. Neurotherapeutics, 2010. 7(4): p. 482-493.
    77. Wang, W., et al., Temporal changes of astrocyte activation and glutamate transporter‐1 expression in the spinal cord after spinal nerve ligation‐induced neuropathic pain. The Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology: Advances in Integrative Anatomy and Evolutionary Biology, 2008. 291(5): p. 513-518.
    78. Nakagawa, T. and S. Kaneko, Spinal astrocytes as therapeutic targets for pathological pain. J Pharmacol Sci, 2010. 114(4): p. 347-53.
    79. Zhou, J., et al., Activation of protein kinase A modulates trafficking of the human cardiac sodium channel in Xenopus oocytes. Circulation research, 2000. 87(1): p. 33-38.
    80. Kohro, Y., et al., Spinal astrocytes in superficial laminae gate brainstem descending control of mechanosensory hypersensitivity. Nat Neurosci, 2020. 23(11): p. 1376-1387.
    81. Wang, W., et al., Crosstalk between spinal astrocytes and neurons in nerve injury-induced neuropathic pain. PLoS One, 2009. 4(9): p. e6973.
    82. Barbour, B., H. Brew, and D. Attwell, Electrogenic glutamate uptake in glial cells is activated by intracellular potassium. Nature, 1988. 335(6189): p. 433-435.
    83. Rothstein, J.D., et al., Localization of neuronal and glial glutamate transporters. Neuron, 1994. 13(3): p. 713-725.
    84. Tao, F., et al., Evidence of neuronal excitatory amino acid carrier 1 expression in rat dorsal root ganglion neurons and their central terminals. Neuroscience, 2004. 123(4): p. 1045-1051.
    85. Tao, Y.-X., J. Gu, and R.L. Stephens Jr, Role of spinal cord glutamate transporter during normal sensory transmission and pathological pain states. Molecular Pain, 2005. 1: p. 1744-8069-1-30.
    86. Araque, A., G. Carmignoto, and P.G. Haydon, Dynamic signaling between astrocytes and neurons. Annual review of physiology, 2001. 63(1): p. 795-813.
    87. Covelo, A. and A. Araque, Neuronal activity determines distinct gliotransmitter release from a single astrocyte. Elife, 2018. 7.
    88. Wolosker, H., S. Blackshaw, and S.H. Snyder, Serine racemase: a glial enzyme synthesizing D-serine to regulate glutamate-N-methyl-D-aspartate neurotransmission. Proceedings of the National Academy of Sciences, 1999. 96(23): p. 13409-13414.
    89. Mothet, J.-P., et al., D-serine is an endogenous ligand for the glycine site of the N-methyl-D-aspartate receptor. Proceedings of the National Academy of Sciences, 2000. 97(9): p. 4926-4931.
    90. Zhou, X., et al., NMDA receptor-mediated excitotoxicity depends on the coactivation of synaptic and extrasynaptic receptors. Cell death & disease, 2013. 4(3): p. e560-e560.
    91. Sasabe, J., et al., d‐Serine is a key determinant of glutamate toxicity in amyotrophic lateral sclerosis. The EMBO journal, 2007. 26(18): p. 4149-4159.
    92. Lefèvre, Y., et al., Neuropathic pain depends upon D-serine co-activation of spinal NMDA receptors in rats. Neuroscience letters, 2015. 603: p. 42-47.
    93. Choi, S.-R., et al., Astrocyte D-serine modulates the activation of neuronal NOS leading to the development of mechanical allodynia in peripheral neuropathy. Molecular Pain, 2019. 15: p. 1744806919843046.
    94. Edens, J.L. and K.M. Gil, Experimental induction of pain: Utility in the study of clinical pain. Behavior Therapy, 1995. 26(2): p. 197-216.
    95. Woolf, C.J. and M.W. Salter, Neuronal plasticity: increasing the gain in pain. science, 2000. 288(5472): p. 1765-1768.
    96. Cohen, S.P. and J. Mao, Neuropathic pain: mechanisms and their clinical implications. Bmj, 2014. 348.
    97. Price, D.D., Psychological and neural mechanisms of the affective dimension of pain. Science, 2000. 288(5472): p. 1769-1772.
    98. Chen, W.H., et al., Spinal protein kinase C/extracellular signal-regulated kinase signal pathway mediates hyperalgesia priming. Pain, 2018. 159(5): p. 907-918.
    99. Ishibashi, M., K. Egawa, and A. Fukuda, Diverse Actions of Astrocytes in GABAergic Signaling. Int J Mol Sci, 2019. 20(12).
    100. Tawfik, V.L., et al., Induction of astrocyte differentiation by propentofylline increases glutamate transporter expression in vitro: heterogeneity of the quiescent phenotype. Glia, 2006. 54(3): p. 193-203.
    101. Watkins, L.R., E.D. Milligan, and S.F. Maier, Glial activation: a driving force for pathological pain. Trends in neurosciences, 2001. 24(8): p. 450-455.
    102. McMahon, S.B. and M. Malcangio, Current challenges in glia-pain biology. Neuron, 2009. 64(1): p. 46-54.
    103. Gao, Y.-J. and R.-R. Ji, Chemokines, neuronal–glial interactions, and central processing of neuropathic pain. Pharmacology & therapeutics, 2010. 126(1): p. 56-68.
    104. Ohmichi, M., et al., Activated spinal astrocytes are involved in the maintenance of chronic widespread mechanical hyperalgesia after cast immobilization. Molecular pain, 2014. 10: p. 1744-8069-10-6.
    105. Ji, R.-R., C.R. Donnelly, and M. Nedergaard, Astrocytes in chronic pain and itch. Nature Reviews Neuroscience, 2019. 20(11): p. 667-685.
    106. Lu, H.J. and Y.J. Gao, Astrocytes in Chronic Pain: Cellular and Molecular Mechanisms. Neurosci Bull, 2023. 39(3): p. 425-439.
    107. Adamsky, A., et al., Astrocytic Activation Generates De Novo Neuronal Potentiation and Memory Enhancement. Cell, 2018. 174(1): p. 59-71 e14.
    108. Brumovsky, P.R., et al., Expression of vesicular glutamate transporters type 1 and 2 in sensory and autonomic neurons innervating the mouse colorectum. Journal of Comparative Neurology, 2011. 519(16): p. 3346-3366.
    109. Wang, Y., et al., Expression of GFAP in rat brain stem astrocytes induced by stomachic nociception and relationship to neurons. Zhongguo Zuzhi Huaxue He Xibao Huaxue Zazhi, 2001. 10: p. 219-223.
    110. Sweitzer, S., et al., Acute peripheral inflammation induces moderate glial activation and spinal IL-1β expression that correlates with pain behavior in the rat. Brain research, 1999. 829(1-2): p. 209-221.
    111. Duan, B., L. Cheng, and Q. Ma, Spinal circuits transmitting mechanical pain and itch. Neuroscience bulletin, 2018. 34: p. 186-193.
    112. Ji, R.-R., A. Chamessian, and Y.-Q. Zhang, Pain regulation by non-neuronal cells and inflammation. Science, 2016. 354(6312): p. 572-577.
    113. Lee, S., et al., Channel-mediated tonic GABA release from glia. Science, 2010. 330(6005): p. 790-796.
    114. Sahlender, D.A., I. Savtchouk, and A. Volterra, What do we know about gliotransmitter release from astrocytes? Philosophical Transactions of the Royal Society B: Biological Sciences, 2014. 369(1654): p. 20130592.
    115. Stephenson, J.L. and M.R. Byers, GFAP immunoreactivity in trigeminal ganglion satellite cells after tooth injury in rats. Experimental neurology, 1995. 131(1): p. 11-22.
    116. Liu, B., et al., Spinal astrocytic activation contributes to mechanical allodynia in a rat model of cyclophosphamide-induced cystitis. Mol Pain, 2016. 12.
    117. Ji, R.-R., et al., Possible role of spinal astrocytes in maintaining chronic pain sensitization: review of current evidence with focus on bFGF/JNK pathway. Neuron glia biology, 2006. 2(4): p. 259-269.
    118. Gao, Y.J., L. Zhang, and R.R. Ji, Spinal injection of TNF‐α‐activated astrocytes produces persistent pain symptom mechanical allodynia by releasing monocyte chemoattractant protein‐1. Glia, 2010. 58(15): p. 1871-1880.
    119. Zhang, L., et al., TNF-alpha contributes to spinal cord synaptic plasticity and inflammatory pain: distinct role of TNF receptor subtypes 1 and 2. PAIN®, 2011. 152(2): p. 419-427.
    120. Julius, D. and A.I. Basbaum, Molecular mechanisms of nociception. Nature, 2001. 413(6852): p. 203-210.
    121. Youn, D.h., H. Wang, and S.J. Jeong, Exogenous tumor necrosis factor‐α rapidly alters synaptic and sensory transmission in the adult rat spinal cord dorsal horn. Journal of neuroscience research, 2008. 86(13): p. 2867-2875.
    122. Kawasaki, Y., et al., Cytokine mechanisms of central sensitization: distinct and overlapping role of interleukin-1β, interleukin-6, and tumor necrosis factor-α in regulating synaptic and neuronal activity in the superficial spinal cord. Journal of neuroscience, 2008. 28(20): p. 5189-5194.
    123. Ji, R.-R., et al., Central sensitization and LTP: do pain and memory share similar mechanisms? Trends in neurosciences, 2003. 26(12): p. 696-705.
    124. Xu, J.-T., et al., The role of tumor necrosis factor-alpha in the neuropathic pain induced by Lumbar 5 ventral root transection in rat. Pain, 2006. 123(3): p. 306-321.
    125. Hao, S., et al., Gene transfer to interfere with TNFα signaling in neuropathic pain. Gene therapy, 2007. 14(13): p. 1010-1016.
    126. DeLeo, J.A., R.W. Colburn, and A.J. Rickman, Cytokine and growth factor immunohistochemical spinal profiles in two animal models of mononeuropathy. Brain research, 1997. 759(1): p. 50-57.
    127. Prescott, S.A., Q. Ma, and Y. De Koninck, Normal and abnormal coding of somatosensory stimuli causing pain. Nat Neurosci, 2014. 17(2): p. 183-91.
    128. Roth, B.L., DREADDs for neuroscientists. Neuron, 2016. 89(4): p. 683-694.
    129. Sloan, S.A. and B.A. Barres, The detrimental role of glial acidification during ischemia. Neuron, 2014. 81(2): p. 221-223.
    130. Bezzi, P. and A. Volterra, A neuron–glia signalling network in the active brain. Current opinion in neurobiology, 2001. 11(3): p. 387-394.
    131. Nishiyama, H., et al., Glial protein S100B modulates long-term neuronal synaptic plasticity. Proceedings of the National Academy of Sciences, 2002. 99(6): p. 4037-4042.
    132. Newman, L.A., D.L. Korol, and P.E. Gold, Lactate produced by glycogenolysis in astrocytes regulates memory processing. PloS one, 2011. 6(12): p. e28427.
    133. Tadi, M., et al., Learning-induced gene expression in the hippocampus reveals a role of neuron-astrocyte metabolic coupling in long term memory. PloS one, 2015. 10(10): p. e0141568.
    134. Gerlai, R., et al., Overexpression of a calcium-binding protein, S100 beta, in astrocytes alters synaptic plasticity and impairs spatial learning in transgenic mice. Learning & Memory, 1995. 2(1): p. 26-39.
    135. Yaster, M., et al., Effect of inhibition of spinal cord glutamate transporters on inflammatory pain induced by formalin and complete Freund's adjuvant. The Journal of the American Society of Anesthesiologists, 2011. 114(2): p. 412-423.
    136. Niederberger, E., et al., The glutamate transporter GLAST is involved in spinal nociceptive processing. Biochemical and biophysical research communications, 2006. 346(2): p. 393-399.
    137. Weng, H.-R., J. Chen, and J. Cata, Inhibition of glutamate uptake in the spinal cord induces hyperalgesia and increased responses of spinal dorsal horn neurons to peripheral afferent stimulation. Neuroscience, 2006. 138(4): p. 1351-1360.
    138. Basbaum, A., History of Spinal Cord “Pain” Pathways Including the Pathways Not Taken. Frontiers in Pain Research, 2022. 3.
    139. Chen, S.-R. and H.-L. Pan, Distinct roles of group III metabotropic glutamate receptors in control of nociception and dorsal horn neurons in normal and nerve-injured Rats. Journal of Pharmacology and Experimental Therapeutics, 2005. 312(1): p. 120-126.
    140. Zhang, H.-M., S.-R. Chen, and H.-L. Pan, Effects of activation of group III metabotropic glutamate receptors on spinal synaptic transmission in a rat model of neuropathic pain. Neuroscience, 2009. 158(2): p. 875-884.
    141. Maki, R., M. Robinson, and M. Dichter, The glutamate uptake inhibitor L-trans-pyrrolidine-2, 4-dicarboxylate depresses excitatory synaptic transmission via a presynaptic mechanism in cultured hippocampal neurons. Journal of Neuroscience, 1994. 14(11): p. 6754-6762.
    142. Rao, V.L.R., et al., Antisense knockdown of the glial glutamate transporter GLT-1, but not the neuronal glutamate transporter EAAC1, exacerbates transient focal cerebral ischemia-induced neuronal damage in rat brain. Journal of Neuroscience, 2001. 21(6): p. 1876-1883.
    143. Mohan, A., et al., Antisense oligonucleotides selectively suppress target RNA in nociceptive neurons of the pain system and can ameliorate mechanical pain. Pain, 2018. 159(1): p. 139-149.
    144. García-Tardón, N., et al., Protein kinase C (PKC)-promoted endocytosis of glutamate transporter GLT-1 requires ubiquitin ligase Nedd4-2-dependent ubiquitination but not phosphorylation. Journal of Biological Chemistry, 2012. 287(23): p. 19177-19187.
    145. Boyko, M., et al., Brain to blood glutamate scavenging as a novel therapeutic modality: a review. Journal of neural transmission, 2014. 121: p. 971-979.
    146. Niels, C.D., Glutamate uptake. Progress in Neurobiology, 2001. 65(1): p. 1-105.
    147. Rothman, S.M. and B.A. Winkelstein, Cytokine antagonism reduces pain and modulates spinal astrocytic reactivity after cervical nerve root compression. Annals of biomedical engineering, 2010. 38: p. 2563-2576.
    148. Hubbard, R.D. and B.A. Winkelstein, Transient cervical nerve root compression in the rat induces bilateral forepaw allodynia and spinal glial activation: mechanical factors in painful neck injuries. Spine, 2005. 30(17): p. 1924-1932.
    149. Nicholson, K., T. Gilliland, and B. Winkelstein, Upregulation of GLT‐1 by treatment with ceftriaxone alleviates radicular pain by reducing spinal astrocyte activation and neuronal hyperexcitability. Journal of neuroscience research, 2014. 92(1): p. 116-129.
    150. Moon, J.-Y., et al., Spinal sigma-1 receptor activation increases the production of D-serine in astrocytes which contributes to the development of mechanical allodynia in a mouse model of neuropathic pain. Pharmacological research, 2015. 100: p. 353-364.
    151. Papouin, T., et al., Synaptic and extrasynaptic NMDA receptors are gated by different endogenous coagonists. Cell, 2012. 150(3): p. 633-646.
    152. Choi, S.R., et al., Astrocyte D-serine modulates the activation of neuronal NOS leading to the development of mechanical allodynia in peripheral neuropathy. Mol Pain, 2019. 15: p. 1744806919843046.
    153. Chen, G., et al., Sex-dependent glial signaling in pathological pain: distinct roles of spinal microglia and astrocytes. Neuroscience bulletin, 2018. 34: p. 98-108.
    154. Colburn, R., A. Rickman, and J. DeLeo, The effect of site and type of nerve injury on spinal glial activation and neuropathic pain behavior. Experimental neurology, 1999. 157(2): p. 289-304.
    155. Hald, A., et al., Differential activation of spinal cord glial cells in murine models of neuropathic and cancer pain. Eur J Pain, 2009. 13(2): p. 138-45.
    156. Ono, T., et al., Mechanical pain of the lower extremity after compression of the upper spinal cord involves signal transducer and activator of transcription 3-dependent reactive astrocytes and interleukin-6. Brain, Behavior, and Immunity, 2020. 89: p. 389-399.
    157. Okada, S., et al., Astrocyte reactivity and astrogliosis after spinal cord injury. Neuroscience research, 2018. 126: p. 39-43.
    158. Miranpuri, G.S., et al., Role of microglia and astrocytes in spinal cord injury induced neuropathic pain. Annals of Neurosciences, 2021. 28(3-4): p. 219-228.
    159. Wei, X., et al., Platelet-rich plasma improves chronic inflammatory pain by inhibiting PKM2-mediated aerobic glycolysis in astrocytes. Annals of translational medicine, 2020. 8(21).
    160. Old, E.A., A.K. Clark, and M. Malcangio, The role of glia in the spinal cord in neuropathic and inflammatory pain. Pain control, 2015: p. 145-170.
    161. Sheng, H.-Y. and Y.-Q. Zhang, Emerging molecular targets for the management of cancer pain. Neuroscience Bulletin, 2020. 36(10): p. 1225-1228.
    162. Luo, H., et al., Interleukin-17 regulates neuron-glial communications, synaptic transmission, and neuropathic pain after chemotherapy. Cell reports, 2019. 29(8): p. 2384-2397. e5.
    163. Sagar, D.R., et al., The contribution of spinal glial cells to chronic pain behaviour in the monosodium iodoacetate model of osteoarthritic pain. Molecular Pain, 2011. 7: p. 1744-8069-7-88.
    164. Li, T., et al., Microglia induce the transformation of A1/A2 reactive astrocytes via the CXCR7/PI3K/Akt pathway in chronic post-surgical pain. Journal of Neuroinflammation, 2020. 17(1): p. 1-15.
    165. Cheng, T., Z. Xu, and X. Ma, The role of astrocytes in neuropathic pain. Front Mol Neurosci, 2022. 15: p. 1007889.
    166. Justicia, C., C. Gabriel, and A.M. Planas, Activation of the JAK/STAT pathway following transient focal cerebral ischemia: signaling through Jak1 and Stat3 in astrocytes. Glia, 2000. 30(3): p. 253-270.
    167. Ji, R.-R., T. Berta, and M. Nedergaard, Glia and pain: is chronic pain a gliopathy? Pain®, 2013. 154: p. S10-S28.
    168. Xu, Q., et al., Astrocytes contribute to pain gating in the spinal cord. Sci Adv, 2021. 7(45): p. eabi6287.
    169. Xie, A.X., J. Petravicz, and K.D. McCarthy, Molecular approaches for manipulating astrocytic signaling in vivo. Front Cell Neurosci, 2015. 9: p. 144.
    170. Van Den Herrewegen, Y., et al., Side-by-side comparison of the effects of Gq- and Gi-DREADD-mediated astrocyte modulation on intracellular calcium dynamics and synaptic plasticity in the hippocampal CA1. Molecular Brain, 2021. 14(1): p. 144.
    171. Iwai, Y., et al., Transient astrocytic Gq signaling underlies remote memory enhancement. Frontiers in Neural Circuits, 2021. 15: p. 658343.
    172. Tsuda, M., et al., JAK-STAT3 pathway regulates spinal astrocyte proliferation and neuropathic pain maintenance in rats. Brain, 2011. 134(4): p. 1127-1139.
    173. Bezzi, P., et al., Neuron-astrocyte cross-talk during synaptic transmission: physiological and neuropathological implications. Progress in brain research, 2001. 132: p. 255-265.
    174. Tawfik, V.L., et al., Propentofylline-induced astrocyte modulation leads to alterations in glial glutamate promoter activation following spinal nerve transection. Neuroscience, 2008. 152(4): p. 1086-1092.
    175. Tang, J., M. Bair, and G. Descalzi, Reactive Astrocytes: Critical Players in the Development of Chronic Pain. Front Psychiatry, 2021. 12: p. 682056.
    176. Bowser, D.N. and B.S. Khakh, ATP excites interneurons and astrocytes to increase synaptic inhibition in neuronal networks. Journal of Neuroscience, 2004. 24(39): p. 8606-8620.
    177. Durkee, C.A. and A. Araque, Diversity and Specificity of Astrocyte-neuron Communication. Neuroscience, 2019. 396: p. 73-78.
    178. Henneberger, C., et al., Long-term potentiation depends on release of D-serine from astrocytes. Nature, 2010. 463(7278): p. 232-236.
    179. Zhuang, Z.Y., et al., ERK is sequentially activated in neurons, microglia, and astrocytes by spinal nerve ligation and contributes to mechanical allodynia in this neuropathic pain model. Pain, 2005. 114(1-2): p. 149-59.
    180. Anderson, C.M. and R.A. Swanson, Astrocyte glutamate transport: review of properties, regulation, and physiological functions. Glia, 2000. 32(1): p. 1-14.
    181. Liaw, W.-J., et al., Spinal glutamate uptake is critical for maintaining normal sensory transmission in rat spinal cord. Pain, 2005. 115(1-2): p. 60-70.
    182. Salvatore, M.F., et al., Transient striatal GLT-1 blockade increases EAAC1 expression, glutamate reuptake, and decreases tyrosine hydroxylase phosphorylation at ser(19). Exp Neurol, 2012. 234(2): p. 428-36.
    183. Todd, A.C. and G.E. Hardingham, The Regulation of Astrocytic Glutamate Transporters in Health and Neurodegenerative Diseases. Int J Mol Sci, 2020. 21(24).
    184. Schummers, J., H. Yu, and M. Sur, Tuned responses of astrocytes and their influence on hemodynamic signals in the visual cortex. Science, 2008. 320(5883): p. 1638-1643.
    185. <Formaline DFA Effect of Inhibition of Spinal Cord Glutamate transporters.pdf>.
    186. Alotaibi, G., et al., Glial Glutamate Transporter Modulation Prevents Development of Complete Freund&rsquo;s Adjuvant-Induced Hyperalgesia and Allodynia in Mice. Brain Sciences, 2023. 13(5): p. 807.
    187. Weng, H.R., J.H. Chen, and J.P. Cata, Inhibition of glutamate uptake in the spinal cord induces hyperalgesia and increased responses of spinal dorsal horn neurons to peripheral afferent stimulation. Neuroscience, 2006. 138(4): p. 1351-60.
    188. Liaw, W.J., et al., Spinal glutamate uptake is critical for maintaining normal sensory transmission in rat spinal cord. Pain, 2005. 115(1-2): p. 60-70.
    189. Niederberger, E., et al., Modulation of spinal nociceptive processing through the glutamate transporter GLT-1. Neuroscience, 2003. 116(1): p. 81-87.
    190. Araque, A., et al., Gliotransmitters travel in time and space. Neuron, 2014. 81(4): p. 728-739.
    191. Covelo, A. and A. Araque, Neuronal activity determines distinct gliotransmitter release from a single astrocyte. elife, 2018. 7: p. e32237.
    192. Choi, S.R., et al., Spinal D-Serine Increases PKC-Dependent GluN1 Phosphorylation Contributing to the Sigma-1 Receptor-Induced Development of Mechanical Allodynia in a Mouse Model of Neuropathic Pain. J Pain, 2017. 18(4): p. 415-427.

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