High-affinity glutamate transporters in chronic pain: An emerging therapeutic target

Journal of Neurochemistry

Volumn 131, Issue 6, 2014, Pages 712-730

  Gegelashvili, Georgi ^a   Bjerrum, Ole J ^a,b  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b ILIA STATE UNIVERSITY   (Georgia)

Author keywords

amino acid transporter; excitatory amino acid transporter; gene transfer; glutamate; opioid tolerance; pain

Indexed keywords

2,4 PYRROLIDINEDICARBOXYLIC ACID; AMITRIPTYLINE; BETA LACTAM ANTIBIOTIC; CEFTRIAXONE; DIHYDROKAINIC ACID; EXCITATORY AMINO ACID TRANSPORTER; EXCITATORY AMINO ACID TRANSPORTER 3; EXCITATORY AMINO ACID TRANSPORTER 4; EXCITATORY AMINO ACID TRANSPORTER 5; GLUTAMATE RECEPTOR; GLUTAMATE TRANSPORTER; GLUTAMIC ACID; MINOCYCLINE; RILUZOLE; TETRACYCLINE; TRICYCLIC ANTIDEPRESSANT AGENT; VALPROIC ACID; VESICULAR GLUTAMATE TRANSPORTER 1; VIRUS VECTOR; ANALGESIC AGENT;

ALLODYNIA; ANALGESIC ACTIVITY; ASTROCYTE; BINDING AFFINITY; CELL MEMBRANE TRANSPORT; CHRONIC PAIN; DISEASE MODEL; DOWN REGULATION; DRUG TOLERANCE; EXCITATORY JUNCTION POTENTIAL; GENE TRANSFER; GLIA CELL; GLUTAMATERGIC TRANSMISSION; HUMAN; HYPERALGESIA; MUSCLE SPINDLE AFFERENT NERVE; NEUROMODULATION; NEUROPATHIC PAIN; NEUROPROTECTION; NEUROTRANSMISSION; NOCICEPTION; NOCICEPTIVE STIMULATION; NONHUMAN; PERIPHERAL NERVE INJURY; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PROCESSING; REVIEW; SENSORY NERVE CELL; SPINAL CORD; SPINAL GANGLION; UPREGULATION; ANIMAL; DRUG EFFECTS; METABOLISM; NERVE CELL;

AMINO ACID TRANSPORT SYSTEM X-AG; ANALGESICS; ANIMALS; CHRONIC PAIN; GLUTAMIC ACID; HUMANS; NEURONS; SPINAL CORD;

EID: 84918829132     PISSN: 00223042     EISSN: 14714159     Source Type: Journal    
DOI: 10.1111/jnc.12957     Document Type: Review

References (179)

1. Aguirre G., Rosas S., Lopez-Bayghen E., and, Ortega A., (2008) Valproate-dependent transcriptional regulation of GLAST/EAAT1 expression: involvement of Ying-Yang 1. Neurochem. Int. 52, 1322-1331.
2. Arriza J. L., Kavanaugh M. P., Fairman W. A., Wu Y. N., Murdoch G. H., North R. A., and, Amara S. G., (1993) Cloning and expression of a human neutral amino acid transporter with structural similarity to the glutamate transporter gene family. J. Biol. Chem. 268, 15329-15332.
3. Arriza J. L., Eliasof S., Kavanaugh M. P., and, Amara S. G., (1997) Excitatory amino acid transporter 5, a retinal glutamate transporter coupled to a chloride conductance. Proc. Natl Acad. Sci. USA 94, 4155-4160.
4. Azbill R. D., Mu X., and, Springer J. E., (2000) Riluzole increases high-affinity glutamate uptake in rat spinal cord synaptosomes. Brain Res. 871, 175-180.
5. Barrot M., (2012) Tests and models of nociception and pain in rodents. Neuroscience 211, 39-50.
6. Beart P. M., and, O'Shea R. D., (2007) Transporters for L-glutamate: an update on their molecular pharmacology and pathological involvement. Br. J. Pharmacol. 150, 5-17.
7. Berger U. V., and, Hediger M. A., (2000) Distribution of the glutamate transporters GLAST and GLT-1 in rat circumventricular organs, meninges, and dorsal root ganglia. J. Comp. Neurol. 421, 385-399.
8. Berger J. V., Deumens R., Goursaud S., Schafer S., Lavand'homme P., Joosten E. A., and, Hermans E., (2011) Enhanced neuroinflammation and pain hypersensitivity after peripheral nerve injury in rats expressing mutated superoxide dismutase 1. J. Neuroinflammation 8, 33.
9. Bezzi P., Gundersen V., Galbete J. L., Seifert G., Steinhauser C., Pilati E., and, Volterra A., (2004) Astrocytes contain a vesicular compartment that is competent for regulated exocytosis of glutamate. Nat. Neurosci. 7, 613-620.
10. Binns B. C., Huang Y., Goettl V. M., Hackshaw K. V., and, Stephens R. L., Jr, (2005) Glutamate uptake is attenuated in spinal deep dorsal and ventral horn in the rat spinal nerve ligation model. Brain Res. 1041, 38-47.
11. Bonde C., Sarup A., Schousboe A., Gegelashvili G., Zimmer J., and, Noraberg J., (2003) Neurotoxic and neuroprotective effects of the glutamate transporter inhibitor DL-threo-beta-benzyloxyaspartate (DL-TBOA) during physiological and ischemia-like conditions. Neurochem. Int. 43, 371-380.
12. Bunch L., Erichsen M. N., and, Jensen A. A., (2009) Excitatory amino acid transporters as potential drug targets. Expert Opin. Ther. Targets 13, 719-731.
13. Carbone M., Duty S., and, Rattray M., (2012) Riluzole elevates GLT-1 activity and levels in striatal astrocytes. Neurochem. Int. 60, 31-38.
14. Carozzi V. A., Canta A., Oggioni N., et al,. (2008) Expression and distribution of 'high affinity' glutamate transporters GLT1, GLAST, EAAC1 and of GCPII in the rat peripheral nervous system. J. Anat. 213, 539-546.
15. Cavaliere C., Cirillo G., Rosaria B. M., Rossi F., De N. V., Maione S., and, Papa M., (2007) Gliosis alters expression and uptake of spinal glial amino acid transporters in a mouse neuropathic pain model. Neuron Glia Biol. 3, 141-153.
16. Chen W., Aoki C., Mahadomrongkul V., Gruber C. E., Wang G. J., Blitzblau R., Irwin N., and, Rosenberg P. A., (2002) Expression of a variant form of the glutamate transporter GLT1 in neuronal cultures and in neurons and astrocytes in the rat brain. J. Neurosci. 22, 2142-2152.
17. Chen Z., He Y., and, Wang Z. J., (2012) The beta-lactam antibiotic, ceftriaxone, inhibits the development of opioid-induced hyperalgesia in mice. Neurosci. Lett. 509, 69-71.
18. Chen N. F., Huang S. Y., Chen W. F., Chen C. H., Lu C. H., Chen C. L., Yang S. N., Wang H. M., and, Wen Z. H., (2013) TGF-beta1 attenuates spinal neuroinflammation and the excitatory amino acid system in rats with neuropathic pain. J. Pain 14, 1671-1685.
19. Chieng B., and, Christie M. J., (2009) Chronic morphine treatment induces functional delta-opioid receptors in amygdala neurons that project to periaqueductal grey. Neuropharmacology 57, 430-437.
20. Cifra A., Mazzone G. L., and, Nistri A., (2013) Riluzole: what it does to spinal and brainstem neurons and how it does it. Neuroscientist 19, 137-144.
21. Cirillo G., Bianco M. R., Colangelo A. M., Cavaliere C., and, Daniele d. L., Zaccaro L., Alberghina L., and, Papa M., (2011) Reactive astrocytosis-induced perturbation of synaptic homeostasis is restored by nerve growth factor. Neurobiol. Dis. 41, 630-639.
22. Coderre T. J., Kumar N., Lefebvre C. D., and, Yu J. S., (2007) A comparison of the glutamate release inhibition and anti-allodynic effects of gabapentin, lamotrigine, and riluzole in a model of neuropathic pain. J. Neurochem. 100, 1289-1299.
23. Cohen S. P., and, Mao J., (2014) Neuropathic pain: mechanisms and their clinical implications. BMJ 348, f7656.
24. Conti F., DeBiasi S., Minelli A., Rothstein J. D., and, Melone M., (1998) EAAC1, a high-affinity glutamate tranporter, is localized to astrocytes and gabaergic neurons besides pyramidal cells in the rat cerebral cortex. Cereb. Cortex 8, 108-116.
25. Dall'igna O. P., Bobermin L. D., Souza D. O., and, Quincozes-Santos A., (2013) Riluzole increases glutamate uptake by cultured C6 astroglial cells. Int. J. Dev. Neurosci. 31, 482-486.
26. Danbolt N. C., (2001) Glutamate uptake. Prog. Neurobiol. 65, 1-105.
27. Darman J., Backovic S., Dike S., Maragakis N. J., Krishnan C., Rothstein J. D., Irani D. N., and, Kerr D. A., (2004) Viral-induced spinal motor neuron death is non-cell-autonomous and involves glutamate excitotoxicity. J. Neurosci. 24, 7566-7575.
28. Domercq M., and, Matute C., (1999) Expression of glutamate transporters in the adult bovine corpus callosum. Brain Res. Mol. Brain Res. 67, 296-302.
29. Dunlop J., Beal M. H., She Y., and, Howland D. S., (2003) Impaired spinal cord glutamate transport capacity and reduced sensitivity to riluzole in a transgenic superoxide dismutase mutant rat model of amyotrophic lateral sclerosis. J. Neurosci. 23, 1688-1696.
30. Eljaja L., Bjerrum O., Honore P., and, Abrahamsen B., (2011) Effects of the excitatory amino acid transporter subtype 2 (EAAT-2) inducer ceftriaxone on different pain modalities in rat. Scand. J. Pain 2, 132-136.
31. Fairman W. A., Vandenberg R. J., Arriza J. L., Kavanaugh M. P., and, Amara S. G., (1995) An excitatory amino-acid transporter with properties of a ligand-gated chloride channel. Nature 375, 599-603.
32. Figiel M., Maucher T., Rozyczka J., Bayatti N., and, Engele J., (2003) Regulation of glial glutamate transporter expression by growth factors. Exp. Neurol. 183, 124-135.
33. Fine S. M., Angel R. A., Perry S. W., Epstein L. G., Rothstein J. D., Dewhurst S., and, Gelbard H. A., (1996) Tumor necrosis factor alpha inhibits glutamate uptake by primary human astrocytes. Implications for pathogenesis of HIV-1 dementia. J. Biol. Chem. 271, 15303-15306.
34. Foran E., and, Trotti D., (2009) Glutamate transporters and the excitotoxic path to motor neuron degeneration in amyotrophic lateral sclerosis. Antioxid. Redox Signal. 11, 1587-1602.
35. Fujita K. A., Ostaszewski M., Matsuoka Y., et al,. (2014) Integrating pathways of Parkinson's disease in a molecular interaction map. Mol. Neurobiol. 49, 88-102.
36. Fumagalli E., Funicello M., Rauen T., Gobbi M., and, Mennini T., (2008) Riluzole enhances the activity of glutamate transporters GLAST, GLT1 and EAAC1. Eur. J. Pharmacol. 578, 171-176.
37. Furness D. N., Dehnes Y., Akhtar A. Q., et al,. (2008) A quantitative assessment of glutamate uptake into hippocampal synaptic terminals and astrocytes: new insights into a neuronal role for excitatory amino acid transporter 2 (EAAT2). Neuroscience 157, 80-94.
38. Gegelashvili G., and, Schousboe A., (1998) Cellular distribution and kinetic properties of high-affinity glutamate transporters. Brain Res. Bull. 45, 233-238.
39. Gegelashvili G., Civenni G., Racagni G., Danbolt N. C., Schousboe I., and, Schousboe A., (1996) Glutamate receptor agonists up-regulate glutamate transporter GLAST in astrocytes. NeuroReport 8, 261-265.
40. Gegelashvili G., Danbolt N. C., and, Schousboe A., (1997) Neuronal soluble factors differentially regulate the expression of the GLT1 and GLAST glutamate transporters in cultured astroglia. J. Neurochem. 69, 2612-2615.
41. Gegelashvili G., Dehnes Y., Danbolt N. C., and, Schousboe A., (2000) The high-affinity glutamate transporters GLT1, GLAST, and EAAT4 are regulated via different signalling mechanisms. Neurochem. Int. 37, 163-170.
42. Gegelashvili G., Robinson M. B., Trotti D., and, Rauen T., (2001) Regulation of glutamate transporters in health and disease. Prog. Brain Res. 132, 267-286.
43. Gegelashvili M., Rodriguez-Kern A., Pirozhkova I., Zhang J., Sung L., and, Gegelashvili G., (2006) High-affinity glutamate transporter GLAST/EAAT1 regulates cell surface expression of glutamine/neutral amino acid transporter ASCT2 in human fetal astrocytes. Neurochem. Int. 48, 611-615.
44. Gegelashvili M., Rodriguez-Kern A., Sung L., Shimamoto K., and, Gegelashvili G., (2007) Glutamate transporter GLAST/EAAT1 directs cell surface expression of FXYD2/gamma subunit of Na, K-ATPase in human fetal astrocytes. Neurochem. Int. 50, 916-920.
45. Genda E. N., Jackson J. G., Sheldon A. L., et al,. (2011) Co-compartmentalization of the astroglial glutamate transporter, GLT-1, with glycolytic enzymes and mitochondria. J. Neurosci. 31, 18275-18288.
46. Gosselin R. D., O'Connor R. M., Tramullas M., Julio-Pieper M., Dinan T. G., and, Cryan J. F., (2010) Riluzole normalizes early-life stress-induced visceral hypersensitivity in rats: role of spinal glutamate reuptake mechanisms. Gastroenterology 138, 2418-2425.
47. Grewer C., Gameiro A., and, Rauen T., (2014) SLC1 glutamate transporters. Pflugers Arch. 466, 3-24.
48. Gunduz O., Oltulu C., Buldum D., Guven R., and, Ulugol A., (2011) Anti-allodynic and anti-hyperalgesic effects of ceftriaxone in streptozocin-induced diabetic rats. Neurosci. Lett. 491, 23-25.
49. Guptarak J., Wanchoo S., Durham-Lee J., Wu Y., Zivadinovic D., Paulucci-Holthauzen A., and, Nesic O., (2013) Inhibition of IL-6 signaling: a novel therapeutic approach to treating spinal cord injury pain. Pain 154, 1115-1128.
50. Haugeto O., Ullensvang K., Levy L. M., Chaudhry F. A., Honore T., Nielsen M., Lehre K. P., and, Danbolt N. C., (1996) Brain glutamate transporter proteins form homomultimers. J. Biol. Chem. 271, 27715-27722.
51. Hayashida K., Parker R. A., and, Eisenach J. C., (2010) Activation of glutamate transporters in the locus coeruleus paradoxically activates descending inhibition in rats. Brain Res. 1317, 80-86.
52. Hobo S., Eisenach J. C., and, Hayashida K., (2011) Up-regulation of spinal glutamate transporters contributes to anti-hypersensitive effects of valproate in rats after peripheral nerve injury. Neurosci. Lett. 502, 52-55.
53. Holmseth S., Scott H. A., Real K., Lehre K. P., Leergaard T. B., Bjaalie J. G., and, Danbolt N. C., (2009) The concentrations and distributions of three C-terminal variants of the GLT1 (EAAT2; slc1a2) glutamate transporter protein in rat brain tissue suggest differential regulation. Neuroscience 162, 1055-1071.
54. Honore P. H., Basnet A., Kristensen P., Andersen L. M., Neustrup S., Mollgaard P., Eljaja L., and, Bjerrum O. J., (2011) Predictive validity of pharmacologic interventions in animal models of neuropathic pain. Scand. J. Pain 2, 178-184.
55. Hu W. H., Walters W. M., Xia X. M., Karmally S. A., and, Bethea J. R., (2003) Neuronal glutamate transporter EAAT4 is expressed in astrocytes. Glia 44, 13-25.
56. Hu Y., Li W., Lu L., Cai J., Xian X., Zhang M., Li Q., and, Li L., (2010) An anti-nociceptive role for ceftriaxone in chronic neuropathic pain in rats. Pain 148, 284-301.
57. Huang K. L., Shieh J. P., Chu C. C., Cheng K. I., Wang J. J., Lin M. T., and, Yeh M. Y., (2013) Prolonged analgesic effect of amitriptyline base on thermal hyperalgesia in an animal model of neuropathic pain. Eur. J. Pharmacol. 702, 20-24.
58. Jackson J. G., O'Donnell J. C., Takano H., Coulter D. A., and, Robinson M. B., (2014) Neuronal activity and glutamate uptake decrease mitochondrial mobility in astrocytes and position mitochondria near glutamate transporters. J. Neurosci. 34, 1613-1624.
59. 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 Neurosci. 26, 696-705.
60. Ji H. F., Shen L., and, Zhang H. Y., (2005) Beta-lactam antibiotics are multipotent agents to combat neurological diseases. Biochem. Biophys. Res. Commun. 333, 661-663.
61. Kabli N., and, Cahill C. M., (2007) Anti-allodynic effects of peripheral delta opioid receptors in neuropathic pain. Pain 127, 84-93.
62. Kanai Y., and, Hediger M. A., (1992) Primary structure and functional characterization of a high-affinity glutamate transporter. Nature 360, 467-471.
63. Kanai Y., Clemencon B., Simonin A., Leuenberger M., Lochner M., Weisstanner M., and, Hediger M. A., (2013) The SLC1 high-affinity glutamate and neutral amino acid transporter family. Mol. Aspects Med. 34, 108-120.
64. Klein M., Paul R., Angele B., Popp B., Pfister H. W., and, Koedel U., (2006) Protein expression pattern in experimental pneumococcal meningitis. Microbes Infect. 8, 974-983.
65. Larsson M., and, Broman J., (2011) Synaptic plasticity and pain: role of ionotropic glutamate receptors. Neuroscientist 17, 256-273.
66. Lau C. L., Perreau V. M., Chen M. J., Cate H. S., Merlo D., Cheung N. S., O'Shea R. D., and, Beart P. M., (2012) Transcriptomic profiling of astrocytes treated with the Rho kinase inhibitor fasudil reveals cytoskeletal and pro-survival responses. J. Cell. Physiol. 227, 1199-1211.
67. Lau C. L., Kovacevic M., Tingleff T. S., et al,. (2014) 3D Electrospun scaffolds promote a cytotrophic phenotype of cultured primary astrocytes. J. Neurochem. 130, 215-226.
68. Laursen J. C., Cairns B. E., Dong X. D., Kumar U., Somvanshi R. K., Arendt-Nielsen L., and, Gazerani P., (2014) Glutamate dysregulation in the trigeminal ganglion: a novel mechanism for peripheral sensitization of the craniofacial region. Neuroscience 256, 23-35.
69. Lee S. G., Su Z. Z., Emdad L., Gupta P., Sarkar D., Borjabad A., Volsky D. J., and, Fisher P. B., (2008) Mechanism of ceftriaxone induction of excitatory amino acid transporter-2 expression and glutamate uptake in primary human astrocytes. J. Biol. Chem. 283, 13116-13123.
70. Lewerenz J., Albrecht P., Tien M. L., Henke N., Karumbayaram S., Kornblum H. I., Wiedau-Pazos M., Schubert D., Maher P., and, Methner A., (2009) Induction of Nrf2 and xCT are involved in the action of the neuroprotective antibiotic ceftriaxone in vitro. J. Neurochem. 111, 332-343.
71. Liaw W. J., Stephens R. L., Jr, Binns B. C., Chu Y., Sepkuty J. P., Johns R. A., Rothstein J. D., and, Tao Y. X., (2005) Spinal glutamate uptake is critical for maintaining normal sensory transmission in rat spinal cord. Pain 115, 60-70.
72. Lim G., Wang S., and, Mao J., (2005) cAMP and protein kinase A contribute to the downregulation of spinal glutamate transporters after chronic morphine. Neurosci. Lett. 376, 9-13.
73. Lin J. A., Tsai R. Y., Lin Y. T., Lee M. S., Cherng C. H., Wong C. S., and, Tzeng J. I., (2008) Amitriptyline pretreatment preserves the antinociceptive effect of morphine in pertussis toxin-treated rats by lowering CSF excitatory amino acid concentrations and reversing the downregulation of glutamate transporters. Brain Res. 1232, 61-69.
74. Lin Y., Tian G., Roman K., Handy C., Travers J. B., Lin C. L., and, Stephens R. L., Jr, (2009) Increased glial glutamate transporter EAAT2 expression reduces visceral nociceptive response in mice. Am. J. Physiol. Gastrointest. Liver Physiol. 296, G129-G134.
75. Lin Y., Roman K., Foust K. D., Kaspar B. K., Bailey M. T., and, Stephens R. L., (2011) Glutamate transporter GLT-1 upregulation attenuates visceral nociception and hyperalgesia via spinal mechanisms not related to anti-inflammatory or probiotic effects. Pain Res. Treat. 2011, 507029.
76. Lipski J., Wan C. K., Bai J. Z., Pi R., Li D., and, Donnelly D., (2007) Neuroprotective potential of ceftriaxone in in vitro models of stroke. Neuroscience 146, 617-629.
77. Liu X. J., and, Salter M. W., (2010) Glutamate receptor phosphorylation and trafficking in pain plasticity in spinal cord dorsal horn. Eur. J. Neurosci. 32, 278-289.
78. Liu A. Y., Mathur R., Mei N., Langhammer C. G., Babiarz B., and, Firestein B. L., (2011) Neuroprotective drug riluzole amplifies the heat shock factor 1 (HSF1)- and glutamate transporter 1 (GLT1)-dependent cytoprotective mechanisms for neuronal survival. J. Biol. Chem. 286, 2785-2794.
79. Lopez-Bayghen E., and, Ortega A., (2011) Glial glutamate transporters: new actors in brain signaling. IUBMB Life 63, 816-823.
80. Maeda S., Kawamoto A., Yatani Y., Shirakawa H., Nakagawa T., and, Kaneko S., (2008) Gene transfer of GLT-1, a glial glutamate transporter, into the spinal cord by recombinant adenovirus attenuates inflammatory and neuropathic pain in rats. Mol. Pain 4, 65.
81. Maenpaa H., Gegelashvili G., and, Tahti H., (2004) Expression of glutamate transporter subtypes in cultured retinal pigment epithelial and retinoblastoma cells. Curr. Eye Res. 28, 159-165.
82. Mafra R. A., Araujo D. A., Beirao P. S., and, Cruz J. S., (2001) Glutamate transport in rat cerebellar granule cells is impaired by inorganic epileptogenic agents. Neurosci. Lett. 310, 85-88.
83. Mao Q. X., and, Yang T. D., (2010) Amitriptyline upregulates EAAT1 and EAAT2 in neuropathic pain rats. Brain Res. Bull. 81, 424-427.
84. Mao J., Sung B., Ji R. R., and, Lim G., (2002) Chronic morphine induces downregulation of spinal glutamate transporters: implications in morphine tolerance and abnormal pain sensitivity. J. Neurosci. 22, 8312-8323.
85. Mawrin C., Pap T., Pallas M., Dietzmann K., Behrens-Baumann W., and, Vorwerk C. K., (2003) Changes of retinal glutamate transporter GLT-1 mRNA levels following optic nerve damage. Mol. Vis. 9, 10-13.
86. Mei H., Xia T., Feng G., Zhu J., Lin S. M., and, Qiu Y., (2012) Opportunities in systems biology to discover mechanisms and repurpose drugs for CNS diseases. Drug Discov. Today 17, 1208-1216.
87. Melzer N., Meuth S. G., Torres-Salazar D., Bittner S., Zozulya A. L., Weidenfeller C., Kotsiari A., Stangel M., Fahlke C., and, Wiendl H., (2008) A beta-lactam antibiotic dampens excitotoxic inflammatory CNS damage in a mouse model of multiple sclerosis. PLoS ONE 3, e3149.
88. Millan M. J., (1999) The induction of pain: an integrative review. Prog. Neurobiol. 57, 1-164.
89. Miller K. E., Hoffman E. M., Sutharshan M., and, Schechter R., (2011) Glutamate pharmacology and metabolism in peripheral primary afferents: physiological and pathophysiological mechanisms. Pharmacol. Ther. 130, 283-309.
90. Mitchell R. M., Lee S. Y., Simmons Z., and, Connor J. R., (2011) HFE polymorphisms affect cellular glutamate regulation. Neurobiol. Aging 32, 1114-1123.
91. Moore R. A., Derry S., Aldington D., Cole P., and, Wiffen P. J., (2012) Amitriptyline for neuropathic pain and fibromyalgia in adults. Cochrane Database Syst. Rev. 12, CD008242.
92. Mutkus L., Aschner J. L., Fitsanakis V., and, Aschner M., (2005) The in vitro uptake of glutamate in GLAST and GLT-1 transfected mutant CHO-K1 cells is inhibited by manganese. Biol. Trace Elem. Res. 107, 221-230.
93. Nakagawa T., Ozawa T., Shige K., Yamamoto R., Minami M., and, Satoh M., (2001) Inhibition of morphine tolerance and dependence by MS-153, a glutamate transporter activator. Eur. J. Pharmacol. 419, 39-45.
94. Napier I. A., Mohammadi S. A., and, Christie M. J., (2012) Glutamate transporter dysfunction associated with nerve injury-induced pain in mice. J. Neurophysiol. 107, 649-657.
95. Nicholson K. J., Gilliland T. M., and, Winkelstein B. A., (2014a) Upregulation of GLT-1 by treatment with ceftriaxone alleviates radicular pain by reducing spinal astrocyte activation and neuronal hyperexcitability. J. Neurosci. Res. 92, 116-129.
96. Nicholson K. J., Zhang S., Gilliland T. M., and, Winkelstein B. A., (2014b) Riluzole effects on behavioral sensitivity and the development of axonal damage and spinal modifications that occur after painful nerve root compression. J. Neurosurg. Spine 20, 751-762.
97. Nie H., and, Weng H. R., (2009) Glutamate transporters prevent excessive activation of NMDA receptors and extrasynaptic glutamate spillover in the spinal dorsal horn. J. Neurophysiol. 101, 2041-2051.
98. Nie H., and, Weng H. R., (2010) Impaired glial glutamate uptake induces extrasynaptic glutamate spillover in the spinal sensory synapses of neuropathic rats. J. Neurophysiol. 103, 2570-2580.
99. Nie H., Zhang H., and, Weng H. R., (2010a) Bidirectional neuron-glia interactions triggered by deficiency of glutamate uptake at spinal sensory synapses. J. Neurophysiol. 104, 713-725.
100. Nie H., Zhang H., and, Weng H. R., (2010b) Minocycline prevents impaired glial glutamate uptake in the spinal sensory synapses of neuropathic rats. Neuroscience 170, 901-912.
101. Niederberger E., Schmidtko A., Rothstein J. D., Geisslinger G., and, Tegeder I., (2003) Modulation of spinal nociceptive processing through the glutamate transporter GLT-1. Neuroscience 116, 81-87.
102. Niederberger E., Schmidtko A., Coste O., Marian C., Ehnert C., and, Geisslinger G., (2006) The glutamate transporter GLAST is involved in spinal nociceptive processing. Biochem. Biophys. Res. Commun. 346, 393-399.
103. Nizzardo M., Nardini M., Ronchi D., et al,. (2011) Beta-lactam antibiotic offers neuroprotection in a spinal muscular atrophy model by multiple mechanisms. Exp. Neurol. 229, 214-225.
104. O'Connor A. B., (2009) Neuropathic pain: quality-of-life impact, costs and cost effectiveness of therapy. Pharmacoeconomics 27, 95-112.
105. Osikowicz M., Mika J., and, Przewlocka B., (2013) The glutamatergic system as a target for neuropathic pain relief. Exp. Physiol. 98, 372-384.
106. Peacey E., Miller C. C., Dunlop J., and, Rattray M., (2009) The four major N- and C-terminal splice variants of the excitatory amino acid transporter GLT-1 form cell surface homomeric and heteromeric assemblies. Mol. Pharmacol. 75, 1062-1073.
107. Percie du S. N., and, Rice A. S., (2014) Improving the translation of analgesic drugs to the clinic: animal models of neuropathic pain. Br. J. Pharmacol. 171, 2951-2963.
108. Perisic T., Zimmermann N., Kirmeier T., Asmus M., Tuorto F., Uhr M., Holsboer F., Rein T., and, Zschocke J., (2010) Valproate and amitriptyline exert common and divergent influences on global and gene promoter-specific chromatin modifications in rat primary astrocytes. Neuropsychopharmacology 35, 792-805.
109. Philips T., and, Rothstein J. D., (2014) Glial cells in amyotrophic lateral sclerosis. Exp. Neurol. doi: 10.1016/j.expneurol.2014.05.015. in press.
110. Piet R., Vargova L., Sykova E., Poulain D. A., and, Oliet S. H., (2004) Physiological contribution of the astrocytic environment of neurons to intersynaptic crosstalk. Proc. Natl Acad. Sci. USA 101, 2151-2155.
111. Pines G., Danbolt N. C., Bjoras M., Zhang Y., Bendahan A., Eide L., Koepsell H., Storm-Mathisen J., Seeberg E., and, Kanner B. I., (1992) Cloning and expression of a rat brain L-glutamate transporter. Nature 360, 464-467.
112. Potashner S. J., and, Tran P. L., (1984) Decreased uptake and release of D-aspartate in the guinea pig spinal cord after dorsal root section. J. Neurochem. 42, 1135-1144.
113. Potashner S. J., and, Tran P. L., (1985) Decreased uptake and release of D-aspartate in the guinea pig spinal cord after partial cordotomy. J. Neurochem. 44, 1511-1519.
114. Prow N. A., and, Irani D. N., (2008) The inflammatory cytokine, interleukin-1 beta, mediates loss of astroglial glutamate transport and drives excitotoxic motor neuron injury in the spinal cord during acute viral encephalomyelitis. J. Neurochem. 105, 1276-1286.
115. Putatunda R., Hala T. J., Chin J., and, Lepore A. C., (2014) Chronic at-level thermal hyperalgesia following rat cervical contusion spinal cord injury is accompanied by neuronal and astrocyte activation and loss of the astrocyte glutamate transporter, GLT1, in superficial dorsal horn. Brain Res. pii: S0006-8993 (14) 00651-00659. doi: 10.1016/j.brainres.2014.05.003.
116. Queen S. A., Kesslak J. P., and, Bridges R. J., (2007) Regional distribution of sodium-dependent excitatory amino acid transporters in rat spinal cord. J. Spinal Cord Med. 30, 263-271.
117. Ramos K. M., Lewis M. T., Morgan K. N., Crysdale N. Y., Kroll J. L., Taylor F. R., Harrison J. A., Sloane E. M., Maier S. F., and, Watkins L. R., (2010) Spinal upregulation of glutamate transporter GLT-1 by ceftriaxone: therapeutic efficacy in a range of experimental nervous system disorders. Neuroscience 169, 1888-1900.
118. Rattray M., and, Bendotti C., (2006) Does excitotoxic cell death of motor neurons in ALS arise from glutamate transporter and glutamate receptor abnormalities? Exp. Neurol. 201, 15-23.
119. Rauen T., Wiessner M., Sullivan R., Lee A., and, Pow D. V., (2004) A new GLT1 splice variant: cloning and immunolocalization of GLT1c in the mammalian retina and brain. Neurochem. Int. 45, 1095-1106.
120. Rawls S. M., Zielinski M., Patel H., Sacavage S., Baron D. A., and, Patel D., (2010) Beta-lactam antibiotic reduces morphine analgesic tolerance in rats through GLT-1 transporter activation. Drug Alcohol Depend. 107, 261-263.
121. Rode F., Thomsen M., Brolos T., Jensen D. G., Blackburn-Munro G., and, Bjerrum O. J., (2007) The importance of genetic background on pain behaviours and pharmacological sensitivity in the rat spared serve injury model of peripheral neuropathic pain. Eur. J. Pharmacol. 564, 103-111.
122. Rodriguez-Kern A., Gegelashvili M., Schousboe A., Zhang J., Sung L., and, Gegelashvili G., (2003) Beta-amyloid and brain-derived neurotrophic factor, BDNF, up-regulate the expression of glutamate transporter GLT-1/EAAT2 via different signaling pathways utilizing transcription factor NF-kappaB. Neurochem. Int. 43, 363-370.
123. Rojas H., Colina C., Ramos M., Benaim G., Jaffe E. H., Caputo C., and, DiPolo R., (2007) Na+ entry via glutamate transporter activates the reverse Na+/Ca2 + exchange and triggers Ca(i)2 + -induced Ca2 + release in rat cerebellar Type-1 astrocytes. J. Neurochem. 100, 1188-1202.
124. Rose E. M., Koo J. C., Antflick J. E., Ahmed S. M., Angers S., and, Hampson D. R., (2009) Glutamate transporter coupling to Na, K-ATPase. J. Neurosci. 29, 8143-8155.
125. Rothstein J. D., Martin L., Levey A. I., Dykes-Hoberg M., Jin L., Wu D., Nash N., and, Kuncl R. W., (1994) Localization of neuronal and glial glutamate transporters. Neuron 13, 713-725.
126. Rothstein J. D., Van K. M., Levey A. I., Martin L. J., and, Kuncl R. W., (1995) Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis. Ann. Neurol. 38, 73-84.
127. Rothstein J. D., Patel S., Regan M. R., et al,. (2005) Beta-lactam antibiotics offer neuroprotection by increasing glutamate transporter expression. Nature 433, 73-77.
128. Sakata H., Niizuma K., Yoshioka H., Kim G. S., Jung J. E., Katsu M., Narasimhan P., Maier C. M., Nishiyama Y., and, Chan P. H., (2012) Minocycline-preconditioned neural stem cells enhance neuroprotection after ischemic stroke in rats. J. Neurosci. 32, 3462-3473.
129. Sandkuhler J., (2009) Models and mechanisms of hyperalgesia and allodynia. Physiol. Rev. 89, 707-758.
130. Sasaki H., Sato H., Kuriyama-Matsumura K., Sato K., Maebara K., Wang H., Tamba M., Itoh K., Yamamoto M., and, Bannai S., (2002) Electrophile response element-mediated induction of the cystine/glutamate exchange transporter gene expression. J. Biol. Chem. 277, 44765-44771.
131. Schmitt A., Asan E., Lesch K. P., and, Kugler P., (2002) A splice variant of glutamate transporter GLT1/EAAT2 expressed in neurons: cloning and localization in rat nervous system. Neuroscience 109, 45-61.
132. Schneider C. H., and, de Weck A. L., (1966) Chemical aspects of penicillin allergy. The direct penicilloylation of epsilon-amino groups by penicillin at pH 7.4. Helv. Chim. Acta 49, 1695-1706.
133. Schroeder J. A., Quick K. F., Landry P. M., and, Rawls S. M., (2011) Glutamate transporter activation enhances nicotine antinociception and attenuates nicotine analgesic tolerance. NeuroReport 22, 970-973.
134. Sheean R. K., Lau C. L., Shin Y. S., O'Shea R. D., and, Beart P. M., (2013) Links between l-glutamate transporters, Na(+)/K(+)-ATPase and cytoskeleton in astrocytes: evidence following inhibition with rottlerin. Neuroscience 254, 335-346.
135. Sheldon A. L., and, Robinson M. B., (2007) The role of glutamate transporters in neurodegenerative diseases and potential opportunities for intervention. Neurochem. Int. 51, 333-355.
136. Shen C. H., Tsai R. Y., Tai Y. H., Lin S. L., Chien C. C., and, Wong C. S., (2011) Intrathecal etanercept partially restores morphine's antinociception in morphine-tolerant rats via attenuation of the glutamatergic transmission. Anesth. Analg. 113, 184-190.
137. Shen N., Mo L. Q., Hu F., Chen P. X., Guo R. X., and, Feng J. Q., (2014) A Novel Role of Spinal Astrocytic Connexin 43: mediating Morphine Antinociceptive Tolerance by Activation of NMDA Receptors and Inhibition of Glutamate Transporter-1 in Rats. CNS Neurosci. Ther. 20, 728-736.
138. Stein C., (2013) Opioids, sensory systems and chronic pain. Eur. J. Pharmacol. 716, 179-187.
139. Stepanovic-Petrovic R. M., Micov A. M., Tomic M. A., Kovacevic J. M., and, Boskovic B. D., (2013) Antihyperalgesic/Antinociceptive Effects of Ceftriaxone and Its Synergistic Interactions with Different Analgesics in Inflammatory Pain in Rodents. Anesthesiology 120, 737-750.
140. Storck T., Schulte S., Hofmann K., and, Stoffel W., (1992) Structure, expression, and functional analysis of a Na(+)-dependent glutamate/aspartate transporter from rat brain. Proc. Natl Acad. Sci. USA 89, 10955-10959.
141. Suchak S. K., Baloyianni N. V., Perkinton M. S., Williams R. J., Meldrum B. S., and, Rattray M., (2003) The 'glial' glutamate transporter, EAAT2 (Glt-1) accounts for high affinity glutamate uptake into adult rodent nerve endings. J. Neurochem. 84, 522-532.
142. Sullivan S. M., Macnab L. T., Bjorkman S. T., Colditz P. B., and, Pow D. V., (2007) GLAST1b, the exon-9 skipping form of the glutamate-aspartate transporter EAAT1 is a sensitive marker of neuronal dysfunction in the hypoxic brain. Neuroscience 149, 434-445.
143. Sung B., Lim G., and, Mao J., (2003) Altered expression and uptake activity of spinal glutamate transporters after nerve injury contribute to the pathogenesis of neuropathic pain in rats. J. Neurosci. 23, 2899-2910.
144. Sung B., Wang S., Zhou B., Lim G., Yang L., Zeng Q., Lim J. A., Wang J. D., Kang J. X., and, Mao J., (2007) Altered spinal arachidonic acid turnover after peripheral nerve injury regulates regional glutamate concentration and neuropathic pain behaviors in rats. Pain 131, 121-131.
145. Tai Y. H., Wang Y. H., Wang J. J., Tao P. L., Tung C. S., and, Wong C. S., (2006) Amitriptyline suppresses neuroinflammation and up-regulates glutamate transporters in morphine-tolerant rats. Pain 124, 77-86.
146. Tai Y. H., Wang Y. H., Tsai R. Y., Wang J. J., Tao P. L., Liu T. M., Wang Y. C., and, Wong C. S., (2007) Amitriptyline preserves morphine's antinociceptive effect by regulating the glutamate transporter GLAST and GLT-1 trafficking and excitatory amino acids concentration in morphine-tolerant rats. Pain 129, 343-354.
147. Tai Y. H., Tsai R. Y., Wang Y. H., Cherng C. H., Tao P. L., Liu T. M., and, Wong C. S., (2008) Amitriptyline induces nuclear transcription factor-kappaB-dependent glutamate transporter upregulation in chronic morphine-infused rats. Neuroscience 153, 823-831.
148. Tao F., Liaw W. J., Zhang B., Yaster M., Rothstein J. D., Johns R. A., and, Tao Y. X., (2004) Evidence of neuronal excitatory amino acid carrier 1 expression in rat dorsal root ganglion neurons and their central terminals. Neuroscience 123, 1045-1051.
149. Thone-Reineke C., Neumann C., Namsolleck P., et al,. (2008) The beta-lactam antibiotic, ceftriaxone, dramatically improves survival, increases glutamate uptake and induces neurotrophins in stroke. J. Hypertens. 26, 2426-2435.
150. Thorlin T., Roginski R. S., Choudhury K., Nilsson M., Ronnback L., Hansson E., and, Eriksson P. S., (1998) Regulation of the glial glutamate transporter GLT-1 by glutamate and delta-opioid receptor stimulation. FEBS Lett. 425, 453-459.
151. Tian G., Lai L., Guo H., Lin Y., Butchbach M. E., Chang Y., and, Lin C. L., (2007) Translational control of glial glutamate transporter EAAT2 expression. J. Biol. Chem. 282, 1727-1737.
152. Todd A. J., Hughes D. I., Polgar E., Nagy G. G., Mackie M., Ottersen O. P., and, Maxwell D. J., (2003) The expression of vesicular glutamate transporters VGLUT1 and VGLUT2 in neurochemically defined axonal populations in the rat spinal cord with emphasis on the dorsal horn. Eur. J. Neurosci. 17, 13-27.
153. Trotti D., Volterra A., Lehre K. P., Rossi D., Gjesdal O., Racagni G., and, Danbolt N. C., (1995) Arachidonic acid inhibits a purified and reconstituted glutamate transporter directly from the water phase and not via the phospholipid membrane. J. Biol. Chem. 270, 9890-9895.
154. Tzingounis A. V., and, Wadiche J. I., (2007) Glutamate transporters: confining runaway excitation by shaping synaptic transmission. Nat. Rev. Neurosci. 8, 935-947.
155. Ugbode C. I., Hirst W. D., and, Rattray M., (2014) Neuronal influences are necessary to produce mitochondrial co-localization with glutamate transporters in astrocytes. J. Neurochem. 130, 668-677.
156. Ungard R. G., Seidlitz E. P., and, Singh G., (2014) Inhibition of breast cancer-cell glutamate release with sulfasalazine limits cancer-induced bone pain. Pain 155, 28-36.
157. Utsunomiya-Tate N., Endou H., and, Kanai Y., (1996) Cloning and functional characterization of a system ASC-like Na+-dependent neutral amino acid transporter. J. Biol. Chem. 271, 14883-14890.
158. Vallejo-Illarramendi A., Domercq M., and, Matute C., (2005) A novel alternative splicing form of excitatory amino acid transporter 1 is a negative regulator of glutamate uptake. J. Neurochem. 95, 341-348.
159. Vandenberg R. J., and, Ryan R. M., (2013) Mechanisms of glutamate transport. Physiol. Rev. 93, 1621-1657.
160. Vanderah T. W., (2010) Delta and kappa opioid receptors as suitable drug targets for pain. Clin. J. Pain 26 (Suppl 10), S10-S15.
161. Vera-Portocarrero L. P., Mills C. D., Ye Z., Fullwood S. D., McAdoo D. J., Hulsebosch C. E., and, Westlund K. N., (2002) Rapid changes in expression of glutamate transporters after spinal cord injury. Brain Res. 927, 104-110.
162. Wang Z., Pekarskaya O., Bencheikh M., Chao W., Gelbard H. A., Ghorpade A., Rothstein J. D., and, Volsky D. J., (2003) Reduced expression of glutamate transporter EAAT2 and impaired glutamate transport in human primary astrocytes exposed to HIV-1 or gp120. Virology 312, 60-73.
163. Wen Z. H., Wu G. J., Chang Y. C., Wang J. J., and, Wong C. S., (2005) Dexamethasone modulates the development of morphine tolerance and expression of glutamate transporters in rats. Neuroscience 133, 807-817.
164. Weng H. R., Chen J. H., and, Cata J. P., (2006) Inhibition of glutamate uptake in the spinal cord induces hyperalgesia and increased responses of spinal dorsal horn neurons to peripheral afferent stimulation. Neuroscience 138, 1351-1360.
165. Weng H. R., Gao M., and, Maixner D. W., (2014) Glycogen synthase kinase 3 beta regulates glial glutamate transporter protein expression in the spinal dorsal horn in rats with neuropathic pain. Exp. Neurol. 252, 18-27.
166. Woolf C. J., (2011) Central sensitization: implications for the diagnosis and treatment of pain. Pain 152, S2-S15.
167. Xia P., Pei G., and, Schwarz W., (2006) Regulation of the glutamate transporter EAAC1 by expression and activation of delta-opioid receptor. Eur. J. Neurosci. 24, 87-93.
168. Xin W. J., Weng H. R., and, Dougherty P. M., (2009) Plasticity in expression of the glutamate transporters GLT-1 and GLAST in spinal dorsal horn glial cells following partial sciatic nerve ligation. Mol. Pain 5, 15.
169. Yamada K., Watanabe M., Shibata T., Nagashima M., Tanaka K., and, Inoue Y., (1998) Glutamate transporter GLT-1 is transiently localized on growing axons of the mouse spinal cord before establishing astrocytic expression. J. Neurosci. 18, 5706-5713.
170. Yan H., Li C. M., Li Y. L., and, Gong Z. H., (2009) Effect of spinal glutamate transporter 1 on chronic constriction injury of sciatic nerve and morphine tolerance of rats. Yao Xue. Xue. Bao. 44, 581-585.
171. Yan X., Yadav R., Gao M., and, Weng H. R., (2014) Interleukin-1 beta enhances endocytosis of glial glutamate transporters in the spinal dorsal horn through activating protein kinase C. Glia 62, 1093-1109.
172. Yang L., Wang S., Lim G., Sung B., Zeng Q., and, Mao J., (2008a) Inhibition of the ubiquitin-proteasome activity prevents glutamate transporter degradation and morphine tolerance. Pain 140, 472-478.
173. Yang L., Wang S., Sung B., Lim G., and, Mao J., (2008b) Morphine induces ubiquitin-proteasome activity and glutamate transporter degradation. J. Biol. Chem. 283, 21703-21713.
174. Yang M., Roman K., Chen D. F., Wang Z. G., Lin Y., and, Stephens R. L., Jr, (2011) GLT-1 overexpression attenuates bladder nociception and local/cross-organ sensitization of bladder nociception. Am. J. Physiol. Renal Physiol. 300, F1353-F1359.
175. Yaster M., Guan X., Petralia R. S., Rothstein J. D., Lu W., and, Tao Y. X., (2011) Effect of inhibition of spinal cord glutamate transporters on inflammatory pain induced by formalin and complete Freund's adjuvant. Anesthesiology 114, 412-423.
176. Yogeeswari P., Semwal A., Mishra R., and, Sriram D., (2009) Current approaches with the glutamatergic system as targets in the treatment of neuropathic pain. Expert Opin. Ther. Targets 13, 925-943.
177. Yoshizumi M., Eisenach J. C., and, Hayashida K., (2012) Riluzole and gabapentinoids activate glutamate transporters to facilitate glutamate-induced glutamate release from cultured astrocytes. Eur. J. Pharmacol. 677, 87-92.
178. Zerangue N., Arriza J. L., Amara S. G., and, Kavanaugh M. P., (1995) Differential modulation of human glutamate transporter subtypes by arachidonic acid. J. Biol. Chem. 270, 6433-6435.
179. Zhou Y., and, Danbolt N. C., (2014) Glutamate as a neurotransmitter in the healthy brain. J. Neural. Transm. 121, 799-817.