Targeting N-methyl-D-aspartate receptors for treatment of neuropathic pain

Expert Review of Clinical Pharmacology

Volumn 4, Issue 3, 2011, Pages 379-388

  Zhou, Hong Yi ^a   Chen, Shao Rui ^a   Pan, Hui Lin ^a,b  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^b UNIVERSITY OF TEXAS   (United States)

Author keywords

complex regional pain syndrome; diabetic neuropathy; neuropathic pain; NMDA receptors; spinal cord; synaptic plasticity; synaptic transmission

Indexed keywords

2 AMINO 5 PHOSPHONOVALERIC ACID; 4,6 DICHLORO 3 (2 OXO 1 PHENYL 3 PYRROLIDINYLIDENEMETHYL) 1H INDOLE 2 CARBOXYLIC ACID; 5,7 DICHLOROKINURENIC ACID; 7 CHLORO 4 HYDROXY 3 (3 PHENOXYPHENYL) 2 QUINOLONE; AMANTADINE; CALCIUM CALMODULIN DEPENDENT PROTEIN KINASE II; DEXTROMETHORPHAN; DEXTRORPHAN; DIZOCILPINE; DRUG METABOLITE; IFENPRODIL; KETAMINE; MEMANTINE; MRZ 2576; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; N METHYL DEXTRO ASPARTIC ACID RECEPTOR 1; N METHYL DEXTRO ASPARTIC ACID RECEPTOR 2A; N METHYL DEXTRO ASPARTIC ACID RECEPTOR 2B; N METHYL DEXTRO ASPARTIC ACID RECEPTOR 2C; N METHYL DEXTRO ASPARTIC ACID RECEPTOR 2D; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; NERAMEXANE; NORKETAMINE; PLACEBO; PYRIDAZINOQUINOLINETRIONE DERIVATIVE; RADIPRODIL; RO 256981; TRAXOPRODIL; UNCLASSIFIED DRUG; UNINDEXED DRUG; ZENVIA;

ALLODYNIA; ANALGESIC ACTIVITY; CENTRAL NERVOUS SYSTEM DISEASE; CHRONIC LIMB PAIN; CHRONIC PAIN; CLINICAL TRIAL (TOPIC); COMPLEX REGIONAL PAIN SYNDROME; DIABETIC NEUROPATHY; DISSOCIATIVE DISORDER; DROWSINESS; DRUG EFFICACY; DRUG TARGETING; HALLUCINATION; HUMAN; HYPERALGESIA; LIMB PAIN; LOW DRUG DOSE; MEMORY DISORDER; MOTOR DYSFUNCTION; NERVE INJURY; NEUROPATHIC PAIN; NEUROTRANSMISSION; NOCICEPTION; NONHUMAN; POSTHERPETIC NEURALGIA; POSTOPERATIVE PAIN; PROTEIN PHOSPHORYLATION; PROTEIN STRUCTURE; REGULATORY MECHANISM; RESTLESSNESS; REVIEW; SCIATIC NEUROPATHY; SENSORY NEUROPATHY; SPINAL CORD INJURY; UNSPECIFIED SIDE EFFECT; VIVID DREAM;

ANALGESICS; ANIMALS; DRUG DELIVERY SYSTEMS; EXCITATORY AMINO ACID ANTAGONISTS; HUMANS; NEURALGIA; RECEPTORS, N-METHYL-D-ASPARTATE;

EID: 79955979808     PISSN: 17512433     EISSN: 17512441     Source Type: Journal    
DOI: 10.1586/ecp.11.17     Document Type: Review

References (130)

1. American Pain Foundation. Overview of American pain surveys: 2005-2006. J. Pain Palliat. Care Pharmacother. 22, 33-38 (2008).
2. Hollmann M, Boulter J, Maron C et al. Zinc potentiates agonist-induced currents at certain splice variants of the NMDA receptor. Neuron 10, 943-954 (1993). (Pubitemid 23152049)
3. Kutsuwada T, Kashiwabuchi N, Mori H et al. Molecular diversity of the NMDA receptor channel. Nature 358, 36-41 (1992).
4. Monyer H, Sprengel R, Schoepfer R et al. Heteromeric NMDA receptors: molecular and functional distinction of subtypes. Science 256, 1217-1221 (1992).
5. Ciabarra AM, Sullivan JM, Gahn LG et al. Cloning and characterization of chi-1: a developmentally regulated member of a novel class of the ionotropic glutamate receptor family. J. Neurosci. 15, 6498-6508 (1995). (Pubitemid 3001297)
6. Sun L, Margolis FL, Shipley MT, Lidow MS. Identification of a long variant of mRNA encoding the NR3 subunit of the NMDA receptor: its regional distribution and developmental expression in the rat brain. FEBS Lett. 441, 392-396 (1998). (Pubitemid 29065322)
7. Nishi M, Hinds H, Lu HP, Kawata M, Hayashi Y. Motoneuron-specific expression of NR3B, a novel NMDA-type glutamate receptor subunit that works in a dominant-negative manner. J. Neurosci. 21, RC185 (2001).
8. Chatterton JE, Awobuluyi M, Premkumar LS et al. Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits. Nature 415, 793-798 (2002). (Pubitemid 34150501)
9. Vicini S, Wang JF, Li JH et al. Functional and pharmacological differences between recombinant N-methyl-D-aspartate receptors. J. Neurophysiol. 79, 555-566 (1998). (Pubitemid 28095877)
10. Monyer H, Burnashev N, Laurie DJ, Sakmann B, Seeburg PH. Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron 12, 529-540 (1994). (Pubitemid 24100885)
11. Sheng M, Cummings J, Roldan LA, Jan YN, Jan LY. Changing subunit composition of heteromeric NMDA receptors during development of rat cortex. Nature 368, 144-147 (1994). (Pubitemid 24101524)
12. Laurie DJ, Bartke I, Schoepfer R, Naujoks K, Seeburg PH. Regional, developmental and interspecies expression of the four NMDAR2 subunits, examined using monoclonal antibodies. Brain Res. Mol. Brain Res. 51, 23-32 (1997). (Pubitemid 27504028)
13. Stocca G, Vicini S. Increased contribution of NR2A subunit to synaptic NMDA receptors in developing rat cortical neurons. J. Physiol. 507, 13-24 (1998). (Pubitemid 28102672)
14. Tovar KR, Westbrook GL. The incorporation of NMDA receptors with a distinct subunit composition at nascent hippocampal synapses in vitro. J. Neurosci. 19, 4180-4188 (1999). (Pubitemid 29222289)
15. Townsend M, Yoshii A, Mishina M, Constantine-Paton M. Developmental loss of miniature N-methyl-D-aspartate receptor currents in NR2A knockout mice. Proc. Natl Acad. Sci. USA 100, 1340-1345 (2003). (Pubitemid 36184003)
16. Momiyama A. Distinct synaptic and extrasynaptic NMDA receptors identified in dorsal horn neurones of the adult rat spinal cord. J. Physiol. 523, 621-628 (2000). (Pubitemid 30153822)
17. Thompson CL, Drewery DL, Atkins HD, Stephenson FA, Chazot PL. Immunohistochemical localization of N-methyl-D-aspartate receptor subunits in the adult murine hippocampal formation: evidence for a unique role of the NR2D subunit. Brain Res. Mol. Brain Res. 102, 55-61 (2002). (Pubitemid 34607742)
18. Yung KK. Localization of glutamate receptors in dorsal horn of rat spinal cord. Neuroreport 9, 1639-1644 (1998). (Pubitemid 28264301)
19. Boyce S, Wyatt A, Webb JK et al. Selective NMDA NR2B antagonists induce antinociception without motor dysfunction: correlation with restricted localisation of NR2B subunit in dorsal horn. Neuropharmacology 38, 611-623 (1999). (Pubitemid 29150316)
20. Nagy GG, Watanabe M, Fukaya M, Todd AJ. Synaptic distribution of the NR1, NR2A and NR2B subunits of the N-methyl-D-aspartate receptor in the rat lumbar spinal cord revealed with an antigen-unmasking technique. Eur. J. Neurosci. 20, 3301-3312 (2004). (Pubitemid 40013539)
21. Sato K, Kiyama H, Park HT, Tohyama M. AMPA, KA and NMDA receptors are expressed in the rat DRG neurones. Neuroreport 4, 1263-1265 (1993). (Pubitemid 23289208)
22. Liu H, Wang H, Sheng M et al. Evidence for presynaptic N-methyl-D-aspartate autoreceptors in the spinal cord dorsal horn. Proc. Natl Acad. Sci. USA 91, 8383-8387 (1994).
23. Marvizon JC, McRoberts JA, Ennes HS et al. Two N-methyl-D-aspartate receptors in rat dorsal root ganglia with different subunit composition and localization. J. Comp. Neurol. 446, 325-341 (2002). (Pubitemid 34303731)
24. Li J, McRoberts JA, Nie J, Ennes HS, Mayer EA. Electrophysiological characterization of N-methyl-D-aspartate receptors in rat dorsal root ganglia neurons. Pain 109, 443-452 (2004). (Pubitemid 38638721)
25. Matsuda K, Kamiya Y, Matsuda S, Yuzaki M. Cloning and characterization of a novel NMDA receptor subunit NR3B: a dominant subunit that reduces calcium permeability. Brain Res. Mol. Brain Res. 100, 43-52 (2002). (Pubitemid 34465577)
26. Perez-Otano I, Schulteis CT, Contractor A et al. Assembly with the NR1 subunit is required for surface expression of NR3A-containing NMDA receptors. J. Neurosci. 21, 1228-1237 (2001). (Pubitemid 32128767)
27. Matsuda K, Fletcher M, Kamiya Y, Yuzaki M. Specific assembly with the NMDA receptor 3B subunit controls surface expression and calcium permeability of NMDA receptors. J. Neurosci. 23, 10064-10073 (2003). (Pubitemid 37392553)
28. Wong HK, Liu XB, Matos MF et al. Temporal and regional expression of NMDA receptor subunit NR3A in the mammalian brain. J. Comp. Neurol. 450, 303-317 (2002). (Pubitemid 34809383)
29. Prithviraj R, Inglis FM. Expression of the N-methyl-D-aspartate receptor subunit NR3B regulates dendrite morphogenesis in spinal motor neurons. Neuroscience 155, 145-153 (2008).
30. Wee KS, Zhang Y, Khanna S, Low CM. Immunolocalization of NMDA receptor subunit NR3B in selected structures in the rat forebrain, cerebellum, and lumbar spinal cord. J. Comp. Neurol. 509, 118-135 (2008). (Pubitemid 351846404)
31. 2+ of NMDA responses in spinal cord neurones. Nature 309, 261-263 (1984). (Pubitemid 14139936)
32. Nowak L, Bregestovski P, Ascher P, Herbet A, Prochiantz A. Magnesium gates glutamate-activated channels in mouse central neurones. Nature 307, 462-465 (1984). (Pubitemid 14132062)
33. Burzomato V, Frugier G, Perez-Otano I, Kittler JT, Attwell D. The receptor subunits generating NMDA receptor mediated currents in oligodendrocytes. J. Physiol. 588, 3403-3414 (2010).
34. 2+. J. Physiol. 506, 13-32 (1998). (Pubitemid 28046035)
35. Bardoni R, Magherini PC, MacDermott AB. NMDA EPSCs at glutamatergic synapses in the spinal cord dorsal horn of the postnatal rat. J. Neurosci. 18, 6558-6567 (1998). (Pubitemid 28373257)
36. Zhou HY, Zhang HM, Chen SR, Pan HL. Increased C-fiber nociceptive input potentiates inhibitory glycinergic transmission in the spinal dorsal horn. J. Pharmacol. Exp. Ther. 324, 1000-1010 (2008).
37. Raman IM, Tong G, Jahr CE. βadrenergic regulation of synaptic NMDA receptors by cAMP-dependent protein kinase. Neuron 16, 415-421 (1996).
38. Tingley WG, Ehlers MD, Kameyama K et al. Characterization of protein kinase A and protein kinase C phosphorylation of the N-methyl-D-aspartate receptor NR1 subunit using phosphorylation site-specific antibodies. J. Biol. Chem. 272, 5157-5166 (1997). (Pubitemid 27090073)
39. Leonard AS, Hell JW. Cyclic AMP-dependent protein kinase and protein kinase C phosphorylate N-methyl-D-aspartate receptors at different sites. J. Biol. Chem. 272, 12107-12115 (1997). (Pubitemid 27202791)
40. 2+ block of NMDA-receptor channels as a mechanism of modulation. Nature 356, 521-523 (1992).
41. Lieberman DN, Mody I. Casein kinase-II regulates NMDA channel function in hippocampal neurons. Nat. Neurosci. 2, 125-132 (1999). (Pubitemid 30491311)
42. Chung HJ, Huang YH, Lau LF, Huganir RL. Regulation of the NMDA receptor complex and trafficking by activity-dependent phosphorylation of the NR2B subunit PDZ ligand. J. Neurosci. 24, 10248-10259 (2004). (Pubitemid 39492052)
43. Leonard AS, Lim IA, Hemsworth DE, Horne MC, Hell JW. Calcium/calmodulin- dependent protein kinase II is associated with the N-methyl-D-aspartate receptor. Proc. Natl Acad. Sci. USA 96, 3239-3244 (1999). (Pubitemid 29148875)
44. Barria A, Malinow R. NMDA receptor subunit composition controls synaptic plasticity by regulating binding to CaMKII. Neuron 48, 289-301 (2005). (Pubitemid 41476362)
45. Yu XM, Askalan R, Keil GJ 2nd, Salter MW. NMDA channel regulation by channel-associated protein tyrosine kinase Src. Science 275, 674-678 (1997). (Pubitemid 27061336)
46. Kohr G, Seeburg PH. Subtype-specific regulation of recombinant NMDA receptor-channels by protein tyrosine kinases of the Src family. J. Physiol. 492, 445-452 (1996). (Pubitemid 26137754)
47. Wechsler A , Teichberg VI. Brain spectrin binding to the NMDA receptor is regulated by phosphorylation, calcium and calmodulin. EMBO J. 17, 3931-3939 (1998). (Pubitemid 28333979)
48. Abe T, Matsumura S, Katano T et al. Fyn kinase-mediated phosphorylation of NMDA receptor NR2B subunit at Tyr1472 is essential for maintenance of neuropathic pain. Eur. J. Neurosci. 22, 1445-1454 (2005). (Pubitemid 41442416)
49. Lu WY, Xiong ZG, Lei S et al. G-protein-coupled receptors act via protein kinase C and Src to regulate NMDA receptors. Nat. Neurosci. 2, 331-338 (1999). (Pubitemid 30491275)
50. Markram H, Segal M. Activation of protein kinase C suppresses responses to NMDA in rat CA1 hippocampal neurones. J. Physiol. 457, 491-501 (1992).
51. Raymond LA, Tingley WG, Blackstone CD, Roche KW, Huganir RL. Glutamate receptor modulation by protein phosphorylation. J. Physiol. (Paris) 88, 181-192 (1994). (Pubitemid 24307056)
52. Huang Y, Lu W, Ali DW et al. CAKβ/Pyk2 kinase is a signaling link for induction of long-term potentiation in CA1 hippocampus. Neuron 29, 485-496 (2001). (Pubitemid 32206485)
53. Jones ML, Leonard JP. PKC site mutations reveal differential modulation by insulin of NMDA receptors containing NR2A or NR2B subunits. J. Neurochem. 92, 1431-1438 (2005). (Pubitemid 40389212)
54. Liao GY, Wagner DA, Hsu MH, Leonard JP. Evidence for direct protein kinase-C mediated modulation of N-methyl-D-aspartate receptor current. Mol. Pharmacol. 59, 960-964 (2001). (Pubitemid 32381573)
55. Crump FT, Dillman KS, Craig AM. cAMP-dependent protein kinase mediates activity-regulated synaptic targeting of NMDA receptors. J. Neurosci. 21, 5079-5088 (2001). (Pubitemid 32622933)
56. Omkumar RV, Kiely MJ, Rosenstein AJ, Min KT, Kennedy MB. Identification of a phosphorylation site for calcium/ calmodulin dependent protein kinase II in the NR2B subunit of the N-methyl-D-aspartate receptor. J. Biol. Chem. 271, 31670-31678 (1996). (Pubitemid 26408631)
57. Wang YT, Salter MW. Regulation of NMDA receptors by tyrosine kinases and phosphatases. Nature 369, 233-235 (1994). (Pubitemid 24154800)
58. Lu YM, Roder JC, Davidow J, Salter MW. Src activation in the induction of long-term potentiation in CA1 hippocampal neurons. Science 279, 1363-1367 (1998). (Pubitemid 28119580)
59. Zheng F, Gingrich MB, Traynelis SF, Conn PJ. Tyrosine kinase potentiates NMDA receptor currents by reducing tonic zinc inhibition. Nat. Neurosci. 1, 185-191 (1998).
60. Lau LF and Huganir RL. Differential tyrosine phosphorylation of N-methyl-D-aspartate receptor subunits. J. Biol. Chem. 270, 20036-20041 (1995).
61. Yang M, Leonard JP. Identification of mouse NMDA receptor subunit NR2A C-terminal tyrosine sites phosphorylated by coexpression with v-Src. J. Neurochem. 77, 580-588 (2001). (Pubitemid 32298752)
62. Moon IS, Apperson ML, Kennedy MB. The major tyrosine-phosphorylated protein in the postsynaptic density fraction is N-methyl-D-aspartate receptor subunit 2B. Proc. Natl Acad. Sci. USA 91, 3954-3958 (1994). (Pubitemid 24139551)
63. Rostas JA, Brent VA, Voss K et al. Enhanced tyrosine phosphorylation of the 2B subunit of the N-methyl-D-aspartate receptor in long-term potentiation. Proc. Natl Acad. Sci. USA 93, 10452-10456 (1996).
64. Lin SY, Wu K, Levine ES et al. BDNF acutely increases tyrosine phosphorylation of the NMDA receptor subunit 2B in cortical and hippocampal postsynaptic densities. Brain Res. Mol. Brain Res. 55, 20-27 (1998). (Pubitemid 28236587)
65. Nakazawa T, Komai S, Tezuka T et al. Characterization of Fyn-mediated tyrosine phosphorylation sites on GluR ε 2 (NR2B) subunit of the N-methyl-D-aspartate receptor. J. Biol. Chem. 276, 693-699 (2001). (Pubitemid 32050862)
66. Chen C, Leonard JP. Protein tyrosine kinase-mediated potentiation of currents from cloned NMDA receptors. J. Neurochem. 67, 194-200 (1996). (Pubitemid 26185597)
67. Charriaut-Marlangue C, Otani S, Creuzet C, Ben-Ari Y, Loeb J. Rapid activation of hippocampal casein kinase II during long-term potentiation. Proc. Natl Acad. Sci. USA 88, 10232-10236 (1991). (Pubitemid 21915809)
68. Kimura R, Matsuki N. Protein kinase CK2 modulates synaptic plasticity by modification of synaptic NMDA receptors in the hippocampus. J. Physiol. 586, 3195-3206 (2008). (Pubitemid 351984699)
69. Soto D, Pancetti F, Marengo JJ et al. Protein kinase CK2 in postsynaptic densities: phosphorylation of PSD-95/ SAP90 and NMDA receptor regulation. Biochem. Biophys. Res. Commun. 322, 542-550 (2004). (Pubitemid 39490338)
70. Sanz-Clemente A, Matta JA, Isaac JT, Roche KW. Casein kinase 2 regulates the NR2 subunit composition of synaptic NMDA receptors. Neuron 67, 984-996 (2010).
71. Wang LY, Orser BA, Brautigan DL, MacDonald JF. Regulation of NMDA receptors in cultured hippocampal neurons by protein phosphatases 1 and 2A. Nature 369, 230-232 (1994). (Pubitemid 24154799)
72. 2+-dependent phosphatase. Nature 369, 235-239 (1994). (Pubitemid 24154801)
73. 2+-independent reduction of N-methyl-D-aspartate channel activity by protein tyrosine phosphatase. Proc. Natl Acad. Sci. USA 93, 1721-1725 (1996).
74. Zhang HM, Chen SR, Pan HL. Effects of activation of group III metabotropic glutamate receptors on spinal synaptic transmission in a rat model of neuropathic pain. Neuroscience 158, 875-884 (2009).
75. Li JQ, Chen SR, Chen H, Cai YQ, Pan HL. Regulation of increased glutamatergic input to spinal dorsal horn neurons by mGluR5 in diabetic neuropathic pain. J. Neurochem. 112, 162-172 (2010).
76. Wang XL, Zhang HM, Chen SR, Pan HL. Altered synaptic input and GABAB receptor function in spinal superficial dorsal horn neurons in rats with diabetic neuropathy. J. Physiol. 579, 849-861 (2007).
77. Zhou HY, Chen SR, Chen H, Pan HL. Functional plasticity of group II metabotropic glutamate receptors in regulating spinal excitatory and inhibitory synaptic input in neuropathic pain. J. Pharmacol. Exp. Ther. 336, 254-264 (2011).
78. Liu H, Mantyh PW, Basbaum AI. NMDA-receptor regulation of substance P release from primary afferent nociceptors. Nature 386, 721-724 (1997). (Pubitemid 27193493)
79. Zhou HY, Chen SR, Chen H, Pan HL. Opioid-induced long-term potentiation in the spinal cord is a presynaptic event. J. Neurosci. 30, 4460-4466 (2010).
80. Bardoni R, Torsney C, Tong CK, Prandini M, MacDermott AB. Presynaptic NMDA receptors modulate glutamate release from primary sensory neurons in rat spinal cord dorsal horn. J. Neurosci. 24, 2774-2781 (2004). (Pubitemid 38380954)
81. Wu ZZ, Chen SR, Pan HL. Transient receptor potential vanilloid type 1 activation down-regulates voltage-gated calcium channels through calcium-dependent calcineurin in sensory neurons. J. Biol. Chem. 280, 18142-18151 (2005).
82. 2+ transients in the rat substantia gelatinosa neurons after ligation of L5-L6 spinal nerves. Neuroreport 11, 4055-4061 (2000). (Pubitemid 32038803)
83. Zhou HY, Zhang HM, Chen SR, Pan HL. Protein kinase CK2 increases synaptic NMDA receptor activity in the spinal cord in neuropathic pain. Neurosci. Abstr. 39, 613.3/B88 (2009).
84. Ultenius C, Linderoth B, Meyerson BA, Wallin J. Spinal NMDA receptor phosphorylation correlates with the presence of neuropathic signs following peripheral nerve injury in the rat. Neurosci. Lett. 399, 85-90 (2006).
85. Gao X, Kim HK, Chung JM, Chung K. Enhancement of NMDA receptor phosphorylation of the spinal dorsal horn and nucleus gracilis neurons in neuropathic rats. Pain 116, 62-72 (2005). (Pubitemid 40828501)
86. Liu XJ, Gingrich JR, Vargas-Caballero M et al. Treatment of inflammatory and neuropathic pain by uncoupling Src from the NMDA receptor complex. Nat. Med. 14, 1325-1332 (2008).
87. Herrero JF, Laird JM, Lopez-Garcia JA. Wind-up of spinal cord neurones and pain sensation: much ado about something? Prog. Neurobiol. 61, 169-203 (2000). (Pubitemid 30110477)
88. Davies SN and Lodge D. Evidence for involvement of N-methylaspartate receptors in 'wind-up' of class 2 neurones in the dorsal horn of the rat. Brain Res. 424, 402-406 (1987). (Pubitemid 18047687)
89. Dickenson AH and Sullivan AF. Evidence for a role of the NMDA receptor in the frequency dependent potentiation of deep rat dorsal horn nociceptive neurones following C fibre stimulation. Neuropharmacology 26, 1235-1238 (1987). (Pubitemid 17123438)
90. Suzuki R, Matthews EA, Dickenson AH. Comparison of the effects of MK-801, ketamine and memantine on responses of spinal dorsal horn neurones in a rat model of mononeuropathy. Pain 91, 101-109 (2001). (Pubitemid 32274179)
91. Iwata H, Takasusuki T, Yamaguchi S, Hori Y. NMDA receptor 2B subunit-mediated synaptic transmission in the superficial dorsal horn of peripheral nerve-injured neuropathic mice. Brain Res. 1135, 92-101 (2007). (Pubitemid 46176831)
92. Qu XX, Cai J, Li MJ et al. Role of the spinal cord NR2βcontaining NMDA receptors in the development of neuropathic pain. Exp. Neurol. 215, 298-307 (2009).
93. Miletic G, Pankratz MT, Miletic V. Increases in the phosphorylation of cyclic AMP response element binding protein (CREB) and decreases in the content of calcineurin accompany thermal hyperalgesia following chronic constriction injury in rats. Pain 99, 493-500 (2002). (Pubitemid 35284281)
94. Mao J, Price DD, Hayes RL et al. Intrathecal treatment with dextrorphan or ketamine potently reduces pain-related behaviors in a rat model of peripheral mononeuropathy. Brain Res. 605, 164-168 (1993). (Pubitemid 23083073)
95. Eisenberg E, LaCross S, Strassman AM. The clinically tested N-methyl-D-aspartate receptor antagonist memantine blocks and reverses thermal hyperalgesia in a rat model of painful mononeuropathy. Neurosci. Lett. 187, 17-20 (1995).
96. Mao J, Price DD, Mayer DJ, Lu J, Hayes RL. Intrathecal MK-801 and local nerve anesthesia synergistically reduce nociceptive behaviors in rats with experimental peripheral mononeuropathy. Brain Res. 576, 254-262 (1992).
97. Davar G, Hama A, Deykin A, Vos B, Maciewicz R. MK-801 blocks the development of thermal hyperalgesia in a rat model of experimental painful neuropathy. Brain Res. 553, 327-330 (1991).
98. Qian J, Brown SD, Carlton SM. Systemic ketamine attenuates nociceptive behaviors in a rat model of peripheral neuropathy. Brain Res. 715, 51-62 (1996). (Pubitemid 26141651)
99. Chaplan SR, Malmberg AB, Yaksh TL. Efficacy of spinal NMDA receptor antagonism in formalin hyperalgesia and nerve injury evoked allodynia in the rat. J. Pharmacol. Exp. Ther. 280, 829-838 (1997). (Pubitemid 27171346)
100. Bennett AD, Everhart AW, Hulsebosch CE. Intrathecal administration of an NMDA or a non-NMDA receptor antagonist reduces mechanical but not thermal allodynia in a rodent model of chronic central pain after spinal cord injury. Brain Res. 859, 72-82 (2000). (Pubitemid 30138194)
101. Holtman JR Jr, Crooks PA, Johnson-Hardy JK et al. Effects of norketamine enantiomers in rodent models of persistent pain. Pharmacol. Biochem. Behav. 90, 676-685 (2008).
102. Chen SR, Samoriski G, Pan HL. Antinociceptive effects of chronic administration of uncompetitive NMDA receptor antagonists in a rat model of diabetic neuropathic pain. Neuropharmacology 57, 121-126 (2009).
103. Christoph T, Reissmuller E, Schiene K, Englberger W, Chizh BA. Antiallodynic effects of NMDA glycine(B) antagonists in neuropathic pain: possible peripheral mechanisms. Brain Res. 1048, 218-227 (2005). (Pubitemid 40803505)
104. Christoph T, Schiene K, Englberger W, Parsons CG, Chizh BA. The antiallodynic effect of NMDA antagonists in neuropathic pain outlasts the duration of the in vivo NMDA antagonism. Neuropharmacology 51, 12-17 (2006). (Pubitemid 44192397)
105. Quartaroli M, Carignani C, Dal Forno G et al. Potent antihyperalgesic activity without tolerance produced by glycine site antagonist of N-methyl-D-aspartate receptor GV196771A. J. Pharmacol. Exp. Ther. 290, 158-169 (1999). (Pubitemid 29302316)
106. Quartaroli M, Fasdelli N, Bettelini L, Maraia G, Corsi M. GV196771A, an NMDA receptor/glycine site antagonist, attenuates mechanical allodynia in neuropathic rats and reduces tolerance induced by morphine in mice. Eur. J. Pharmacol. 430, 219-227 (2001). (Pubitemid 33050041)
107. Bare TM, Brown DG, Horchler CL et al. Pyridazinoquinolinetriones as NMDA glycine-site antagonists with oral antinociceptive activity in a model of neuropathic pain. J. Med. Chem. 50, 3113-3131 (2007). (Pubitemid 47001253)
108. Zhang W, Shi CX, Gu XP, Ma ZL, Zhu W. Ifenprodil induced antinociception and decreased the expression of NR2B subunits in the dorsal horn after chronic dorsal root ganglia compression in rats. Anesth. Analg. 108, 1015-1020 (2009).
109. Gu X, Zhang J, Ma Z et al. The role of N-methyl-D-aspartate receptor subunit NR2B in spinal cord in cancer pain. Eur. J. Pain 14, 496-502 (2010).
110. Nakazato E, Kato A, Watanabe S. Brain but not spinal NR2B receptor is responsible for the anti-allodynic effect of an NR2B subunit-selective antagonist CP-101,606 in a rat chronic constriction injury model. Pharmacology 73, 8-14 (2005). (Pubitemid 39664216)
111. Gingrich JR, Pelkey KA, Fam SR et al. Unique domain anchoring of Src to synaptic NMDA receptors via the mitochondrial protein NADH dehydrogenase subunit 2. Proc. Natl Acad. Sci. USA 101, 6237-6242 (2004). (Pubitemid 38520558)
112. Correll GE, Maleki J, Gracely EJ, Muir JJ, Harbut RE. Subanesthetic ketamine infusion therapy: a retrospective analysis of a novel therapeutic approach to complex regional pain syndrome. Pain Med. 5, 263-275 (2004). (Pubitemid 39369246)
113. Kiefer RT, Rohr P, Ploppa A et al. Efficacy of ketamine in anesthetic dosage for the treatment of refractory complex regional pain syndrome: an open-label Phase II study. Pain Med. 9, 1173-1201 (2008).
114. Duale C, Sibaud F, Guastella V et al. Perioperative ketamine does not prevent chronic pain after thoracotomy. Eur. J. Pain 13, 497-505 (2009).
115. Huge V, Lauchart M, Magerl W et al. Effects of low-dose intranasal (S)-ketamine in patients with neuropathic pain. Eur. J. Pain 14, 387-394 (2010).
116. Nelson KA, Park KM, Robinovitz E, Tsigos C, Max MB. High-dose oral dextromethorphan versus placebo in painful diabetic neuropathy and postherpetic neuralgia. Neurology 48, 1212-1218 (1997). (Pubitemid 27240536)
117. Pud D, Eisenberg E, Spitzer A et al. The NMDA receptor antagonist amantadine reduces surgical neuropathic pain in cancer patients: a double blind, randomized, placebo controlled trial. Pain 75, 349-354 (1998). (Pubitemid 28160146)
118. Fukui S, Komoda Y, Nosaka S. Clinical application of amantadine, an NMDA antagonist, for neuropathic pain. J. Anesth. 15, 179-181 (2001). (Pubitemid 32899064)
119. Schwartzman RJ, Alexander GM, Grothusen JR et al. Outpatient intravenous ketamine for the treatment of complex regional pain syndrome: a double-blind placebo controlled study. Pain 147, 107-115 (2009).
120. Sigtermans MJ, van Hilten JJ, Bauer MC et al. Ketamine produces effective and long-term pain relief in patients with complex regional pain syndrome type 1. Pain 145, 304-311 (2009).
121. Leung A, Wallace MS, Ridgeway B, Yaksh T. Concentration-effect relationship of intravenous alfentanil and ketamine on peripheral neurosensory thresholds, allodynia and hyperalgesia of neuropathic pain. Pain 91, 177-187 (2001). (Pubitemid 32279619)
122. Sinis N, Birbaumer N, Gustin S et al. Memantine treatment of complex regional pain syndrome: a preliminary report of six cases. Clin. J. Pain 23, 237-243 (2007).
123. Sang CN, Booher S, Gilron I, Parada S, Max MB. Dextromethorphan and memantine in painful diabetic neuropathy and postherpetic neuralgia: efficacy and dose-response trials. Anesthesiology 96, 1053-1061 (2002). (Pubitemid 34462564)
124. Wiech K, Kiefer RT, Topfner S et al. A placebo-controlled randomized crossover trial of the N-methyl-D-aspartic acid receptor antagonist, memantine, in patients with chronic phantom limb pain. Anesth. Analg. 98, 408-413 (2004). (Pubitemid 38129389)
125. Schifitto G, Yiannoutsos CT, Simpson DM et al. A placebo-controlled study of memantine for the treatment of human immunodeficiency virus-associated sensory neuropathy. J. Neurovirol. 12, 328-331 (2006). (Pubitemid 44382984)
126. Wallace MS, Rowbotham MC, Katz NP et al. A randomized, double-blind, placebo-controlled trial of a glycine antagonist in neuropathic pain. Neurology 59, 1694-1700 (2002). (Pubitemid 35424448)
127. Amr YM. Multi-day low dose ketamine infusion as adjuvant to oral gabapentin in spinal cord injury related chronic pain: a prospective, randomized, double blind trial. Pain Physician 13, 245-249 (2010).
128. Mercadante S, Arcuri E, Tirelli W, Casuccio A. Analgesic effect of intravenous ketamine in cancer patients on morphine therapy: a randomized, controlled, double-blind, crossover, double-dose study. J. Pain Symptom. Manage. 20, 246-252 (2000).
129. Bettini E, Sava A, Griffante C et al. Identification and characterisation of novel NMDA receptor antagonists selective for NR2A- over NR2βcontaining receptors. J. Pharmacol. Exp. Ther. 335, 636-644 (2010).
130. Costa BM, Irvine MW, Feng G et al. A novel family of negative and positive allosteric modulators of NMDA receptors. J. Pharmacol. Exp. Ther. 335, 614-621 (2010).