title: D-aspartate modulates nociceptive-specific neuron activity and pain threshold in inflammatory and neuropathic pain condition in mice.
abstract: D-Aspartate (D-Asp) is a free D-amino acid found in the mammalian brain with a temporal-dependent concentration based on the postnatal expression of its metabolizing enzyme D-aspartate oxidase (DDO). D-Asp acts as an agonist on NMDA receptors (NMDARs). Accordingly, high levels of D-Asp in knockout mice for Ddo gene (Ddo (-/-)) or in mice treated with D-Asp increase NMDAR-dependent processes. We have here evaluated in Ddo (-/-) mice the effect of high levels of free D-Asp on the long-term plastic changes along the nociceptive pathway occurring in chronic and acute pain condition. We found that Ddo (-/-) mice show an increased evoked activity of the nociceptive specific (NS) neurons of the dorsal horn of the spinal cord (L4-L6) and a significant decrease of mechanical and thermal thresholds, as compared to control mice. Moreover, Ddo gene deletion exacerbated the nocifensive responses in the formalin test and slightly reduced pain thresholds in neuropathic mice up to 7 days after chronic constriction injury. These findings suggest that the NMDAR agonist, D-Asp, may play a role in the regulation of NS neuron electrophysiological activity and behavioral responses in physiological and pathological pain conditions.
authors: Pharmacology Division, Department of Experimental Medicine, The Second University of Naples, Via Costantinopoli 16, 80138 Naples, Italy.
authors: Serena
authors: S
authors: Boccella
authors: CNR, National Research Council, Cell Biology and Neurobiology Institute, Roma, Italy ; IRCCS, Santa Lucia Foundation, Rome, Italy.
authors: Valentina
authors: V
authors: Vacca
authors: Laboratory of Behavioural Neuroscience, Ceinge Biotecnologie Avanzate, Via G. Salvatore 486, 80145 Naples, Italy ; Department of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II", Naples, Italy.
authors: Francesco
authors: F
authors: Errico
authors: CNR, National Research Council, Cell Biology and Neurobiology Institute, Roma, Italy ; IRCCS, Santa Lucia Foundation, Rome, Italy.
authors: Sara
authors: S
authors: Marinelli
authors: Laboratory of Behavioural Neuroscience, Ceinge Biotecnologie Avanzate, Via G. Salvatore 486, 80145 Naples, Italy.
authors: Marta
authors: M
authors: Squillace
authors: Pharmacology Division, Department of Experimental Medicine, The Second University of Naples, Via Costantinopoli 16, 80138 Naples, Italy.
authors: Francesca
authors: 0000-0003-0759-9602
authors: F
authors: Guida
authors: Laboratory of Behavioural Neuroscience, Ceinge Biotecnologie Avanzate, Via G. Salvatore 486, 80145 Naples, Italy.
authors: Anna
authors: A
authors: Di Maio
authors: Laboratory of Behavioural Neuroscience, Ceinge Biotecnologie Avanzate, Via G. Salvatore 486, 80145 Naples, Italy.
authors: Daniela
authors: D
authors: Vitucci
authors: Department of Anaesthesiology, Surgery and Emergency, The Second University of Naples, Naples, Italy.
authors: Enza
authors: E
authors: Palazzo
authors: Pharmacology Division, Department of Experimental Medicine, The Second University of Naples, Via Costantinopoli 16, 80138 Naples, Italy.
authors: Vito
authors: V
authors: De Novellis
authors: Pharmacology Division, Department of Experimental Medicine, The Second University of Naples, Via Costantinopoli 16, 80138 Naples, Italy.
authors: Sabatino
authors: S
authors: Maione
authors: CNR, National Research Council, Cell Biology and Neurobiology Institute, Roma, Italy ; IRCCS, Santa Lucia Foundation, Rome, Italy.
authors: Flaminia
authors: F
authors: Pavone
authors: Laboratory of Behavioural Neuroscience, Ceinge Biotecnologie Avanzate, Via G. Salvatore 486, 80145 Naples, Italy ; Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, The Second University of Naples, Naples, Italy.
authors: Alessandro
authors: A
authors: Usiello
mesh_terms: D000818:Animals; D050804:D-Aspartate Oxidase / Q000172:deficiency / Q000378:metabolism; D026603:D-Aspartic Acid / Q000494:pharmacology*; D005260:Female; D017353:Gene Deletion; D007249:Inflammation / Q000473:pathology*; D007837:Latency Period, Psychological; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009437:Neuralgia / Q000473:pathology* / Q000503:physiopathology*; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D059225:Nociception / Q000187:drug effects*; D017288:Pain Threshold / Q000187:drug effects*; D013696:Temperature; D013997:Time Factors
chemical_list: D026603:D-Aspartic Acid; D050804:D-Aspartate Oxidase
references: Comp Biochem Physiol B. 1993 Jul-Aug;105(3-4):731-4
references: 8103425
references: Neurosci Lett. 1999 Jan 29;260(2):89-92
references: 10025706
references: Pain. 2009 Sep;145(1-2):219-29
references: 19608345
references: Annu Rev Neurosci. 2009;32:1-32
references: 19400724
references: Neuroscience. 2000;100(1):183-9
references: 10996468
references: Neurobiol Aging. 2011 Dec;32(12):2229-43
references: 20097447
references: Neuroscience. 1988 Jul;26(1):17-31
references: 2901691
references: Pain Med. 2010 Nov;11(11):1726-42
references: 21044263
references: Brain Res. 1998 Oct 12;808(1):65-71
references: 9795139
references: Acta Physiol (Oxf). 2008 Mar;192(3):421-7
references: 17970830
references: Anesth Analg. 1995 Jan;80(1):173-9
references: 7802274
references: Pain. 2010 Jan;148(1):26-35
references: 19879047
references: Prog Neurobiol. 1993 Nov;41(5):565-607
references: 8284437
references: J Neurosci. 2008 Oct 8;28(41):10404-14
references: 18842900
references: Neurobiol Aging. 2011 Nov;32(11):2061-74
references: 20031274
references: Clin J Pain. 2000 Jun;16(2 Suppl):S73-9
references: 10870744
references: Pain. 1977 Dec;4(2):161-74
references: 564014
references: Mol Cell Neurosci. 2008 Feb;37(2):236-46
references: 17981050
references: Sheng Li Xue Bao. 2008 Oct 25;60(5):635-44
references: 18958372
references: Mol Pain. 2012;8:60
references: 22913292
references: Pain. 1992 Oct;51(1):5-17
references: 1454405
references: Proc Natl Acad Sci U S A. 1984 Nov;81(21):6876-80
references: 6149551
references: Exp Neurol. 2011 Dec;232(2):240-50
references: 21946266
references: Pain. 2014 Feb;155(2):388-402
references: 24231652
references: Amino Acids. 2012 Nov;43(5):1861-71
references: 22851050
references: Biophys J. 2001 May;80(5):2152-66
references: 11325718
references: Pain. 2000 Nov;88(2):113-8
references: 11050365
references: Biochim Biophys Acta. 1991 Jan 23;1073(1):203-8
references: 1991137
references: Pain Manag. 2011 May;1(3):229-38
references: 24646389
references: J Neurosci. 2006 Apr 19;26(16):4308-17
references: 16624951
references: Mol Pain. 2010;6:14
references: 20205719
references: Pain. 1988 Apr;33(1):87-107
references: 2837713
references: Brain Behav Immun. 2013 Aug;32:40-50
references: 23402794
references: Gen Pharmacol. 1997 May;28(5):633-8
references: 9184794
references: Gene. 2006 Jun 7;374:50-7
references: 16516413
references: Brain Res. 1995 Apr 3;676(1):189-95
references: 7796169
references: J Neurochem. 1987 Jun;48(6):1699-708
references: 2883254
references: Physiol Rev. 2009 Apr;89(2):707-58
references: 19342617
references: PLoS One. 2012;7(10):e47977
references: 23110146
references: Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):2013-8
references: 9050896