D-Aspartate drinking solution alleviates pain and cognitive impairment in neuropathic mice.
D-Aspartate (D-Asp) is a free D-amino acid detected in multiple brain regions and putative precursor of endogenous N-methyl-D-aspartate (NMDA) acting as agonist at NMDA receptors. In this study, we investigated whether D-Asp (20 mM) in drinking solution for 1 month affects pain responses and pain-related emotional, and cognitive behaviour in a model of neuropathic pain induced by the spared nerve injury (SNI) of the sciatic nerve in mice. SNI mice developed mechanical allodynia and motor coordination impairment 30 days after SNI surgery. SNI mice showed cognitive impairment, anxiety and depression-like behaviour, reduced sociability in the three chamber sociability paradigm, increased expression of NR2B subunit of NMDA receptor and Homer 1a in the medial prefrontal cortex (mPFC). The expression of (post synaptic density) PSD-95 and Shank 1was instead unaffected in the mPFC of the SNI mice. Treatment with D-Asp drinking solution, started right after the SNI (day 0), alleviated mechanical allodynia, improved cognition and motor coordination and increased social interaction. D-Asp also restored the levels of extracellular D-Asp, Homer 1a and NR2B subunit of the NMDA receptor to physiological levels and reduced Shank1 and PSD-95 protein levels in the mPFC. Amitriptyline, a tricyclic antidepressant used also to alleviate neuropathic pain in humans, reverted mechanical allodynia and cognitive impairment, and unlike D-Asp, was effective in reducing depression and anxiety-like behaviour in the SNI mice and increased PSD protein level. Altogether these findings demonstrate that D-Asp improves sensorial, motor and cognitive-like symptoms related to chronic pain possibly through glutamate neurotransmission normalization in neuropathic mice.
Pharmacology Division, Department of Experimental Medicine, The Second University of Naples, via Costantinopoli 16, 80138, Naples, Italy.|Department of Anaesthesiology, Surgery and Emergency, The Second University of Naples, piazza Luigi Miraglia 2, 80138, Naples, Italy.
Enza
E
Palazzo
Pharmacology Division, Department of Experimental Medicine, The Second University of Naples, via Costantinopoli 16, 80138, Naples, Italy.
Livio
L
Luongo
Pharmacology Division, Department of Experimental Medicine, The Second University of Naples, via Costantinopoli 16, 80138, Naples, Italy.
Francesca
F
Guida
Pharmacology Division, Department of Experimental Medicine, The Second University of Naples, via Costantinopoli 16, 80138, Naples, Italy.
Ida
I
Marabese
Pharmacology Division, Department of Experimental Medicine, The Second University of Naples, via Costantinopoli 16, 80138, Naples, Italy.
Rosaria
R
Romano
Pharmacology Division, Department of Experimental Medicine, The Second University of Naples, via Costantinopoli 16, 80138, Naples, Italy.
Monica
M
Iannotta
Department of Woman, Child and of General and Specialist Surgery, Second University of Naples, Naples, Italy.
Francesca
F
Rossi
Pharmacology Division, Department of Experimental Medicine, The Second University of Naples, via Costantinopoli 16, 80138, Naples, Italy.|Neurobiology Laboratory, Zoological Station "A. Dohrn" Naples, Naples, Italy.
Antimo
A
D'Aniello
Pharmacology Division, Department of Experimental Medicine, The Second University of Naples, via Costantinopoli 16, 80138, Naples, Italy.
Luigi
L
Stella
Laboratory of Translational Psychiatry, Unit of Treatment Resistant Psychosis, Section of Psychiatry, Department of Neuroscience, University of Naples "Federico II", Naples, Italy.
Federica
F
Marmo
CEINGE, Biotecnologie Avanzate, Naples, Italy.
Alessandro
A
Usiello
Laboratory of Translational Psychiatry, Unit of Treatment Resistant Psychosis, Section of Psychiatry, Department of Neuroscience, University of Naples "Federico II", Naples, Italy.
Andrea
A
de Bartolomeis
Pharmacology Division, Department of Experimental Medicine, The Second University of Naples, via Costantinopoli 16, 80138, Naples, Italy. sabatino.maione@unina2.it.
Sabatino
S
Maione
Pharmacology Division, Department of Experimental Medicine, The Second University of Naples, via Costantinopoli 16, 80138, Naples, Italy.
Vito
V
de Novellis
D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology*; D060825:Cognitive Dysfunction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000076122:Disks Large Homolog 4 Protein / Q000378:metabolism; D000072233:Homer Scaffolding Proteins / Q000378:metabolism*; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D009437:Neuralgia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000473:pathology; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012584:Sciatic Nerve / Q000293:injuries* / Q000378:metabolism / Q000473:pathology
D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D000072233:Homer Scaffolding Proteins; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D001224:Aspartic Acid
D-Aspartate; Mechanical allodynia; Mice; NMDA receptor; Pain-related affective and cognitive behaviour; Spared nerve injury