title: Neuropathic pain depends upon D-serine co-activation of spinal NMDA receptors in rats.
abstract: Activation of N-methyl-d-aspartate (NMDA) receptors is critical for hypersensitivity in chronic neuropathic pain. Since astroglia can regulate NMDA receptor activation by releasing the NMDA receptor co-agonist d-serine, we investigated the role of NMDA receptor and d-serine in neuropathic chronic pain. Male Wistar rats underwent right L5-L6 spinal nerve ligation or sham surgery and were tested for mechanical allodynia and hyperalgesia after 14 days. Acute intrathecal administration of the NMDA receptor antagonist d-AP5 as well as chronic administration of the glia metabolism inhibitor fluoroacetate significantly reduced mechanical allodynia in neuropathic rats. The effect of fluoroacetate was reversed by acutely administered intrathecal d-serine. Degrading d-serine using acute intrathecal administration of d-aminoacid oxidase also reduced pain symptoms. Immunocytochemistry showed that about 70% of serine racemase, the synthesizing enzyme of d-serine, was expressed in astrocyte processes in the superficial laminae of L5 dorsal horn. Serine racemase expression was upregulated in astrocyte processes in neuropathic rats compared to sham rats. These results show that neuropathic pain depends upon glial d-serine that co-activates spinal NMDA receptors.
authors.affiliation: Neurocentre Magendie, Inserm U862, F-33000 Bordeaux, France; Univ. Bordeaux, F-33000 Bordeaux, France.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lefèvre
authors.affiliation: Neurocentre Magendie, Inserm U862, F-33000 Bordeaux, France; Univ. Bordeaux, F-33000 Bordeaux, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Amadio
authors.affiliation: Neurocentre Magendie, Inserm U862, F-33000 Bordeaux, France; Univ. Bordeaux, F-33000 Bordeaux, France.
authors.forename: Peggy
authors.initials: P
authors.lastname: Vincent
authors.affiliation: Clermont Université, Université d'Auvergne, NEURO-DOL, BP 10448, F-63000 Clermont-Ferrand, Inserm, U1107, F-63001 Clermont-Ferrand, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Descheemaeker
authors.affiliation: Neurocentre Magendie, Inserm U862, F-33000 Bordeaux, France; Univ. Bordeaux, F-33000 Bordeaux, France.
authors.forename: Stéphane H R
authors.initials: SH
authors.lastname: Oliet
authors.affiliation: Clermont Université, Université d'Auvergne, NEURO-DOL, BP 10448, F-63000 Clermont-Ferrand, Inserm, U1107, F-63001 Clermont-Ferrand, France.
authors.forename: Radhouane
authors.initials: R
authors.lastname: Dallel
authors.affiliation: Neurocentre Magendie, Inserm U862, F-33000 Bordeaux, France; Univ. Bordeaux, F-33000 Bordeaux, France. Electronic address: daniel.voisin@inserm.fr.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Voisin
mesh_terms: D000818:Animals; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006930:Hyperalgesia / Q000503:physiopathology; D008297:Male; D009437:Neuralgia / Q000378:metabolism* / Q000503:physiopathology; D010812:Physical Stimulation; D019998:Racemases and Epimerases / Q000378:metabolism; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism*; D014110:Touch; D000099300:Serine Racemase
chemical_list: D005904:Glial Fibrillary Acidic Protein; D019998:Racemases and Epimerases; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; D000099300:Serine Racemase
keywords: Astrocyte; NMDA receptor; Neuropathic pain; d-Serine