Neuropathic pain depends upon d-serine co-activation of spinal NMDA receptors in rats
Neuroscience Letters. 2015-08-01; 603: 42-47
DOI: 10.1016/j.neulet.2015.07.010
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1. Neurosci Lett. 2015 Aug 31;603:42-7. doi: 10.1016/j.neulet.2015.07.010. Epub 2015
Jul 13.
Neuropathic pain depends upon D-serine co-activation of spinal NMDA receptors in
rats.
Lefèvre Y(1), Amadio A(1), Vincent P(1), Descheemaeker A(2), Oliet SH(1), Dallel
R(2), Voisin DL(3).
Author information:
(1)Neurocentre Magendie, Inserm U862, F-33000 Bordeaux, France; Univ. Bordeaux,
F-33000 Bordeaux, France.
(2)Clermont Université, Université d’Auvergne, NEURO-DOL, BP 10448, F-63000
Clermont-Ferrand, Inserm, U1107, F-63001 Clermont-Ferrand, France.
(3)Neurocentre Magendie, Inserm U862, F-33000 Bordeaux, France; Univ. Bordeaux,
F-33000 Bordeaux, France. Electronic address: .
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.
Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
DOI: 10.1016/j.neulet.2015.07.010
PMID: 26182881 [Indexed for MEDLINE]