- •Spinal N-methyl-D-aspartate receptors play a key role in the development of central sensitization.
- •D-serine modulated spinal protein kinase C-dependent (Ser896) phosphorylation of GluN1 subunit.
- •D-serine mediated the effects of spinal sigma-1 receptors on phosphorylated GluN1 and nociception.
- •D-serine contributed to the development of mechanical allodynia after peripheral nerve injury.
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
- The σ-1 receptor interacts directly with GluN1 but not GluN2A in the GluN1/GluN2A NMDA receptor.J Neurosci. 2013; 33: 18219-18224
- Mechanisms of disease: neuropathic pain—a clinical perspective.Nat Clin Pract Neurol. 2006; 2: 95-106
- A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man.Pain. 1988; 33: 87-107
- Protein kinase C reduces Mg2+ block of NMDA-receptor channels as a mechanism of modulation.Nature. 1992; 356: 521-523
- Spinal sigma-1 receptors activate NADPH oxidase 2 leading to the induction of pain hypersensitivity in mice and mechanical allodynia in neuropathic rats.Pharmacol Res. 2013; 74: 56-67
- Astrocyte sigma-1 receptors modulate connexin 43 expression leading to the induction of below-level mechanical allodynia in spinal cord injured mice.Neuropharmacology. 2016; 111: 34-46
- D-serine in glia and neurons derives from 3-phosphoglycerate dehydrogenase.J Neurosci. 2013; 33: 12464-12469
- Decrease in N-methyl-D-aspartic acid receptor-NR2B subunit levels by intrathecal short-hairpin RNA blocks group I metabotropic glutamate receptor-mediated hyperalgesia.J Pharmacol Exp Ther. 2007; 322: 186-194
- A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia.Pain. 1988; 32: 77-88
- Intrathecal morphine in mice: A new technique.Eur J Pharmacol. 1980; 67: 313-316
- Intrathecal treatment with sigma1 receptor antagonists reduces formalin-induced phosphorylation of NMDA receptor subunit 1 and the second phase of formalin test in mice.Br J Pharmacol. 2006; 148: 490-498
- Activation of the spinal sigma-1 receptor enhances NMDA-induced pain via PKC- and PKA-dependent phosphorylation of the NR1 subunit in mice.Br J Pharmacol. 2008; 154: 1125-1134
- Up-regulation of NMDAR1 subunit gene expression in cortical neurons via a PKA-dependent pathway.J Neurochem. 2004; 88: 564-575
- Neuropathic pain depends upon D-serine co-activation of spinal NMDA receptors in rats.Neurosci Lett. 2015; 603: 42-47
- The sigma-1 receptor modulates NMDA receptor synaptic transmission and plasticity via SK channels in rat hippocampus.J Physiol. 2007; 578: 143-157
- D-Serine and glycine differentially control neurotransmission during visual cortex critical period.PLoS One. 2016; 11: e0151233
- Glycine inhibitory dysfunction turns touch into pain through astrocyte-derived D-serine.Pain. 2011; 152: 1340-1348
- Serine racemase is predominantly localized in neurons in mouse brain.J Comp Neurol. 2008; 510: 641-654
- Spinal sigma-1 receptor activation increases the production of D-serine in astrocytes which contributes to the development of mechanical allodynia in a mouse model of neuropathic pain.Pharmacol Res. 2015; 100: 353-364
- σ1 Receptors activate astrocytes via p38 MAPK phosphorylation leading to the development of mechanical allodynia in a mouse model of neuropathic pain.Br J Pharmacol. 2014; 171: 5881-5897
- Sigma-1 receptor-mediated increase in spinal p38 MAPK phosphorylation leads to the induction of mechanical allodynia in mice and neuropathic rats.Exp Neurol. 2013; 247: 383-391
- Glycinergic mediation of tactile allodynia induced by platelet-activating factor (PAF) through glutamate-NO-cyclic GMP signalling in spinal cord in mice.Pain. 2008; 138: 525-536
- D-serine is an endogenous ligand for the glycine site of the N-methyl-D-aspartate receptor.Proc Natl Acad Sci U S A. 2000; 97: 4926-4931
- NMDA receptors are upregulated and trafficked to the plasma membrane after sigma-1 receptor activation in the rat hippocampus.J Neurosci. 2014; 34: 11325-11338
- Synaptic and extrasynaptic NMDA receptors are gated by different endogenous coagonists.Cell. 2012; 150: 633-646
- Neurogenic pain and steroid synthesis in the spinal cord.J Mol Neurosci. 2006; 28: 17-31
- Impact of neuropathic pain on the gene expression and activity of cytochrome P450side-chain-cleavage in sensory neural networks.Cell Mol Life Sci. 2004; 61: 2274-2284
- Peripheral neuropathy and neurosteroid formation in the central nervous system.Brain Res Rev. 2008; 57: 454-459
- Glutamate receptor modulation by protein phosphorylation.J Physiol Paris. 1994; 88: 181-192
- Spinal neuronal NOS activation mediates sigma-1 receptor-induced mechanical and thermal hypersensitivity in mice: involvement of PKC-dependent GluN1 phosphorylation.Br J Pharmacol. 2011; 163: 1707-1720
- Intrathecal administration of sigma-1 receptor agonists facilitates nociception: involvement of a protein kinase C-dependent pathway.J Neurosci Res. 2008; 86: 3644-3654
- Intrathecal injection of the sigma(1) receptor antagonist BD1047 blocks both mechanical allodynia and increases in spinal NR1 expression during the induction phase of rodent neuropathic pain.Anesthesiology. 2008; 109: 879-889
- Sigma-1 receptor-induced increase in murine spinal NR1 phosphorylation is mediated by the PKCalpha and epsilon, but not the PKCzeta, isoforms.Neurosci Lett. 2010; 477: 95-99
- Coordinated PKA and PKC phosphorylation suppresses RXR-mediated ER retention and regulates the surface delivery of NMDA receptors.Neuropharmacology. 2003; 45: 755-767
- The sigma-1 receptor chaperone as an inter-organelle signalipng modulator.Trends Pharmacol Sci. 2010; 31: 557-566
- When the endogenous hallucinogenic trace amine N,N-dimethyltryptamine meets the sigma-1 receptor.Sci Signal. 2009; 2: pe12
- Spinal NMDA receptor phosphorylation correlates with the presence of neuropathic signs following peripheral nerve injury in the rat.Neurosci Lett. 2006; 399: 85-90
- Identification of PKC-isoform-specific biological actions using pharmacological approaches.Trends Pharmacol Sci. 2000; 21: 181-187
- Serine racemase: A glial enzyme synthesizing D-serine to regulate glutamate-N-methyl-D-aspartate neurotransmission.Proc Natl Acad Sci U S A. 1999; 96: 13409-13414
- Evidence for a central component of post-injury pain hypersensitivity.Nature. 1983; 306: 686-688
- Neuropathic pain: Aetiology, symptoms, mechanisms, and management.Lancet. 1999; 353: 1959-1964
- Modulation of NMDA- and (+)TAN-67-induced nociception by GABA(B) receptors in the mouse spinal cord.Life Sci. 2000; 68: 719-725
- An increase in spinal dehydroepiandrosterone sulfate (DHEAS) enhances NMDA-induced pain via phosphorylation of the NR1 subunit in mice: Involvement of the sigma-1 receptor.Neuropharmacology. 2010; 59: 460-467
- Involvement of sigma-1 receptor in astrocyte activation induced by methamphetamine via up-regulation of its own expression.J Neuroinflammation. 2015; 12: 29
S.-R.C. and J.-Y.M. contributed equally to this work.
This work was supported by the National Research Foundation of Korea grant funded by the Korean Government (grant 2014R1A2A2A01007695 ).
The authors have no conflicts of interest to declare.