ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Synaptic GluN2A and GluN2B containing NMDA receptors within the superficial dorsal horn activated following primary afferent stimulation.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Qualitative review on N-methyl-D-aspartate receptor expression in rat spinal cord during the postnatal development: Implications for central sensitization and pain.Developmental neurobiology · 2020Pooled it
- RIN1 regulates developmental and pain-related plasticity in spinal synapses via NMDA receptor subunit trafficking.PLoS biology · 2025Article
- Synapse-specific diversity of distinct postsynaptic GluN2 subtypes defines transmission strength in spinal lamina I.Frontiers in synaptic neuroscience · 2023Article
- Activation of Meningeal Afferents Relevant to Trigeminal Headache Pain after Photothrombotic Stroke Lesion: A Pilot Study in Mice.International journal of molecular sciences · 2022Article
- Targeted ubiquitination of sensory neuron calcium channels reduces the development of neuropathic pain.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Modulation of NMDA receptor activity by CR4056, an imidazoline-2 receptor ligand with analgesic properties.Frontiers in pain research (Lausanne, Switzerland) · 2022Article
- Advances and Barriers in Understanding PresynapticFrontiers in molecular neuroscience · 2022Review
- Differential expression of GluN2 NMDA receptor subunits in the dorsal horn of male and female rats.Channels (Austin, Tex.) · 2021Article
- CaMKII binding to GluN2B at S1303 has no role in acute or inflammatory pain.Brain research · 2021Article
- Conserved contributions of NMDA receptor subtypes to synaptic responses in lamina II spinal neurons across early postnatal development.Molecular brain · 2020Article
- Agmatine preferentially antagonizes GluN2B-containing N-methyl-d-aspartate receptors in spinal cord.Journal of neurophysiology · 2019Article
- NMDA Receptor Activation Underlies the Loss of Spinal Dorsal Horn Neurons and the Transition to Persistent Pain after Peripheral Nerve Injury.Cell reports · 2018Article
- Effects of intrathecal bupivacaine on the NR2B/CaMKIIα/CREB signaling pathway in the rat lumbar spinal cord.Molecular medicine reports · 2018Article
- Inhibition Mediated by Glycinergic and GABAergic Receptors on Excitatory Neurons in Mouse Superficial Dorsal Horn Is Location-Specific but Modified by Inflammation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- β-arrestin-2 regulates NMDA receptor function in spinal lamina II neurons and duration of persistent pain.Nature communications · 2016Article
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- Hunting for origins of migraine pain: cluster analysis of spontaneous and capsaicin-induced firing in meningeal trigeminal nerve fibers.Frontiers in cellular neuroscience · 2015Article
- Article
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2 authors at 1 institution in 1 country.
Funding
Abstract
NMDA receptors are important elements in pain signaling in the spinal cord dorsal horn. They are heterotetramers, typically composed of two GluN1 and two of four GluN2 subunits: GluN2A-2D. Mice lacking some of the GluN2 subunits show deficits in pain transmission yet functional synaptic localization of these receptor subtypes in the dorsal horn has not been fully resolved. In this study, we have investigated the composition of synaptic NMDA receptors expressed in monosynaptic and polysynaptic pathways from peripheral sensory fibers to lamina I neurons in rats. We focused on substance P receptor-expressing (NK1R+) projection neurons, critical for expression of hyperalgesia and allodynia. EAB-318 and (R)-CPP, GluN2A/B antagonists, blocked both monosynaptic and polysynaptic NMDA EPSCs initiated by primary afferent activation by ∼90%. Physiological measurements exploiting the voltage dependence of monosynaptic EPSCs similarly indicated dominant expression of GluN2A/B types of synaptic NMDA receptors. In addition, at synapses between C fibers and NK1R+ neurons, NMDA receptor activation initiated a secondary, depolarizing current. Ifenprodil, a GluN2B antagonist, caused modest suppression of monosynaptic NMDA EPSC amplitudes, but had a widely variable, sometimes powerful, effect on polysynaptic responses following primary afferent stimulation when inhibitory inputs were blocked to mimic neuropathic pain. We conclude that GluN2B subunits are moderately expressed at primary afferent synapses on lamina I NK1R+ neurons, but play more important roles for polysynaptic NMDA EPSCs driven by primary afferents following disinhibition, supporting the view that the analgesic effect of the GluN2B antagonist on neuropathic pain is at least in part, within the spinal cord.
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