ArticleNeuroscience2011
Selective knockdown of NMDA receptors in primary afferent neurons decreases pain during phase 2 of the formalin test.
Article in Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 49 citations in OpenAlex.
- Glial cells in neuropathic pain.Physiological reviews · 2026Review
- LRRC8A constitutively inhibits pain hypersensitivity in rodent models by restraining NMDA receptor activity at spinal cord synapses.Science translational medicine · 2025Article
- α2δ-1-Linked NMDA and AMPA Receptors in Neuropathic Pain and Gabapentinoid Action.Journal of neurochemistry · 2025Review
- Roles of Phosphorylation of N-Methyl-D-Aspartate Receptor in Chronic Pain.Cellular and molecular neurobiology · 2023Review
- Advances and Barriers in Understanding PresynapticFrontiers in molecular neuroscience · 2022Review
- α2δ-1 Upregulation in Primary Sensory Neurons Promotes NMDA Receptor-Mediated Glutamatergic Input in Resiniferatoxin-Induced Neuropathy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Lyophilization Serves as an Effective Strategy for Drug Development of the α9α10 Nicotinic Acetylcholine Receptor Antagonist α-Conotoxin GeXIVA[1,2].Marine drugs · 2021Article
- CaMKII binding to GluN2B at S1303 has no role in acute or inflammatory pain.Brain research · 2021Article
- Calcineurin Inhibition Causes α2δ-1-Mediated Tonic Activation of Synaptic NMDA Receptors and Pain Hypersensitivity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Levo-corydalmine Attenuates Vincristine-Induced Neuropathic Pain in Mice by Upregulating the Nrf2/HO-1/CO Pathway to Inhibit Connexin 43 Expression.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2020Article
- Presynaptic NMDA receptors control nociceptive transmission at the spinal cord level in neuropathic pain.Cellular and molecular life sciences : CMLS · 2019Review
- Distinct Modes of Presynaptic Inhibition of Cutaneous Afferents and Their Functions in Behavior.Neuron · 2019Article
- Endogenous Glutamate Excites Myenteric Calbindin Neurons by Activating Group I Metabotropic Glutamate Receptors in the Mouse Colon.Frontiers in neuroscience · 2019Article
- Increased α2δ-1-NMDA receptor coupling potentiates glutamatergic input to spinal dorsal horn neurons in chemotherapy-induced neuropathic pain.Journal of neurochemistry · 2019Article
- Attenuation Effects of Alpha-Pinene Inhalation on Mice with Dizocilpine-Induced Psychiatric-Like Behaviour.Evidence-based complementary and alternative medicine : eCAM · 2019Article
- The Contribution of NMDA Receptors in Antinociceptive Effect of Pregabalin: Comparison of Two Models of Pain Assessment.Anesthesiology and pain medicine · 2017Article
- Antinociceptive Activity ofFrontiers in pharmacology · 2017Article
- Analgesic Effects of Danggui-Shaoyao-San on Various "Phenotypes" of Nociception and Inflammation in a Formalin Pain Model.Molecular neurobiology · 2016Article
- The Role of NMDARs Ligands on Antinociceptive Effects of Pregabalin in the Tail Flick Test.Anesthesiology and pain medicine · 2015Article
- Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The role of NMDA receptors (NMDARs) expressed by primary afferent neurons in nociception remains controversial. The aim of this study was to develop mice with a tissue selective knockdown of NMDARs in these neurons and to evaluate their behavioral responses to different types of painful stimuli. Mice with floxed NMDAR NR1 subunit gene (fNR1) were crossed with mice expressing Cre recombinase under the control of the peripherin promotor (Prph-Cre). Male Prph-Cre+ floxed NR1 mice were compared to Cre- littermates. Both quantitative RT/PCR and Western blotting indicated a ∼75% reduction in NR1 expression in dorsal root ganglia (DRG) extracts with no effect on NR1 expression in spinal cord, brain or the enteric nervous system. Immunocytochemistry with antibodies to NR1 revealed decreased staining in all size classes of DRG neurons. NMDA produced a detectable increase in [Ca2+]i in 60% of DRG neurons cultured from Cre- mice, but only 15% of those from Cre+ mice. Furthermore, the peak [Ca2+]i responses were 64% lower in neurons from Cre+ mice. There was no significant difference between Cre+ and Cre- mice in response latencies to the hotplate or tail withdrawal tests of thermal nociception, nor was there a difference in withdrawal thresholds to mechanical stimuli of the tail or paw. However, compared to Cre- littermates, Cre+ knockdown mice had a 50% decrease in the phase 2 response to formalin injection (P<0.001). There was no effect on phase 1 responses. These results suggest that NMDA receptors expressed by primary afferent nerves play an important role in the development of sensitized pain states.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.