ArticleThe Journal of clinical investigation2018
Ca2+-binding protein NECAB2 facilitates inflammatory pain hypersensitivity.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 32 citations in OpenAlex.
- Persistent interferon signaling causes sensory neuron plasticity and pain before and during arthritis.Nature neuroscience · 2026Article
- Botulinum toxin type A inhibits microglia pyroptosis by suppressing Cblb-mediated degradation of Pdlim1 to attenuate neuropathic pain.The journal of headache and pain · 2025Article
- Investigating the Causality and Pathogenesis of Primary Sclerosing Cholangitis in Colorectal Cancer Through Mendelian Randomization and Bioinformatics.Genetics research · 2025Article
- Depression Treatment: Is There a Role for Botulinum Toxin Type A?Microorganisms · 2024Review
- Advancements in Single-Cell RNA Sequencing and Spatial Transcriptomics for Central Nervous System Disease.Cellular and molecular neurobiology · 2024Review
- Botulinum toxin type A-targeted SPP1 contributes to neuropathic pain by the activation of microglia pyroptosis.World journal of psychiatry · 2024Article
- Integration of selective sweeps across the sheep genome: understanding the relationship between production and adaptation traits.Genetics, selection, evolution : GSE · 2024Article
- Direct comparison of Hoxb8-driven reporter distribution in the brains of four transgenic mouse lines: towards a spinofugal projection atlas.Frontiers in neuroanatomy · 2024Article
- A human TRPV1 genetic variant within the channel gating domain regulates pain sensitivity in rodents.The Journal of clinical investigation · 2023Article
- Engineering 2D Silicene-Based Mesoporous Nanomedicine for In Vivo Near-Infrared-Triggered Analgesia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Huc-MSCs-derived exosomes attenuate inflammatory pain by regulating microglia pyroptosis and autophagy via the miR-146a-5p/TRAF6 axis.Journal of nanobiotechnology · 2022Article
- Autism-Risk GeneFrontiers in molecular neuroscience · 2022Article
- BRD4 Inhibition Attenuates Inflammatory Pain by Ameliorating NLRP3 Inflammasome-Induced Pyroptosis.Frontiers in immunology · 2022Article
- Locomotor deficits in a mouse model of ALS are paralleled by loss of V1-interneuron connections onto fast motor neurons.Nature communications · 2021Article
- NECAB1 and NECAB2 are Prevalent Calcium-Binding Proteins of CB1/CCK-Positive GABAergic Interneurons.Cerebral cortex (New York, N.Y. : 1991) · 2021Article
- Article
- Postnatal Developmental Expression Profile Classifies the Indusium Griseum as a Distinct Subfield of the Hippocampal Formation.Frontiers in cell and developmental biology · 2020Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
Abstract
Pain signals are transmitted by multisynaptic glutamatergic pathways. Their first synapse between primary nociceptors and excitatory spinal interneurons gates the sensory load. In this pathway, glutamate release is orchestrated by Ca2+-sensor proteins, with N-terminal EF-hand Ca2+-binding protein 2 (NECAB2) being particular abundant. However, neither the importance of NECAB2+ neuronal contingents in dorsal root ganglia (DRGs) and spinal cord nor the function determination by NECAB2 has been defined. A combination of histochemical analyses and single-cell RNA-sequencing showed NECAB2 in small- and medium-sized C- and Aδ D-hair low-threshold mechanoreceptors in DRGs, as well as in protein kinase C γ excitatory spinal interneurons. NECAB2 was downregulated by peripheral nerve injury, leading to the hypothesis that NECAB2 loss of function could limit pain sensation. Indeed, Necab2-/- mice reached a pain-free state significantly faster after peripheral inflammation than did WT littermates. Genetic access to transiently activated neurons revealed that a mediodorsal cohort of NECAB2+ neurons mediates inflammatory pain in the mouse spinal dorsal horn. Here, besides dampening excitatory transmission in spinal interneurons, NECAB2 limited pronociceptive brain-derived neurotrophic factor (BDNF) release from sensory afferents. Hoxb8-dependent reinstatement of NECAB2 expression in Necab2-/- mice then demonstrated that spinal and DRG NECAB2 alone could control inflammation-induced sensory hypersensitivity. Overall, we identify NECAB2 as a critical component of pronociceptive pain signaling, whose inactivation offers substantial pain relief.
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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.