ArticleScience advances2019
Sortilin gates neurotensin and BDNF signaling to control peripheral neuropathic pain.
Article in Science advances, 2019. 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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The trial behind it
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Who cites it
28 citing papers in PubMed, 60 citations in OpenAlex.
- The Hypothesis of Myelinodegeneration as an Initial Risk of Neuropathic Pain.Neuroscience bulletin · 2026Review
- Stage-specific transcriptomic alterations in the spinal cord reveal key regulatory genes and potential therapeutic targets in a rat model of neuropathic pain.Journal of translational medicine · 2025Article
- Review
- Neurotensin Regulates Primate Ovulation Via Multiple Neurotensin Receptors.Endocrinology · 2025Article
- Role of Exercise on Neuropathic Pain in Preclinical Models: Perspectives for Neuroglia.Molecular neurobiology · 2025Review
- Sortilin and L-type Calcium Channels May be Involved in the Unusual Mechanism of proBDNF Signaling in Regenerating Mouse Neuromuscular Junctions.Neurochemical research · 2025Article
- Decreased neurotensin induces ovulatory dysfunction via the NTSR1/ERK/EGR1 axis in polycystic ovary syndrome.Frontiers of medicine · 2025Article
- An atlas of neuropathic pain-associated molecular pathological characteristics in the mouse spinal cord.Communications biology · 2025Article
- Inhibition of sortilin reduces neuronal and vascular damage after ischemia/reperfusion through reduced inflammatory and autophagy actions in retinal Müller cells.Molecular vision · 2025Article
- Sortilin-Mediated Inhibition of TREK1/2 Channels in Primary Sensory Neurons Promotes Prediabetic Neuropathic Pain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- An anti-sortilin affibody-peptide fusion inhibits sortilin-mediated progranulin degradation.Frontiers in immunology · 2024Article
- In Ischemic Heart Disease, Reduced Sensitivity to Pressure at the Sternum Accompanies Lower Mortality after Five Years: Evidence from a Randomized Controlled Trial.Journal of clinical medicine · 2023Article
- Prospects of Using Chitosan-Based Biopolymers in the Treatment of Peripheral Nerve Injuries.International journal of molecular sciences · 2023Review
- Standardized Centella asiatica (ECa 233) extract decreased pain hypersensitivity development in a male mouse model of chronic inflammatory temporomandibular disorder.Scientific reports · 2023Article
- Dysfunction of inhibitory interneurons contributes to synaptic plasticity via GABABR-pNR2B signaling in a chronic migraine rat model.Frontiers in molecular neuroscience · 2023Article
- In Type 2 Diabetes Mellitus, normalization of hemoglobin A1c accompanies reduced sensitivity to pressure at the sternum.Frontiers in neuroscience · 2023Article
- Sortilin drives hypertension by modulating sphingolipid/ceramide homeostasis and by triggering oxidative stress.The Journal of clinical investigation · 2022Article
- Sortilin Modulates Schwann Cell Signaling and Remak Bundle Regeneration Following Nerve Injury.Frontiers in cellular neuroscience · 2022Article
- Trans-synaptic spreading of alpha-synuclein pathology through sensory afferents leads to sensory nerve degeneration and neuropathic pain.Acta neuropathologica communications · 2021Article
- Latent profile analysis of blood marker phenotypes and their relationships with clinical pain and interference reports in people with acute musculoskeletal trauma.Canadian journal of pain = Revue canadienne de la douleur · 2021Article
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuropathic pain is a major incurable clinical problem resulting from peripheral nerve trauma or disease. A central mechanism is the reduced expression of the potassium chloride cotransporter 2 (KCC2) in dorsal horn neurons induced by brain-derived neurotrophic factor (BDNF), causing neuronal disinhibition within spinal nociceptive pathways. Here, we demonstrate how neurotensin receptor 2 (NTSR2) signaling impairs BDNF-induced spinal KCC2 down-regulation, showing how these two pathways converge to control the abnormal sensory response following peripheral nerve injury. We establish how sortilin regulates this convergence by scavenging neurotensin from binding to NTSR2, thus modulating its inhibitory effect on BDNF-mediated mechanical allodynia. Using sortilin-deficient mice or receptor inhibition by antibodies or a small-molecule antagonist, we lastly demonstrate that we are able to fully block BDNF-induced pain and alleviate injury-induced neuropathic pain, validating sortilin as a clinically relevant target.
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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.