ArticleNeuropharmacology2017
Bortezomib induces neuropathic pain through protein kinase C-mediated activation of presynaptic NMDA receptors in the spinal cord.
Article in Neuropharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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Who cites it
37 citing papers in PubMed, 52 citations in OpenAlex.
- Tonic GABA and Glycine Inhibition Control Pain Hypersensitivity via Limiting α2δ-1- and mGluR5-Dependent NMDA Receptor Activity at Primary Afferent→Excitatory Neuron Synapses.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- 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
- Bortezomib-induced peripheral neuropathy: from molecular mechanisms to clinical management.Frontiers in pharmacology · 2025Review
- METTL14-mediated m6A epitranscriptomic modification contributes to chemotherapy-induced neuropathic pain by stabilizing GluN2A expression via IGF2BP2.The Journal of clinical investigation · 2024Article
- NMDA Receptors at Primary Afferent-Excitatory Neuron Synapses Differentially Sustain Chemotherapy- and Nerve Trauma-Induced Chronic Pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Duloxetine and Amitriptyline Reduce Neuropathic Pain by Inhibiting Primary Sensory Input to Spinal Dorsal Horn Neurons via α1- and α2-Adrenergic Receptors.ACS chemical neuroscience · 2023Article
- Roles of Phosphorylation of N-Methyl-D-Aspartate Receptor in Chronic Pain.Cellular and molecular neurobiology · 2023Review
- Recent advances in the treatment and prevention of peripheral neuropathy after multiple myeloma treatment.Ibrain · 2023Review
- Electroacupuncture Alleviates Diabetic Neuropathic Pain and Downregulates p-PKC and TRPV1 in Dorsal Root Ganglions and Spinal Cord Dorsal Horn.Evidence-based complementary and alternative medicine : eCAM · 2023Article
- Role of inflammation and oxidative stress in chemotherapy-induced neurotoxicity.Immunologic research · 2022Review
- HDAC2 in Primary Sensory Neurons Constitutively Restrains Chronic Pain by Repressing α2δ-1 Expression and Associated NMDA Receptor Activity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Pregabalin for chemotherapy-induced neuropathy: background and rationale for further study.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2022Review
- Long-Term Treatment with Bortezomib Induces Specific Methylation Changes in Differentiated Neuronal Cells.Cancers · 2022Article
- Protein Kinase C-Mediated Phosphorylation and α2δ-1 Interdependently Regulate NMDA Receptor Trafficking and Activity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- 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
- 6,6'-Dihydroxythiobinupharidine (DTBN) Purified fromMolecules (Basel, Switzerland) · 2021Article
- Article
- Vincristine- and bortezomib-induced neuropathies - from bedside to bench and back.Experimental neurology · 2021Review
- Pathological Mechanisms of Bortezomib-Induced Peripheral Neuropathy.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Chemotherapeutic drugs, including bortezomib, often cause painful peripheral neuropathy, which is a severe dose-limiting adverse effect experienced by many cancer patients. The glutamate N-methyl-d-aspartate receptors (NMDARs) at the spinal cord level are critically involved in the synaptic plasticity associated with neuropathic pain. In this study, we determined whether treatment with bortezomib, a proteasome inhibitor, affects the NMDAR activity of spinal dorsal horn neurons. Systemic treatment with bortezomib in rats did not significantly affect postsynaptic NMDAR currents elicited by puff application of NMDA directly to dorsal horn neurons. Bortezomib treatment markedly increased the baseline frequency of miniature excitatory postsynaptic currents (EPSCs), which was completely normalized by the NMDAR antagonist 2-amino-5-phosphonopentanoic acid (AP5). AP5 also reduced the amplitude of monosynaptic EPSCs evoked by dorsal root stimulation in bortezomib-treated, but not vehicle-treated, rats. Furthermore, inhibition of protein kinase C (PKC) with chelerythrine fully reversed the increased frequency of miniature EPSCs and the amplitude of evoked EPSCs in bortezomib-treated rats. Intrathecal injection of AP5 and chelerythrine both profoundly attenuated mechanical allodynia and hyperalgesia induced by systemic treatment with bortezomib. In addition, treatment with bortezomib induced striking membrane translocation of PKC-βII, PKC-δ, and PKC-ε in the dorsal root ganglion. Our findings indicate that bortezomib treatment potentiates nociceptive input from primary afferent nerves via PKC-mediated tonic activation of presynaptic NMDARs. Targeting presynaptic NMDARs and PKC at the spinal cord level may be an effective strategy for treating chemotherapy-induced neuropathic pain.
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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.