ArticleJournal of neuroinflammation2018
Ammoxetine attenuates diabetic neuropathic pain through inhibiting microglial activation and neuroinflammation in the spinal cord.
Article in Journal of neuroinflammation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 91 citations in OpenAlex.
- Depressive disorders: systematic review of approved psychiatric medications (2009-April 2025) and pipeline phase 3 medications.BMC psychiatry · 2025Pooled it
- Glial Triad in Diabetic Neuropathy: Central Players in Neuropathic Pain Pathogenesis and Disease-Modifying Therapeutic Avenues.Biomedicines · 2026Review
- The Small Molecule Compound Eupalinolide B Alleviates Neuropathic Pain by Regulating the USP7/Keap1/Nrf2 Pathway.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- Role of astrocytes in diabetic neuropathy: Review of their involvement in disease mechanisms.World journal of diabetes · 2025Review
- Cytokine Signaling in Diabetic Neuropathy: A Key Player in Peripheral Nerve Damage.Biomedicines · 2025Review
- Distinct Roles of Astrocytes and GABAergic Neurons in the Paraventricular Thalamic Nucleus in Modulating Diabetic Neuropathic Pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Spinal neuron-glial crosstalk and ion channel dysregulation in diabetic neuropathic pain.Frontiers in immunology · 2025Review
- Update on Biomarkers of Chronic Inflammatory Processes Underlying Diabetic Neuropathy.International journal of molecular sciences · 2024Review
- The Potentiality of Natural Products and Herbal Medicine as Novel Medications for Parkinson's Disease: A Promising Therapeutic Approach.International journal of molecular sciences · 2024Review
- Novel drugs affecting diabetic peripheral neuropathy.Iranian journal of basic medical sciences · 2024Review
- Article
- Diabetic Neuropathic Pain and Circadian Rhythm: A Future Direction Worthy of Study.Journal of pain research · 2024Review
- Neuroprotective Effects of Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors (Gliflozins) on Diabetes-Induced Neurodegeneration and Neurotoxicity: A Graphical Review.International journal of preventive medicine · 2024Review
- Role of microglia in diabetic neuropathic pain.Frontiers in cell and developmental biology · 2024Review
- [Metformin alleviates pathologic pain in mice with radiation dermatitis by inhibiting p38MAPK/NF-κB signaling pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- Diabetic Neuropathic Pain and Serotonin: What Is New in the Last 15 Years?Biomedicines · 2023Review
- Neuronal-Hematopoietic Cell Fusion in Diabetic Neuropathy.Stem cells translational medicine · 2023Article
- Suppression of neuronal apoptosis and glial activation with modulation of Nrf2/HO-1 and NF-kB signaling by curcumin in streptozotocin-induced diabetic spinal cord central neuropathy.Frontiers in neuroanatomy · 2023Article
- DKK3 ameliorates neuropathic pain via inhibiting ASK-1/JNK/p-38-mediated microglia polarization and neuroinflammation.Journal of neuroinflammation · 2022Article
- Upregulation of TLR9 may contribute to activation of microglia and painful diabetic neuropathy via the p38 MAPK pathway in rats.Histology and histopathology · 2022Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundDiabetic neuropathic pain (DNP) is a common and distressing complication in patients with diabetes, and the underlying mechanism remains unclear. Tricyclic antidepressants (TCAs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) are recommended as first-line drugs for DNP. Ammoxetine is a novel and potent SNRI that exhibited a strong analgesic effect on models of neuropathic pain, fibromyalgia-related pain, and inflammatory pain in our primary study. The present study was undertaken to investigate the chronic treatment properties of ammoxetine on DNP and the underlying mechanisms for its effects.
methodsThe rat model of DNP was established by a single streptozocin (STZ) injection (60 mg/kg). Two weeks after STZ injection, the DNP rats were treated with ammoxetine (2.5, 5, and 10 mg/kg/day) for 4 weeks. The mechanical allodynia and locomotor activity were assayed to evaluate the therapeutic effect of ammoxetine. In mechanism study, the activation of microglia, astrocytes, the protein levels of pro-inflammatory cytokines, the mitogen-activated protein kinases (MAPK), and NF-κB were evaluated. Also, microglia culture was used to assess the direct effects of ammoxetine on microglial activation and the signal transduction mechanism.
resultsTreatment with ammoxetine for 4 weeks significantly relieved the mechanical allodynia and ameliorated depressive-like behavior in DNP rats. In addition, DNP rats displayed increased activation of microglia in the spinal cord, but not astrocytes. Ammoxetine reduced the microglial activation, accumulation of pro-inflammatory cytokines, and activation of p38 and c-Jun N-terminal kinase (JNK) in the spinal cord of DNP rats. Furthermore, ammoxetine displayed anti-inflammatory effects upon challenge with LPS in BV-2 microglia cells.
conclusionOur results suggest that ammoxetine may be an effective treatment for relieving DNP symptoms. Moreover, a reduction in microglial activation and pro-inflammatory release by inhibiting the p-p38 and p-JNK pathways is involved in the mechanism.
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