Brivaracetam attenuates pain behaviors in a murine model of neuropathic pain
| Autor: | Madeleine C Smith, Charles A. Sansur, Volodymyr Gerzanich, Charles Gore, Svetlana Ivanova, Orest Tsymbalyuk, Solomiya Tsymbalyuk, J. Marc Simard |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine sciatic nerve cuff model levetiracetam microglia Brivaracetam Synaptic vesicle Mice 03 medical and health sciences Cellular and Molecular Neuroscience astrocyte 0302 clinical medicine T lymphocyte medicine Animals mouse neuropathic pain chemistry.chemical_classification Microglia business.industry Mechanism (biology) Immunohistochemistry Pyrrolidinones 3. Good health Mice Inbred C57BL Disease Models Animal 030104 developmental biology Anesthesiology and Pain Medicine medicine.anatomical_structure chemistry Hyperalgesia Neuropathic pain Neuralgia Molecular Medicine Levetiracetam Glycoprotein business Neuroscience 030217 neurology & neurosurgery Research Article medicine.drug Astrocyte |
| Zdroj: | Molecular Pain |
| ISSN: | 1744-8069 |
| DOI: | 10.1177/1744806919886503 |
| Popis: | Background The antiseizure racetams may provide novel molecular insights into neuropathic pain due to their unique mechanism involving synaptic vesicle glycoprotein 2A. Anti-allodynic effects of levetiracetam have been shown in animal models of neuropathic pain. Here, we studied the effect of brivaracetam, which binds to synaptic vesicle glycoprotein 2A with 20-fold greater affinity, and has fewer off-target effects. Methods Mice underwent unilateral sciatic nerve cuffing and were evaluated for mechanical sensitivity using von Frey filaments. Pain behaviors were assessed with prophylactic treatment using levetiracetam (100 or 10 mg/kg) or brivaracetam (10 or 1 mg/kg) beginning after surgery and continuing for 21 days, or with therapeutic treatment using brivaracetam (10 or 1 mg/kg) beginning on day 14, after allodynia was established, and continuing for 28 or 63 days. Spinal cord tissues from the prophylaxis experiment with10 mg/kg brivaracetam were examined for neuroinflammation (Iba1 and tumor necrosis factor), T-lymphocyte (CD3) infiltration, and synaptic vesicle glycoprotein 2A expression. Results When used prophylactically, levetiracetam, 100 mg/kg, and brivaracetam, 10 mg/kg, prevented the development of allodynia, with lower doses of each being less effective. When used therapeutically, brivaracetam extinguished allodynia, requiring 10 days with 10 mg/kg, and six weeks with 1 mg/kg. Brivaracetam was associated with reduced neuroinflammation and reduced T-lymphocyte infiltration in the dorsal horn. After sciatic nerve cuffing, synaptic vesicle glycoprotein 2A expression was identified in neurons, activated astrocytes, microglia/macrophages, and T lymphocytes in the dorsal horn. Conclusion Synaptic vesicle glycoprotein 2A may represent a novel target for neuropathic pain. Brivaracetam may warrant study in humans with neuropathic pain due to peripheral nerve injury. |
| Databáze: | OpenAIRE |
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