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- Title
Brivaracetam attenuates pain behaviors in a murine model of neuropathic pain.
- Authors
Tsymbalyuk, Solomiya; Smith, Madeleine; Gore, Charles; Tsymbalyuk, Orest; Ivanova, Svetlana; Sansur, Charles; Gerzanich, Volodymyr; Simard, J. Marc
- Abstract
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 10mg/kg) or brivaracetam (10 or 1mg/kg) beginning after surgery and continuing for 21 days, or with therapeutic treatment using brivaracetam (10 or 1mg/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, 10mg/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 1mg/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.
- Subjects
SCIATIC nerve injuries; SYNAPTIC vesicles; TUMOR necrosis factors; SCIATIC nerve; T cells; PERIPHERAL nervous system; ALGOMETRY
- Publication
Molecular Pain, 2019, Vol 15, p1
- ISSN
1744-8069
- Publication type
Article
- DOI
10.1177/1744806919886503