Brivaracetam attenuates pain behaviors in a murine model of neuropathic pain.
Publication/Presentation Date
1-1-2019
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 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.
Volume
15
First Page
1744806919886503
Last Page
1744806919886503
ISSN
1744-8069
Published In/Presented At
Tsymbalyuk, S., Smith, M., Gore, C., Tsymbalyuk, O., Ivanova, S., Sansur, C., Gerzanich, V., & Simard, J. M. (2019). Brivaracetam attenuates pain behaviors in a murine model of neuropathic pain. Molecular pain, 15, 1744806919886503. https://doi.org/10.1177/1744806919886503
Disciplines
Medicine and Health Sciences
PubMedID
31615323
Department(s)
Fellows and Residents
Document Type
Article