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Brivaracetam attenuates pain behaviors in a murine model of neuropathic pain

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 briva...

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Autores principales: Tsymbalyuk, Solomiya, Smith, Madeleine, Gore, Charles, Tsymbalyuk, Orest, Ivanova, Svetlana, Sansur, Charles, Gerzanich, Volodymyr, Simard, J Marc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880061/
https://www.ncbi.nlm.nih.gov/pubmed/31615323
http://dx.doi.org/10.1177/1744806919886503
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author Tsymbalyuk, Solomiya
Smith, Madeleine
Gore, Charles
Tsymbalyuk, Orest
Ivanova, Svetlana
Sansur, Charles
Gerzanich, Volodymyr
Simard, J Marc
author_facet Tsymbalyuk, Solomiya
Smith, Madeleine
Gore, Charles
Tsymbalyuk, Orest
Ivanova, Svetlana
Sansur, Charles
Gerzanich, Volodymyr
Simard, J Marc
author_sort Tsymbalyuk, Solomiya
collection PubMed
description 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.
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spelling pubmed-68800612019-12-05 Brivaracetam attenuates pain behaviors in a murine model of neuropathic pain Tsymbalyuk, Solomiya Smith, Madeleine Gore, Charles Tsymbalyuk, Orest Ivanova, Svetlana Sansur, Charles Gerzanich, Volodymyr Simard, J Marc Mol Pain Research Article 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. SAGE Publications 2019-11-11 /pmc/articles/PMC6880061/ /pubmed/31615323 http://dx.doi.org/10.1177/1744806919886503 Text en © The Author(s) 2019 http://creativecommons.org/licenses/by-nc/4.0/ Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Research Article
Tsymbalyuk, Solomiya
Smith, Madeleine
Gore, Charles
Tsymbalyuk, Orest
Ivanova, Svetlana
Sansur, Charles
Gerzanich, Volodymyr
Simard, J Marc
Brivaracetam attenuates pain behaviors in a murine model of neuropathic pain
title Brivaracetam attenuates pain behaviors in a murine model of neuropathic pain
title_full Brivaracetam attenuates pain behaviors in a murine model of neuropathic pain
title_fullStr Brivaracetam attenuates pain behaviors in a murine model of neuropathic pain
title_full_unstemmed Brivaracetam attenuates pain behaviors in a murine model of neuropathic pain
title_short Brivaracetam attenuates pain behaviors in a murine model of neuropathic pain
title_sort brivaracetam attenuates pain behaviors in a murine model of neuropathic pain
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880061/
https://www.ncbi.nlm.nih.gov/pubmed/31615323
http://dx.doi.org/10.1177/1744806919886503
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