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Short-term incubation of gabapentin or pregabalin does not affect chemically induced injury in neuronal cell models in vitro
PURPOSE: Gabapentinoids are currently the mainstay of pharmacological treatments for patients with neuropathic pain. Little is known about the effects of this therapy on the integrity of neuronal networks, especially in patients with an already-damaged nervous system. Since gabapentinoids can worsen...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6016266/ https://www.ncbi.nlm.nih.gov/pubmed/29950890 http://dx.doi.org/10.2147/JPR.S162322 |
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author | Baldewig, Malte Goldbaum, Olaf Richter-Landsberg, Christiane Weyland, Andreas Bantel, Carsten |
author_facet | Baldewig, Malte Goldbaum, Olaf Richter-Landsberg, Christiane Weyland, Andreas Bantel, Carsten |
author_sort | Baldewig, Malte |
collection | PubMed |
description | PURPOSE: Gabapentinoids are currently the mainstay of pharmacological treatments for patients with neuropathic pain. Little is known about the effects of this therapy on the integrity of neuronal networks, especially in patients with an already-damaged nervous system. Since gabapentinoids can worsen cognitive functions and recent studies have shown alterations in the brains of patients with neuropathic pain, it may be possible that these drugs have neurotoxic effects. METHODS: Rat clonal PC12 pheochromocytoma (autonomic) and primary sensory dorsal-root ganglion (DRG) neurons from newborn Wistar rats were employed for this study. To mimic neuronal damage, cells were exposed to cytotoxins using either hydrogen peroxide (H(2)O(2)) or vincristine. RESULTS: No direct cytotoxic effects were observed after incubating PC12 cells for 24 hours with increasing concentrations of gabapentin or pregabalin using MTT cytotoxicity assays. Even a 7-day incubation did not cause cellular damage. Furthermore, in preinjured PC12 and DRG neurons, neither gabapentin nor pregabalin prevented or enhanced the cytotoxic effects of H(2)O(2) or vincristine after incubation for 24 hours and 7 days, respectively. Cell morphology and integrity of the cytoskeleton assessed by employing immunostaining of cytoskeletal proteins (α-tubulin, neurofilament L) remained intact and were not altered by gabapentinoids. CONCLUSION: Based on these results, gabapentinoids are unlikely to be neurotoxic in cultured autonomic (PC12) and sensory DRG cells, even when cells are preinjured. These results are of high clinical relevance, as it seems unlikely that the morphological changes recently observed in the brains of neuropathic pain patients are caused or worsened by gabapentinoids. |
format | Online Article Text |
id | pubmed-6016266 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-60162662018-06-27 Short-term incubation of gabapentin or pregabalin does not affect chemically induced injury in neuronal cell models in vitro Baldewig, Malte Goldbaum, Olaf Richter-Landsberg, Christiane Weyland, Andreas Bantel, Carsten J Pain Res Original Research PURPOSE: Gabapentinoids are currently the mainstay of pharmacological treatments for patients with neuropathic pain. Little is known about the effects of this therapy on the integrity of neuronal networks, especially in patients with an already-damaged nervous system. Since gabapentinoids can worsen cognitive functions and recent studies have shown alterations in the brains of patients with neuropathic pain, it may be possible that these drugs have neurotoxic effects. METHODS: Rat clonal PC12 pheochromocytoma (autonomic) and primary sensory dorsal-root ganglion (DRG) neurons from newborn Wistar rats were employed for this study. To mimic neuronal damage, cells were exposed to cytotoxins using either hydrogen peroxide (H(2)O(2)) or vincristine. RESULTS: No direct cytotoxic effects were observed after incubating PC12 cells for 24 hours with increasing concentrations of gabapentin or pregabalin using MTT cytotoxicity assays. Even a 7-day incubation did not cause cellular damage. Furthermore, in preinjured PC12 and DRG neurons, neither gabapentin nor pregabalin prevented or enhanced the cytotoxic effects of H(2)O(2) or vincristine after incubation for 24 hours and 7 days, respectively. Cell morphology and integrity of the cytoskeleton assessed by employing immunostaining of cytoskeletal proteins (α-tubulin, neurofilament L) remained intact and were not altered by gabapentinoids. CONCLUSION: Based on these results, gabapentinoids are unlikely to be neurotoxic in cultured autonomic (PC12) and sensory DRG cells, even when cells are preinjured. These results are of high clinical relevance, as it seems unlikely that the morphological changes recently observed in the brains of neuropathic pain patients are caused or worsened by gabapentinoids. Dove Medical Press 2018-06-20 /pmc/articles/PMC6016266/ /pubmed/29950890 http://dx.doi.org/10.2147/JPR.S162322 Text en © 2018 Baldewig et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Baldewig, Malte Goldbaum, Olaf Richter-Landsberg, Christiane Weyland, Andreas Bantel, Carsten Short-term incubation of gabapentin or pregabalin does not affect chemically induced injury in neuronal cell models in vitro |
title | Short-term incubation of gabapentin or pregabalin does not affect chemically induced injury in neuronal cell models in vitro |
title_full | Short-term incubation of gabapentin or pregabalin does not affect chemically induced injury in neuronal cell models in vitro |
title_fullStr | Short-term incubation of gabapentin or pregabalin does not affect chemically induced injury in neuronal cell models in vitro |
title_full_unstemmed | Short-term incubation of gabapentin or pregabalin does not affect chemically induced injury in neuronal cell models in vitro |
title_short | Short-term incubation of gabapentin or pregabalin does not affect chemically induced injury in neuronal cell models in vitro |
title_sort | short-term incubation of gabapentin or pregabalin does not affect chemically induced injury in neuronal cell models in vitro |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6016266/ https://www.ncbi.nlm.nih.gov/pubmed/29950890 http://dx.doi.org/10.2147/JPR.S162322 |
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