Short-term incubation of gabapentin or pregabalin does not affect chemically induced injury in neuronal cell models in vitro
Received 12 January 2018
Accepted for publication 1 April 2018
Published 20 June 2018 Volume 2018:11 Pages 1181—1190
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Andrew Yee
Peer reviewer comments 2
Editor who approved publication: Dr E. Alfonso Romero-Sandoval
Malte Baldewig,1 Olaf Goldbaum,2 Christiane Richter-Landsberg,2 Andreas Weyland,1 Carsten Bantel1
1Department of Anesthesiology, Klinikum Oldenburg, Oldenburg, Germany; 2Molecular Neurobiology, Department of Neuroscience, University of Oldenburg, Oldenburg, Germany
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 (H2O2) 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 H2O2 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.
Keywords: gabapentin, pregabalin, cytotoxicity, cytoskeleton, neuropathic pain
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