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Effect of topical neuromodulatory medications on oral and skin keratinocytes
Author(s) -
AlMusawi Mustafa,
Durham Justin,
Whitworth John M.,
Stone Simon J.,
Nixdorf Donald R.,
Valentine Ruth A.
Publication year - 2017
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/jop.12437
Subject(s) - amitriptyline , gabapentin , pharmacology , carbamazepine , viability assay , cytokine , medicine , human skin , in vitro , chemistry , pathology , biology , biochemistry , alternative medicine , psychiatry , epilepsy , genetics
Background Neuromodulatory medications ( NM s), such as amitriptyline, carbamazepine and gabapentin, are used as topical preparations for the management of neuropathic orofacial pain ( NOP ) and have produced promising preliminary results. The aim of this study was to investigate the effects of three aforementioned NM s on cell lines relevant to the orofacial tissues in vitro as no published studies have examined the effect of these topical NM s. Methods Cellular viability was measured using alamarBlue ® , testing cumulative and specific time point effects of NM s on human skin keratinocytes and oral keratinocytes. Effects of the NM s on cell counts were investigated by CCK ‐8 assay. Drug concentrations released from NM orabase pastes after 30‐min incubation were measured by high‐performance liquid chromatography. Using these clinical concentrations, morphological changes and cytokine expression were investigated using scanning electron microscopy ( SEM ) and human inflammatory antibody array ( AAH ), respectively. Results Cumulative and specific time point viability and cell count methods revealed that amitriptyline caused a significant decrease in cellular viability and counts in both cell lines. Carbamazepine also had significant effects after long‐term exposure and at higher concentrations, whilst gabapentin had little demonstrable effect. SEM confirmed the cytotoxicity of amitriptyline, whilst AAH revealed no significant changes in cytokine expression following amitriptyline, carbamazepine or gabapentin exposure compared with control. Conclusions The results raise concerns about the safety of topical amitriptyline as it was cytotoxic to skin and oral keratinocytes in both exposure times and concentrations, whilst carbamazepine was cytotoxic only at high concentrations and after longer exposure times and gabapentin had no demonstrable effects.