Effect of topical neuromodulatory medications on oral and skin keratinocytes

Mustafa Al-Musawi, Justin Durham, John M. Whitworth, Simon J. Stone, Donald R. Nixdorf, Ruth A. Valentine

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Background: Neuromodulatory medications (NMs), 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 NMs on cell lines relevant to the orofacial tissues in vitro as no published studies have examined the effect of these topical NMs. Methods: Cellular viability was measured using alamarBlue®, testing cumulative and specific time point effects of NMs on human skin keratinocytes and oral keratinocytes. Effects of the NMs 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.

Original languageEnglish (US)
Pages (from-to)134-141
Number of pages8
JournalJournal of Oral Pathology and Medicine
Issue number2
StatePublished - Feb 1 2017

Bibliographical note

Funding Information:
The authors thank Bob Tomlinson (Huddersfield Pharmacy Specials Calderdale & Huddersfield NHS Foundation Trust, Huddersfield, UK) for the pharmaceutical advice. This study is funded by the Higher Committee for Education Development in Iraq (HCED) as a part of PhD scholarship in Oral Medicine in the School of Dental Sciences, Newcastle University, United Kingdom. The authors declare no potential conflict of interests with respect to the authorship and/or publication of this article.

Publisher Copyright:
© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd


  • amitriptyline
  • carbamazepine
  • gabapentin
  • neuropathic pain
  • orofacial pain


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