Safety Evaluation of Topically Applied Amitriptyline in Porcine Full-Thickness Wounds

Abstract

The tricyclic antidepressant amitriptyline is frequently used in pain clinics for management of pain. It has also been suggested that topical application of amitriptyline could be useful for the treatment of neuropathic pain. In this report we investigated the effect of amitriptyline on porcine full thickness wounds resembling excised burn wounds. We assessed if daily topical application of amitriptyline into the wound chambers for 10 days impedes wound healing as measured by (1) wound contraction and (2) histopathological findings. Full-thickness wounds measuring 1.5 cm square were created on the dorsum of Yorkshire pigs and were enclosed in polyurethane wound chambers. Amitriptyline was applied daily at various concentrations. Bupivacaine (0.5%) or normal saline were used as controls. Daily wound serum levels were obtained and the level of amitriptyline and nortriptyline obtained. Pictures were taken daily and the wound surface analyzed for contraction. Cross-sectional, full-thickness skin biopsies were obtained at days 2, 8 and 10 and evaluated microscopically for re-epithelialization, inflammation, and necrosis. The high serum level of amitriptyline and nortriptyline did not affect wound healing; re-epithelialization, wound contraction, and inflammation were not significantly different between amitriptyline and control groups. Amitriptyline at the concentrations of 0.0625% and 0.125% applied daily via chambers covering wounds in a full-thickness pig excision model has no overt toxic effect on wound healing as measured by wound contraction and histological assessment.