Amitriptyline as a Novel Long Lasting Local Anesthetic and Anti-Inflammatory Agent for Treatment of Full-Thickness Wounds

Abstract

Satisfactory management of acute burn pain remains an unresolved task. Local anesthetics are toxic in large amounts and duration of their action is limited. Morphine is therefore the mainstay of the burn victims' pain management. High doses of narcotics (non-selective pain medications) contribute to numerous complications such as respiratory, gastrointestinal or circulatory. Often the pain control is the only indication for intubation, or contraindication for extubation. Burn patients require a long-term treatment, and additional problems may arise from narcotic dependence. Amitriptyline is a tricyclic antidepressant with significant effect locally through yet to be described mechanism of action. It has been shown to induce local anesthesia for up to 2 weeks following subcutaneous administration without obvious local or systemic toxicity. Additionally, amitriptyline increases the level of anti-inflammatory molecules (IL-10), and decreases the levels of pro-inflammatory molecules (IL-1β, TNFα). In this study we investigated the local toxicity of amitriptyline and effect on wound healing in porcine model. A total of 16 full-thickness excisional wounds were created on the dorsum of 3 months old Yorkshire pig. The wounds were infiltrated with a total of 3ml of amitriptyline with concentrations of 0.5% (3 wounds), 0.75% (3 wounds) and 2.5% (3 wounds). The amitriptyline concentrations were selected based on prior experience on nerve block and subcutaneous block in rats as well as from human studies on nerve block. As a control we used 0.25% bupivacaine (2 wounds) and saline (2 wounds). The wounds were biopsied and evaluated by a dermatopathologist for any evidence of toxicity.