A novel excisional wound pain model for evaluation of analgesics in rats

Abstract

Background: Management of pain from open wounds is a growing unmet healthcare need. However, the models available to study pain from wounds or to develop analgesics for the patients suffering from them have primarily relied on incisional models. Here, we present the first characterized and validated model of open wound pain. Methods: Unilateral full-skin excisional punch biopsy wounds on rat hind paws were evaluated for evoked pain using withdrawal responses to mechanical and thermal stimulation, and spontaneous pain was measured using hind paw weight distribution and guarding behavior. Evaluations were done before wounding (baseline) and 2-96 hours post-wounding. The model was validated by testing the effects of buprenorphine and carprofen. Results: Pain responses to all tests increased within 2 hours post-wounding and were sustained for at least 4 days. Buprenorphine caused a reversal of all four pain responses at 1 and 4 hours post-treatment compared to 0.9% saline (P < 0.001). Carprofen decreased the pain response to thermal stimulation at 1 (P ≤ 0.049) and 4 hours (P < 0.011) post-treatment compared to 0.9% saline, but not to mechanical stimulation. Conclusions: This is the first well-characterized and validated model of pain from open wounds and will allow study of the pathophysiology of pain in open wounds and the development of wound-specific analgesics.