Objectives: African naked mole-rats congenitally lack Substance P (SP) and Calcitonin Gene Related Peptide (CGRP) from their skin and respiratory tract. In other mammals, peripheral release of these peptides at wound sites promotes healing by triggering neutrophil migration, plasma extravasation, local vasodilatation, and immune responses. We hypothesized that the lack of neuropeptides in naked mole-rat skin wound reduce these effects and thus impair wound healing. Methods: Standardized wounds were made just behind the shoulder blades, one on either side of the midline on anesthetized naked mole-rats and laboratory mice with a 3.5 mm biopsy punch. Digital photographs were taken of the wounds each day thereafter to calculate wound area. The rate of wound closure was then compared for naked mole-rats and mice. Wound closure in conjunction with SP treatment was also studied in the mole-rats. During wounding, the right wounds received topical application of saline on the open wound; the left wounds received a topical application of SP. Subsequently, once every day, the right wound received a 50ul injection of saline to the wound from a lateral insertion site; the left wound received SP (100uM) via the same technique Results: The results show the rate of wound closure was significantly slower for naked mole-rats compared to mice. At day 5 post-wounding, the wounds on mice were 80% closed whereas those on the naked mole-rats were less than 20% closed. Also, by Day 5, the SP treated wounds were 23% smaller when compared to the untreated controls. Conclusion: These preliminary results support a role for the neuropeptide SP in wound healing. The naked mole-rat is proving to be a valuable new model to study the mechanisms by which neuropeptides regulate healing. NIH R29DC02850

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