Nervous system plays a crucial role in preserving the integrity of the skin and in promoting the wound healing process. This fact is evidenced by the observation that denervated tissue has an increased propensity for injury with lower threshold of resistance to ischemic conditions and delayed healing. Heat shock proteins (Hsp) play an essential role in protecting the skin against environmental and physical stressors. Basal levels of Hsp’s are expressed signifying the constant exposure to environmental stressors. We, therefore, hypothesized that denervation modifies the expression of Hsp, depriving the skin of a pre-existing protective mechanism against stress. To study the alterations in Hsp expression, we developed a rat epigastric flap model of skin denervation. The flaps were revisited at 1, 3, 7, 14, and 21 days to assess the expression of Hsp70 using Western blot analysis. Expression of Hsp70 was found to be rapidly downregulated within 7 days of denervation. The denervation-induced decline of Hsp70 levels deprives the affected tissue of stress-related protection and hinders the wound repair mechanism. Further studies are being conducted to elucidate the role of subatmospheric pressure such as VAC therapy to neutralize the Hsp70 downregulation in denervated tissue.