089 Tensile Strength Deficiency in Skin and Wounds Of Substance P Receptor (NK1R) Knockout Mice

Diabetic neuropathy leads to reduced innervation that may in turn diminish the availability of tachykinins such as Substance P (SP). In diabetic mice, exogenous SP has positive effects on wound closure. The role of SP was tested by inactivating the murine SP receptor gene (neurokinin-1 receptor, NK1R). Age-matched, NK1R-/- mice and C57/BL6 control mice were each given 2 full thickness 6 mm excisional wounds on their dorsal surface and creation of two dead space wounds by the insertion of two 1 × 3 mm PVA sponge disks under the skin through a 1.5 cm long ventral midline incision. Digital images for wound closure analysis were collected until day 10 when tissues were harvested for biochemical, histological and tensiometric analysis. There was a striking reduction (2.5 fold, p < 0.05) in the tensile strength of intact, unwounded skin of the NK1R-/- mice, and tensile strength of 10 day incisions was likewise reduced (1.8 fold, p < 0.0126). Wound closure rates were also reduced in the knockout mice, but not to a significant level. Sponge granulation tissue had equivalent protein and DNA content at 10 day post-implantation while collagen content was diminished. Histological examination of excisions, normal skin and sponges showed no readily observable difference in thickness or organization however NK1R-/- mice exhibited visibly less collagen in excisional wounds. The principal dermal effect seen in this gene deletion appears to be the accumulation and organization of connective tissue.  Our preliminary results with a non-diabetic NK1R-/- mouse do not indicate a marked difference in reepithelization, but instead a significant decrease in biomechanics. The parallel diminution of intact skin and wound strength suggests an intrinsic defect in collagen fiber maturation that may be reflected in ultrastructural organization or covalent crosslinking.