Neuropeptides (Substance P) Localisation in the Peripheral Nervous System and Skin in a Diabetic Rat Model: A Possible Mechanism for Acceleration Wound Healing in Diabetic Rats

Abstract

Background: Diabetes is a metabolic disorder associated with biochemical and neurochemical changes in the tissues. Diabetic neuropathy is attributed to the neurochemical changes and is the underlying cause of the impaired diabetic wound healing. Substance P, a neuropeptide functions as a mediator of local inflammatory responses. Aims: To study the expression of substance P in the peripheral nervous system and in the skin in a diabetic rat model. Additionally, to study the effect of the topical application of substance P on the diabetic wound healing and scarring. Materials and Methods: Streptozotocin-induced diabetic rat model was used. Immunostaining was used to study the expression of substance P, in the peripheral nervous system and in the skin from normal and diabetic unwounded rats. Diabetic wound model was obtained by creating four incisional wounds at the back of the rats. Two wounds were treated by topical application of substance P daily for two weeks and two wounds served as controls. The tissues were harvested two, four and eight weeks postwounding. Macrophage invasion and inducible nitric oxide synthase level (iNOS) were assessed by immunocytochemistry. Postwounding scarring was assessed by Masson Trichrome. Results: Substance P was expressed in the dorsal root ganglia, in the spinal nerves and peripheral dermal nerves both in the diabetic and non-diabetic animals. However, the diabetic rat nerves showed downregulation of substance P and degenerative changes. Diabetic skin showed a significant (P<0.02) downregulation of substance P. Treatment by substance P promoted healing, reduced inflammation and significantly reduced wound macrophage invasion (P<0.007) and iNOS levels (P<0.02). Interestingly, Substance P improved the scar quality and reduced wound width significantly four (P<0.05) and eight (P<0.03) weeks postwounding. Conclusion: This diabetic model was associated with neuropathic changes. Downregulation of substance P in the diabetic nerves could be contributing to the development of diabetic neuropathy and delayed wound healing. Topical application of substance P to the wounds can accelerate the healing, probably through enhancing the vasculature of the skin and relieving diabetic neuropathy. This could provide a new line of treatment for surgical diabetic wounds to achieve early healing with minimal scars.