Abstract
Pressure ulcers (PUs) or sores are a secondary complication of diabetic neuropathy and traumatic spinal cord injury (SCI). PUs tend to occur in soft tissues located around bony prominences and may heal slowly or not at all. A common mechanism underlying impaired healing of PUs may be dysfunction of the local neurovascular system including deficiency of essential neuropeptides, such as substance P (SP). Previous studies indicate that disturbance in cutaneous sensory innervation leads to a defect in all stages of wound healing, as is the case after SCI. It is hypothesized that nerve fibers enhance wound healing by promoting initial inflammation via the releasing of neuropeptides such as SP. Therefore, we investigated whether exogenous SP improves skin wound healing using in vitro and in vivo models. For in vitro studies, the effects of SP on keratinocyte proliferation and wound closure after a scratch injury were studied under normoxia (pO2 ~21%) or hypoxia (pO2 ~1%) and in presence of normal serum (10% v/v) or low serum (1% v/v) concentrations. Hypoxia and low serum both significantly slowed cell proliferation and wound closure. Under combined low serum and hypoxia, used to mimic the nutrient- and oxygen-poor environment of chronic wounds, SP (10−7 M) significantly enhanced cell proliferation and wound closure rate. For in vivo studies, two full-thickness excisional wounds were created with a 5 mm biopsy punch on the dorsum on either side of the midline of 15-week-old C57BL/6J male and female mice. Immediately, wounds were treated topically with one dose of 0.5 μg SP or PBS vehicle. The data suggest a beneficial role in wound closure and reepithelization, and thus enhanced wound healing, in male and female mice. Taken together, exogenously applied neuropeptide SP enhanced wound healing via cell proliferation and migration in vitro and in vivo. Thus, exogenous SP may be a useful strategy to explore further for treating PUs in SCI and diabetic patients.
Highlights
Pressure ulcers (PUs) or sores are a secondary complication of diabetic neuropathy and traumatic spinal cord injury (SCI)
We investigated the potential of exogenous substance P (SP) to improve wound healIn this study, we investigated the potential of exogenous SP to improve wound ing under unfavorable conditions, such as restricted serum and hypoxia in vitro using healing under unfavorable conditions, such as restricted serum and hypoxia in vitro using keratinocytes, and in full-thickness wounds using 15-week-old male and female mice in keratinocytes, and in full-thickness wounds using 15-week-old male and female mice vivo
In vitro data suggested that hypoxia and low serum concentration significantly duced the rate of cell proliferation and wound healing, whereas exogenous 10−7 M SP sigreduced the rate of cell proliferation and wound healing, whereas exogenous 10−7 M
Summary
Pressure ulcers (PUs) or sores are a secondary complication of diabetic neuropathy and traumatic spinal cord injury (SCI). Hypoxia and low serum both significantly slowed cell proliferation and wound closure. Under combined low serum and hypoxia, used to mimic the nutrient- and oxygen-poor environment of chronic wounds, SP (10−7 M) significantly enhanced cell proliferation and wound closure rate. Exogenously applied neuropeptide SP enhanced wound healing via cell proliferation and migration in vitro and in vivo. PUs are a common but serious complication of spinal cord injury (SCI) and neuropathy due to diabetes and age, and tend to occur in soft tissues (i.e., skin and underlying fat and muscle) located around bony prominences where body weight is concentrated while the patient is sitting or lying [3,4].
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