Abstract

Substance P has a stimulating effect on fibroblast proliferation, collagen organization, and angiogenesis in ruptured and subsequently sutured rat Achilles tendon. This effect is also reflected in the biomechanical properties of the tendon. The aim of this study was to substantiate the effect of exogenous substance P on endogenous substance P, NK-1 receptor, and nerve ingrowth in an in vivo tendon-healing setting. Ninety-six male Sprague-Dawley rats were randomly assigned to one of four groups and injected with saline, substance P (10-6 µmol/kg BW and 10-8 µmol/kg BW) associated with neutral endopeptidase inhibitors, or neutral endopeptidase inhibitors alone into the paratendinous region of the ruptured and subsequently sutured Achilles tendons from the second until the sixth day postoperatively. Substance P, NK-1 receptor, and nerve ingrowth (PGP 9.5) were analysed using immunofluorescence at four different time points : one, two, four and six weeks postoperatively. In all groups substance P was predominantly expressed in the extracellular matrix during the first two weeks, corresponding to fibroblast proliferation, and first disappeared from the saline group in the proliferative phase. In contrast, substance P was not expressed in the blood vessel wall during the first two weeks, when angiogenesis was most pronounced. NK-1 receptor was almost always expressed in the blood vessel wall and in the extracellular matrix during this period and disappeared progressively afterwards. No nerve ingrowth was identified. Exogenously administered substance P in sutured rat Achilles tendon rupture does not stimulate sensory nerve ingrowth, but seems to have a booster effect on endogenous substance P for fibroblast proliferation via autocrine/paracrine stimulation.