Distribution of substance P and neurokinin-1 receptors in the peri-implant epithelium around titanium dental implants in rats

Abstract

We examined the distribution of substance P and neurokinin-1 (NK1) receptors and substance-P-containing nerve fibers in the peri-implant mucosa around titanium dental implants in rats. Immunohistochemistry and immunocytochemistry revealed that substance-P-immunoreactive nerve fibers abundantly innervated the peri-implant epithelium (PIE) compared with other epithelia of the peri-implant mucosa. NK1 receptor mRNA and protein expression in the peri-implant mucosa were confirmed by reverse transcription with the polymerase chain reaction and immunoblotting. Immunoelectron microscopy revealed that NK1 receptor immunoreactivity was preferentially localized in peri-implant epithelial cells. NK1-receptor-positive products were found on the plasma membrane and in vesicles and granules in PIE cells. Neutrophils and intraepithelial nerve axons in the PIE were positive for the NK1 receptor. NK1 receptor immunoreactivity was also detected in endothelial cells, fibroblasts, and nerve fibers in the connective tissue beneath the PIE. These findings suggest that peri-implant tissue receives sensory information through regenerated nerves expressing substance P and the NK1 receptor. In the peri-implant mucosa, the substance P/NK1 receptor system may play a role in pain transmission, the endocytosis of neutrophils, the extravasation of crevicular fluid, and the migration of macrophages and neutrophils in response to neurogenic inflammation, as in healthy gingiva.

False positive reactivity of a substance P-antibody in the ectodermal/epithelial plug of the nose, ear, eye and perineum of the human and mouse fetuses

“…S100 protein. Similar findings on the SP expression of non-neuronal cells have been reported in cultured corneal cells (Watanabe et al 2002) and around dental implants (Yamaza et al 2009), but the present subjects were normal fetal morphology. Moreover, although the examined sites and stages were limited, this antibody reacted with specific events in the mouse head development: the palate fusion and dental germ.…”

Biological Sealing and Defense Mechanisms in Peri-Implant Mucosa of Dental Implants

“…This chapter reviews the morphological and functional features of the soft tissue surrounding dental implants, with emphasis on the epithelial interface between the implant and the peri-implant mucosa. The evidence is based on recent animal studies, especially our investigations using a unique oral implant rat model (Ikeda et al, 2000, 202;Atsuta et al, 2005aAtsuta et al, , 2005bYamaza et al, 2009). This in vivo model uses a 4-week implantation system, immediately after tooth extraction (maxillary first molar).…”

“…Blood vessels, especially post-capillary venules, mostly occur under the sub-PIE connective tissue, compared to other sub-periimplant epithelial tissue (Figure 3b). and invade into the PIE (Ikeda et al, 2000;Yamaza et al, 2009) (Figure 5c). These ultrastructural characteristics support the idea that the PIE acts as a pathway not only for foreign molecules penetrating into the sub-epithelial connective tissue of the peri-implant mucosa (Ikeda et al, 2002), but also for the flow of peri-implant cervicular fluid from the sup-epithelial tissue (Eley et al, 1991).…”

“…The PIE cells also contain tonofilaments (Figure 5a) that associate with desmosomes and hemidesmosomes (Schroeder, 1986). Many lysosomal vesicular and vacuolar structures are located in the cytoplasm (Ikeda et al, 2000;Yamaza et al, 2009) (Figures 5a and 10c). …”

“…The sensory nerve fibers contain the neuropeptides, calcitonin gene-related peptide (Byers et al, 1987;Nagata et al, 1992Nagata et al, , 1994 and substance P (Nagata et al, , 1994Tanaka et al, 1996;Kido et al, 1999), and terminate close to endothelial cells, neutrophils, and junctional epithelial cells Tanaka et al, 1996). The peri-implant mucosa is also supplied with sensory nerves containing calcitonin generelated peptide (Fujii et al, 2003) and substance P (Yamaza et al, 2009) (Figure 7a). The innervation of the PIE is denser than in other parts of the epithelium (peri-implant sulcular epithelium and oral epithelium) (Figure 7b).…”