Immunohistochemical study of neurochemical markers in gingiva obtained from periodontitis‐affected sites

Abstract

Immunohistochemical methods have been used to study the occurrence of neuronal markers in human gingiva from periodontitis-affected sites. In periodontitis-affected buccal gingiva densely distributed neurofilament (NF)-immunoreactive (IR) fiber bundles were observed in the deeper parts of the propria, while NF-IR single fibers occurred in the superficial propria and occasionally in the buccal epithelium. Periodontitis-affected gingiva obtained from interproximal sites showed only sparsely distributed NF-IR fibers. Single nerve fibers immuno-reactive to the peptides substance P and calcitonin gene-related peptide occurred close to or within the epithelium in both buccal and interproximal gingiva. Around blood vessels neuropeptide Y-, peptide histidine-isoleucine amide- and vasoactive intestinal polypeptide-IR fibers were occasionally observed, while clusters of gamma-melanocyte-stimulating hormone-IR cells were found in the propria, in addition to gamma-melanocyte-stimulating hormone IR nerve fibers. Somatostatin-IR dendritic cells were seen in epithelium and propria of buccal and interproximal gingiva, although a high variability in the number of SOM-IR cells was observed. All neuronal markers studied showed a similar distribution in material obtained from young patients with clinically healthy gingivae, although the number of NF-IR fibers in the propria in these subjects was lower. The results demonstrate that in gingiva obtained from periodontitis-affected sites several different biologically active peptides occur in both nerve fibers and cells. At least some of these substances could possible play a role in the inflammatory process. However, since clinically normal gingiva was shown to contain nerve fibers and cells expressing immunoreactivity to the substances studied, no unique periodontitis-induced expression of the neuronal markers studied was found. Thus, any alteration of these substances during the periodontitis process remains to be elucidated.

Painful Tooth Stimulation Elevates Matrix Metalloproteinase-8 Levels Locally in Human Gingival Crevicular Fluid

“…MMPs are known to be produced by various immunoeffector cells, such as neutrophils, monocytes/macrophages, and fibroblast-like cells (Uitto et al, 2003;Sorsa et al, 2004), often influenced by the pro-inflammatory neuropeptides released from the closely apposed sensory nerves in various tissues (McGillis and Fernandez, 1999), including gingiva (Luthman et al, 1989). Animal studies have shown the existence of branched nerves innervating both intrapulpal and periodontal tissues (Foster and Robinson, 1994).…”

“…Clinically, the pro-inflammatory neuropeptides released by sensory nerves co-ordinate the activities of the immune-effector cells (McGillis and Fernandez, 1999), and may play an important role in the pathogenesis of periodontitis (Luthman et al, 1989). Painful teeth with pulpitis have been shown to be associated with elevated levels in GCF of pro-inflammatory peptides, such as substance P (SP) and neurokinin A (NKA) (Awawdeh et al, 2002a).…”

Neuropeptides and Neurogenic Mechanisms in Oral and Periodontal Inflammation

“…With the recognition that peptidergic neurons extensively innervate the gingivae (Luthman et al, 1988(Luthman et al, , 1989, and the identification of neuropeptides in GCF (Linden et al, 1997(Linden et al, , 2002Lundy et al, 1999Lundy et al, , 2000bHanioka et al, 2000), it is becoming increasingly evident that periodontitis and indeed other orofacial inflammatory disorders may be modulated by imbalances in certain neuropeptides. The distribution of neurochemical markers in tissue obtained from gingivitis-and periodontitis-affected sites led Luthman et al (1989) and Bartold et al (1994) to suggest a possible role for neuropeptides in the pathogenesis of periodontitis. However, in addition to neuropeptides, the intensity and duration of inflammation in periodontal disease are also controlled by a complex regulatory network of inflammatory mediators and immune cells.…”

Distribution of nerve fibers with substance P-orcalcitonin gene-related peptide-like immunoreactivity in ODU plaque-susceptible rats with experimental gingivitis.

“…On the other hand, when Luthman et al (11) examined neurochemical markers in the gingivae from periodontitis-affecte and healthy sites in humans, they found no apparent differences in the number and density of nerve fibers with SP-or CGRP-IR.…”

“…However, the changes of gingival innervation in relation to gingivitis have previously only been described briefly. In human gingivae with periodontitis, Luthman et al (11) found a dense network of neurofilament-immunoreactive fibers. How-Correspondence to Teruo Tanaka, First Department of Oral Anatomy, Kyushu University Faculty of Dentistry, 61, Fukuoka, 812, Japan.…”