Inflammation of rat molar pulp and periodontium causes increased calcitonin gene‐related peptide and axonal sprouting

Abstract

We have studied the response of nerve fibers containing calcitonin gene-related peptide immunoreactivity (CGRP-IR) to inflammation using a rate dental experimental system. Inflammation was induced by drilling tooth cusps to create pulpal exposures; the induced pulpitis and subsequent periapical lesions were studied 1-35 days later using standard CGRP immunohistochemistry and the avidin-biotin peroxidase method. The injury and resulting inflammation caused a disruption of CGRP-IR nerve fiber location and arborization that varied depending on whether the initial injury was limited to the pulp tip or extended throughout the pulp horn. At shorter survival periods (24 hr, 3 days) nerve fibers were either decreased or bundled into the center of the pulp with sprouting along the wound border. At 6 days necrosis and acute inflammation had advanced to varying degrees, and CGRP-IR fibers were extensively sprouted in the surviving pulp; the pulp also stained specifically for CGRP within 1-2 mm of the inflamed tissue at 6 days. At 35 days, we found total pulp necrosis in most teeth and the development of periapical bone loss, granulomatous tissue, and periapical abscesses. There was also an extensive increase in CGRP-IR nerve fibers in the tissues surrounding sites of severe periodontal inflammation and necrosis. In some cases, macrophage-like cells staining specifically for CGRP were near the abscesses. The results show important interactions between peptidergic nerve fibers and inflammatory cells, and are discussed in terms of the role of nerve fibers containing CGRP in neurogenic inflammation, mechanisms for intensification of CGRP immunoreactivity in affected fibers or neighboring cells, and implications for chronic inflammatory conditions, dental pain, and anesthesia.

Immunoelectron Microscopic Observation of Calcitonin Gene-Related Peptide(CGRP)-positive Nerves in the Dental Pulp of Rat Molars.

“…Distribution of CGRP-immunoreactive nerve fibers in the dental pulp of rat molars coincided with that reported in previous literature (HosHINO et al, 1987;KIMBERLY and BYERS, 1988;KHAYAT et al, 1988). CGRPimmunoteactive nerve fibers, beaded in profile, entered the dental pulp through the apical foramen.…”

Immunoelectron Microscopic Study of CGRP-Immunoreactive Nerve Terminals in Wound Healing and Dentin Bridge Formation after Pulpotomy in Rat Molar

“…Sensory nerve fibers play a possible role both in regulating the differentiation and proliferation of pulpal cells during the inflammation or healing processes following pulpal exposure or cavity preparation [1,3,9,10,13]. Sensory denervation showed a significant reduction in dentin formation at the pulp horn [8].…”

“…The immunohistochemical identification of nerve fibers has been used to evaluate sensory neuropeptides such as CGRP and substance P [5,8,10,13]. Although the pulpal nerve fibers that contain CGRP have recently been shown to play an important role in the pulp response to inflammation and wound healing [10,14], no studies have yet elucidated the relationship between the CGRP-IR nerve terminals and the differentiation of undifferentiated mesenchymal cells into fibroblast-like cells and odontoblasts during the healing process after a pulpotomy with the use of immunoelectron microscopy.…”

“…Although the pulpal nerve fibers that contain CGRP have recently been shown to play an important role in the pulp response to inflammation and wound healing [10,14], no studies have yet elucidated the relationship between the CGRP-IR nerve terminals and the differentiation of undifferentiated mesenchymal cells into fibroblast-like cells and odontoblasts during the healing process after a pulpotomy with the use of immunoelectron microscopy. Our preceding paper described the relationship between CGRP-IR innervation and dentin bridge formation following a pulpotomy in the rat molar based on light microscopic immunohistochemistry [17].…”

Distribution of Peripherin Immunoreactive Axons in Rat Molar Pulp

“…3C and 3F-III)와 신경얼기 ( CGRP는 주로 염증성 동통전달에 관련된 신경전달물 질로서, 펩타이드성 민말이집 혹은 작은 말이집 축삭 표지자로 많이 사용되며 [8,9], 혈관확장, 대식세포와 백 혈구 조절 등의 면역작용에 관여한다고 알려져 있다 [18,19]. 또한 치수에 염증이 발생하였을 때 CGRP 면역 양성 축삭들은 염증부위에서 급격히 그 수가 증가하는 sprouting 현상을 보임으로써 치수염에 따른 염증성 통 각과민에 깊이 관여하는 물질로 알려져 있으며 [20][21][22], 이러한 sprouting이 이차상아질형성과 재생과정에 관여 할 것이라는 주장도 제시된 바 있다 [22,23] …”