Inflammation of rat molar pulp and periodontium causes increased calcitonin gene-related peptide and axonal sprouting.
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.
Kimberly
C L
CL
Department of Endodontics, University of Washington, Seattle 98195.
Byers
M R
MR
D000818:Animals; D001369:Axons / Q000503:physiopathology*; D015740:Calcitonin Gene-Related Peptide; D003782:Dental Pulp / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008264:Macrophages / Q000503:physiopathology; D008297:Male; D008963:Molar / Q000294:innervation / Q000378:metabolism*; D009412:Nerve Fibers / Q000378:metabolism / Q000503:physiopathology; D009479:Neuropeptides / Q000276:immunology / Q000378:metabolism*; D010518:Periodontitis / Q000503:physiopathology*; D010519:Periodontium / Q000378:metabolism / Q000473:pathology; D011671:Pulpitis / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains
D009479:Neuropeptides; D015740:Calcitonin Gene-Related Peptide