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Forty-four primary canine teeth, classified into 3 defined PRR stages (early, middle, and advanced) were fixed and demineralized. Longitudinal cryosections of each tooth were stained for immunohistochemical and quantitative analysis of dental pulp nerve fibers and associated components with confocal and electron microscopy. During PRR, axonal degeneration was prominent and progressive in a Wallerian-like scheme, comprising nerve fiber bundles and nerve endings within the coronal and root pulp. Neurofilament fragmentation increased significantly during PRR progression and was accompanied by myelin degradation and a progressive loss of myelinated axons. Myelin sheath degradation involved activation of autophagic activity by Schwann cells to remove myelin debris. These cells expressed a sequence of responses comprising dedifferentiation, proliferative activity, GAP-43 overexpression, and B\u00fcngner band formation. During the advanced PRR stage, increased immune cell recruitment within the dental pulp and major histocompatibility complex (MHC) class II upregulation by Schwann cells characterized an inflammatory condition associated with the denervation process in preexfoliative primary teeth. The ensuing loss of dental pulp axons is likely to be responsible for the progressive reduction of sensory function of the dental pulp during preexfoliative stages.<\/jats:p>","DOI":"10.1177\/0022034515593055","type":"journal-article","created":{"date-parts":[[2015,7,6]],"date-time":"2015-07-06T22:49:52Z","timestamp":1436222992000},"page":"1446-1453","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":23,"title":["Axonal Degeneration in Dental Pulp Precedes Human Primary Teeth Exfoliation"],"prefix":"10.1177","volume":"94","author":[{"given":"K.","family":"Suzuki","sequence":"first","affiliation":[{"name":"Cl\u00ednica de Odontolog\u00eda Pedi\u00e1trica y del Adolescente, Universidad de Valpara\u00edso, Valpara\u00edso, Chile"},{"name":"Facultad de Odontolog\u00eda, Universidad de Valpara\u00edso, Valpara\u00edso, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Lovera","sequence":"additional","affiliation":[{"name":"Facultad de Odontolog\u00eda, Universidad de Valpara\u00edso, Valpara\u00edso, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"O.","family":"Schmachtenberg","sequence":"additional","affiliation":[{"name":"Centro Interdisciplinario de Neurociencia de Valpara\u00edso (CINV), Universidad de Valpara\u00edso, Valpara\u00edso, Chile"},{"name":"Facultad de Ciencias, Universidad de Valpara\u00edso, Valpara\u00edso, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Couve","sequence":"additional","affiliation":[{"name":"Centro Interdisciplinario de Neurociencia de Valpara\u00edso (CINV), Universidad de Valpara\u00edso, Valpara\u00edso, Chile"},{"name":"Facultad de Ciencias, Universidad de Valpara\u00edso, Valpara\u00edso, Chile"},{"name":"Instituto de Biolog\u00eda, Laboratorio de Microscop\u00eda Electr\u00f3nica, Universidad de Valpara\u00edso, Valpara\u00edso, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2015,7,6]]},"reference":[{"key":"bibr1-0022034515593055","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2012.05.005"},{"key":"bibr2-0022034515593055","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-9969(03)00173-0"},{"key":"bibr3-0022034515593055","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.06.021"},{"key":"bibr4-0022034515593055","doi-asserted-by":"publisher","DOI":"10.1016\/j.tripleo.2006.11.047"},{"key":"bibr5-0022034515593055","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(86)91334-X"},{"key":"bibr6-0022034515593055","doi-asserted-by":"publisher","DOI":"10.1177\/10454411990100010101"},{"key":"bibr7-0022034515593055","doi-asserted-by":"publisher","DOI":"10.1002\/jemt.10291"},{"key":"bibr8-0022034515593055","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1788"},{"key":"bibr9-0022034515593055","doi-asserted-by":"publisher","DOI":"10.1177\/0022034514539507"},{"key":"bibr10-0022034515593055","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(02)00291-9"},{"key":"bibr11-0022034515593055","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2013.04.010"},{"key":"bibr12-0022034515593055","unstructured":"Fried K, Gibbs JL. 2014. 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