Conditional TNF-α Overexpression in the Tooth and Alveolar Bone Results in Painful Pulpitis and Osteitis

B. E. Hall, L. Zhang, Z. J. Sun, E. Utreras, M. Prochazkova, A. Cho, A. Terse, P. Arany, J. C. Dolan, Brian Schmidt, A. B. Kulkarni

Research output: Contribution to journalArticle

Abstract

Tumor necrosis factor-α (TNF-α) is a proalgesic cytokine that is commonly expressed following tissue injury. TNF-α expression not only promotes inflammation but can also lead to pain hypersensitivity in nociceptors. With the established link between TNF-α and inflammatory pain, we identified its increased expression in the teeth of patients affected with caries and pulpitis. We generated a transgenic mouse model (TNF-αglo) that could be used to conditionally overexpress TNF-α. These mice were bred with a dentin matrix protein 1 (DMP1)-Cre line for overexpression of TNF-α in both the tooth pulp and bone to study oral pain that would result from subsequent development of pulpitis and bone loss. The resulting DMP1/TNF-αglo mice show inflammation in the tooth pulp that resembles pulpitis while also displaying periodontal bone loss. Inflammatory infiltrates and enlarged blood vessels were observed in the tooth pulp. Pulpitis and osteitis affected the nociceptive neurons innervating the orofacial region by causing increased expression of inflammatory cytokines within the trigeminal ganglia. With this new mouse model morphologically mimicking pulpitis and osteitis, we tested it for signs of oral pain with an oral function assay (dolognawmeter). This assay/device records the time required by a mouse to complete a discrete gnawing task. The duration of gnawing required by the DMP1/TNF-αglo mice to complete the task was greater than that for the controls; extended gnaw time in a dolognawmeter indicates reduced orofacial function. With the DMP1/TNF-αglo mice, we have shown that TNF-α expression alone can produce inflammation similar to pulpitis and osteitis and that this mouse model can be used to study dental inflammatory pain.

Original languageEnglish (US)
Pages (from-to)188-195
Number of pages8
JournalJournal of Dental Research
Volume95
Issue number2
DOIs
StatePublished - Feb 1 2016

Fingerprint

Pulpitis
Osteitis
Tooth
Tumor Necrosis Factor-alpha
Bone and Bones
Dentin
Pain
Nociceptors
Inflammation
Proteins
Cytokines
Alveolar Bone Loss
Trigeminal Ganglion
Bone Development
Transgenic Mice
Blood Vessels
Hypersensitivity

Keywords

  • animal model
  • Cdk5
  • cytokine(s)
  • facial pain
  • inflammation
  • toothache

ASJC Scopus subject areas

  • Dentistry(all)

Cite this

Hall, B. E., Zhang, L., Sun, Z. J., Utreras, E., Prochazkova, M., Cho, A., ... Kulkarni, A. B. (2016). Conditional TNF-α Overexpression in the Tooth and Alveolar Bone Results in Painful Pulpitis and Osteitis. Journal of Dental Research, 95(2), 188-195. https://doi.org/10.1177/0022034515612022

Conditional TNF-α Overexpression in the Tooth and Alveolar Bone Results in Painful Pulpitis and Osteitis. / Hall, B. E.; Zhang, L.; Sun, Z. J.; Utreras, E.; Prochazkova, M.; Cho, A.; Terse, A.; Arany, P.; Dolan, J. C.; Schmidt, Brian; Kulkarni, A. B.

In: Journal of Dental Research, Vol. 95, No. 2, 01.02.2016, p. 188-195.

Research output: Contribution to journalArticle

Hall, BE, Zhang, L, Sun, ZJ, Utreras, E, Prochazkova, M, Cho, A, Terse, A, Arany, P, Dolan, JC, Schmidt, B & Kulkarni, AB 2016, 'Conditional TNF-α Overexpression in the Tooth and Alveolar Bone Results in Painful Pulpitis and Osteitis', Journal of Dental Research, vol. 95, no. 2, pp. 188-195. https://doi.org/10.1177/0022034515612022
Hall, B. E. ; Zhang, L. ; Sun, Z. J. ; Utreras, E. ; Prochazkova, M. ; Cho, A. ; Terse, A. ; Arany, P. ; Dolan, J. C. ; Schmidt, Brian ; Kulkarni, A. B. / Conditional TNF-α Overexpression in the Tooth and Alveolar Bone Results in Painful Pulpitis and Osteitis. In: Journal of Dental Research. 2016 ; Vol. 95, No. 2. pp. 188-195.
@article{3e00f63b34cb423689ad35d1285f67b2,
title = "Conditional TNF-α Overexpression in the Tooth and Alveolar Bone Results in Painful Pulpitis and Osteitis",
abstract = "Tumor necrosis factor-α (TNF-α) is a proalgesic cytokine that is commonly expressed following tissue injury. TNF-α expression not only promotes inflammation but can also lead to pain hypersensitivity in nociceptors. With the established link between TNF-α and inflammatory pain, we identified its increased expression in the teeth of patients affected with caries and pulpitis. We generated a transgenic mouse model (TNF-αglo) that could be used to conditionally overexpress TNF-α. These mice were bred with a dentin matrix protein 1 (DMP1)-Cre line for overexpression of TNF-α in both the tooth pulp and bone to study oral pain that would result from subsequent development of pulpitis and bone loss. The resulting DMP1/TNF-αglo mice show inflammation in the tooth pulp that resembles pulpitis while also displaying periodontal bone loss. Inflammatory infiltrates and enlarged blood vessels were observed in the tooth pulp. Pulpitis and osteitis affected the nociceptive neurons innervating the orofacial region by causing increased expression of inflammatory cytokines within the trigeminal ganglia. With this new mouse model morphologically mimicking pulpitis and osteitis, we tested it for signs of oral pain with an oral function assay (dolognawmeter). This assay/device records the time required by a mouse to complete a discrete gnawing task. The duration of gnawing required by the DMP1/TNF-αglo mice to complete the task was greater than that for the controls; extended gnaw time in a dolognawmeter indicates reduced orofacial function. With the DMP1/TNF-αglo mice, we have shown that TNF-α expression alone can produce inflammation similar to pulpitis and osteitis and that this mouse model can be used to study dental inflammatory pain.",
keywords = "animal model, Cdk5, cytokine(s), facial pain, inflammation, toothache",
author = "Hall, {B. E.} and L. Zhang and Sun, {Z. J.} and E. Utreras and M. Prochazkova and A. Cho and A. Terse and P. Arany and Dolan, {J. C.} and Brian Schmidt and Kulkarni, {A. B.}",
year = "2016",
month = "2",
day = "1",
doi = "10.1177/0022034515612022",
language = "English (US)",
volume = "95",
pages = "188--195",
journal = "Journal of Dental Research",
issn = "0022-0345",
publisher = "SAGE Publications Inc.",
number = "2",

}

TY - JOUR

T1 - Conditional TNF-α Overexpression in the Tooth and Alveolar Bone Results in Painful Pulpitis and Osteitis

AU - Hall, B. E.

AU - Zhang, L.

AU - Sun, Z. J.

AU - Utreras, E.

AU - Prochazkova, M.

AU - Cho, A.

AU - Terse, A.

AU - Arany, P.

AU - Dolan, J. C.

AU - Schmidt, Brian

AU - Kulkarni, A. B.

PY - 2016/2/1

Y1 - 2016/2/1

N2 - Tumor necrosis factor-α (TNF-α) is a proalgesic cytokine that is commonly expressed following tissue injury. TNF-α expression not only promotes inflammation but can also lead to pain hypersensitivity in nociceptors. With the established link between TNF-α and inflammatory pain, we identified its increased expression in the teeth of patients affected with caries and pulpitis. We generated a transgenic mouse model (TNF-αglo) that could be used to conditionally overexpress TNF-α. These mice were bred with a dentin matrix protein 1 (DMP1)-Cre line for overexpression of TNF-α in both the tooth pulp and bone to study oral pain that would result from subsequent development of pulpitis and bone loss. The resulting DMP1/TNF-αglo mice show inflammation in the tooth pulp that resembles pulpitis while also displaying periodontal bone loss. Inflammatory infiltrates and enlarged blood vessels were observed in the tooth pulp. Pulpitis and osteitis affected the nociceptive neurons innervating the orofacial region by causing increased expression of inflammatory cytokines within the trigeminal ganglia. With this new mouse model morphologically mimicking pulpitis and osteitis, we tested it for signs of oral pain with an oral function assay (dolognawmeter). This assay/device records the time required by a mouse to complete a discrete gnawing task. The duration of gnawing required by the DMP1/TNF-αglo mice to complete the task was greater than that for the controls; extended gnaw time in a dolognawmeter indicates reduced orofacial function. With the DMP1/TNF-αglo mice, we have shown that TNF-α expression alone can produce inflammation similar to pulpitis and osteitis and that this mouse model can be used to study dental inflammatory pain.

AB - Tumor necrosis factor-α (TNF-α) is a proalgesic cytokine that is commonly expressed following tissue injury. TNF-α expression not only promotes inflammation but can also lead to pain hypersensitivity in nociceptors. With the established link between TNF-α and inflammatory pain, we identified its increased expression in the teeth of patients affected with caries and pulpitis. We generated a transgenic mouse model (TNF-αglo) that could be used to conditionally overexpress TNF-α. These mice were bred with a dentin matrix protein 1 (DMP1)-Cre line for overexpression of TNF-α in both the tooth pulp and bone to study oral pain that would result from subsequent development of pulpitis and bone loss. The resulting DMP1/TNF-αglo mice show inflammation in the tooth pulp that resembles pulpitis while also displaying periodontal bone loss. Inflammatory infiltrates and enlarged blood vessels were observed in the tooth pulp. Pulpitis and osteitis affected the nociceptive neurons innervating the orofacial region by causing increased expression of inflammatory cytokines within the trigeminal ganglia. With this new mouse model morphologically mimicking pulpitis and osteitis, we tested it for signs of oral pain with an oral function assay (dolognawmeter). This assay/device records the time required by a mouse to complete a discrete gnawing task. The duration of gnawing required by the DMP1/TNF-αglo mice to complete the task was greater than that for the controls; extended gnaw time in a dolognawmeter indicates reduced orofacial function. With the DMP1/TNF-αglo mice, we have shown that TNF-α expression alone can produce inflammation similar to pulpitis and osteitis and that this mouse model can be used to study dental inflammatory pain.

KW - animal model

KW - Cdk5

KW - cytokine(s)

KW - facial pain

KW - inflammation

KW - toothache

UR - http://www.scopus.com/inward/record.url?scp=84955239983&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84955239983&partnerID=8YFLogxK

U2 - 10.1177/0022034515612022

DO - 10.1177/0022034515612022

M3 - Article

VL - 95

SP - 188

EP - 195

JO - Journal of Dental Research

JF - Journal of Dental Research

SN - 0022-0345

IS - 2

ER -