TNFα in the Trigeminal Nociceptive System Is Critical for Temporomandibular Joint Pain

Qian Bai, Sufang Liu, Hui Shu, Yuanyuan Tang, Sanjeeth George, Tieli Dong, Brian Schmidt, Feng Tao

Research output: Contribution to journalArticle

Abstract

Previous studies have shown that tumor necrosis factor alpha (TNFα) is significantly increased in complete Freund’s adjuvant (CFA)-treated temporomandibular joint (TMJ) tissues. However, it is unclear whether TNFα in the trigeminal nociceptive system contributes to the development of TMJ pain. In the present study, we investigated the role of TNFα in trigeminal ganglia (TG) and spinal trigeminal nucleus caudalis (Sp5C) in CFA-induced inflammatory TMJ pain. Intra-TMJ injection of CFA (10 μl, 5 mg/ml) induced inflammatory pain in the trigeminal nerve V2- and V3-innervated skin areas of WT mice, which was present on day 1 after CFA and persisted for at least 10 days. TNFα in both TG and Sp5C of WT mice was upregulated after CFA injection. The CFA-induced TMJ pain was significantly inhibited in TNFα KO mice. The immunofluorescence staining showed that intra-TMJ CFA injection not only enhanced co-localization of TNFα with Iba1 (a marker for microglia) in both TG and Sp5C but also markedly increased the expression of TNFα in the Sp5C neurons. By the methylated DNA immunoprecipitation assay, we also found that DNA methylation at the TNF gene promoter region in the TG was dramatically diminished after CFA injection, indicating that epigenetic regulation may be involved in the CFA-enhanced TNFα expression in our model. Our results suggest that TNFα in the trigeminal nociceptive system plays a critical role in CFA-induced inflammatory TMJ pain.

Original languageEnglish (US)
Pages (from-to)1-14
Number of pages14
JournalMolecular Neurobiology
DOIs
StateAccepted/In press - Apr 25 2018

Fingerprint

Freund's Adjuvant
Temporomandibular Joint
Arthralgia
Tumor Necrosis Factor-alpha
Trigeminal Ganglion
Injections
Spinal Trigeminal Nucleus
Trigeminal Nerve
Microglia
DNA Methylation
Immunoprecipitation
Genetic Promoter Regions
Epigenomics
Fluorescent Antibody Technique
Staining and Labeling
Neurons
Pain
Skin

Keywords

  • Inflammatory pain
  • Spinal trigeminal nucleus caudalis
  • Temporomandibular joint
  • Trigeminal ganglia
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Bai, Q., Liu, S., Shu, H., Tang, Y., George, S., Dong, T., ... Tao, F. (Accepted/In press). TNFα in the Trigeminal Nociceptive System Is Critical for Temporomandibular Joint Pain. Molecular Neurobiology, 1-14. https://doi.org/10.1007/s12035-018-1076-y

TNFα in the Trigeminal Nociceptive System Is Critical for Temporomandibular Joint Pain. / Bai, Qian; Liu, Sufang; Shu, Hui; Tang, Yuanyuan; George, Sanjeeth; Dong, Tieli; Schmidt, Brian; Tao, Feng.

In: Molecular Neurobiology, 25.04.2018, p. 1-14.

Research output: Contribution to journalArticle

Bai, Qian ; Liu, Sufang ; Shu, Hui ; Tang, Yuanyuan ; George, Sanjeeth ; Dong, Tieli ; Schmidt, Brian ; Tao, Feng. / TNFα in the Trigeminal Nociceptive System Is Critical for Temporomandibular Joint Pain. In: Molecular Neurobiology. 2018 ; pp. 1-14.
@article{e60d7b3d29bb4850b66cec0d91259269,
title = "TNFα in the Trigeminal Nociceptive System Is Critical for Temporomandibular Joint Pain",
abstract = "Previous studies have shown that tumor necrosis factor alpha (TNFα) is significantly increased in complete Freund’s adjuvant (CFA)-treated temporomandibular joint (TMJ) tissues. However, it is unclear whether TNFα in the trigeminal nociceptive system contributes to the development of TMJ pain. In the present study, we investigated the role of TNFα in trigeminal ganglia (TG) and spinal trigeminal nucleus caudalis (Sp5C) in CFA-induced inflammatory TMJ pain. Intra-TMJ injection of CFA (10 μl, 5 mg/ml) induced inflammatory pain in the trigeminal nerve V2- and V3-innervated skin areas of WT mice, which was present on day 1 after CFA and persisted for at least 10 days. TNFα in both TG and Sp5C of WT mice was upregulated after CFA injection. The CFA-induced TMJ pain was significantly inhibited in TNFα KO mice. The immunofluorescence staining showed that intra-TMJ CFA injection not only enhanced co-localization of TNFα with Iba1 (a marker for microglia) in both TG and Sp5C but also markedly increased the expression of TNFα in the Sp5C neurons. By the methylated DNA immunoprecipitation assay, we also found that DNA methylation at the TNF gene promoter region in the TG was dramatically diminished after CFA injection, indicating that epigenetic regulation may be involved in the CFA-enhanced TNFα expression in our model. Our results suggest that TNFα in the trigeminal nociceptive system plays a critical role in CFA-induced inflammatory TMJ pain.",
keywords = "Inflammatory pain, Spinal trigeminal nucleus caudalis, Temporomandibular joint, Trigeminal ganglia, Tumor necrosis factor-α",
author = "Qian Bai and Sufang Liu and Hui Shu and Yuanyuan Tang and Sanjeeth George and Tieli Dong and Brian Schmidt and Feng Tao",
year = "2018",
month = "4",
day = "25",
doi = "10.1007/s12035-018-1076-y",
language = "English (US)",
pages = "1--14",
journal = "Molecular Neurobiology",
issn = "0893-7648",
publisher = "Humana Press",

}

TY - JOUR

T1 - TNFα in the Trigeminal Nociceptive System Is Critical for Temporomandibular Joint Pain

AU - Bai, Qian

AU - Liu, Sufang

AU - Shu, Hui

AU - Tang, Yuanyuan

AU - George, Sanjeeth

AU - Dong, Tieli

AU - Schmidt, Brian

AU - Tao, Feng

PY - 2018/4/25

Y1 - 2018/4/25

N2 - Previous studies have shown that tumor necrosis factor alpha (TNFα) is significantly increased in complete Freund’s adjuvant (CFA)-treated temporomandibular joint (TMJ) tissues. However, it is unclear whether TNFα in the trigeminal nociceptive system contributes to the development of TMJ pain. In the present study, we investigated the role of TNFα in trigeminal ganglia (TG) and spinal trigeminal nucleus caudalis (Sp5C) in CFA-induced inflammatory TMJ pain. Intra-TMJ injection of CFA (10 μl, 5 mg/ml) induced inflammatory pain in the trigeminal nerve V2- and V3-innervated skin areas of WT mice, which was present on day 1 after CFA and persisted for at least 10 days. TNFα in both TG and Sp5C of WT mice was upregulated after CFA injection. The CFA-induced TMJ pain was significantly inhibited in TNFα KO mice. The immunofluorescence staining showed that intra-TMJ CFA injection not only enhanced co-localization of TNFα with Iba1 (a marker for microglia) in both TG and Sp5C but also markedly increased the expression of TNFα in the Sp5C neurons. By the methylated DNA immunoprecipitation assay, we also found that DNA methylation at the TNF gene promoter region in the TG was dramatically diminished after CFA injection, indicating that epigenetic regulation may be involved in the CFA-enhanced TNFα expression in our model. Our results suggest that TNFα in the trigeminal nociceptive system plays a critical role in CFA-induced inflammatory TMJ pain.

AB - Previous studies have shown that tumor necrosis factor alpha (TNFα) is significantly increased in complete Freund’s adjuvant (CFA)-treated temporomandibular joint (TMJ) tissues. However, it is unclear whether TNFα in the trigeminal nociceptive system contributes to the development of TMJ pain. In the present study, we investigated the role of TNFα in trigeminal ganglia (TG) and spinal trigeminal nucleus caudalis (Sp5C) in CFA-induced inflammatory TMJ pain. Intra-TMJ injection of CFA (10 μl, 5 mg/ml) induced inflammatory pain in the trigeminal nerve V2- and V3-innervated skin areas of WT mice, which was present on day 1 after CFA and persisted for at least 10 days. TNFα in both TG and Sp5C of WT mice was upregulated after CFA injection. The CFA-induced TMJ pain was significantly inhibited in TNFα KO mice. The immunofluorescence staining showed that intra-TMJ CFA injection not only enhanced co-localization of TNFα with Iba1 (a marker for microglia) in both TG and Sp5C but also markedly increased the expression of TNFα in the Sp5C neurons. By the methylated DNA immunoprecipitation assay, we also found that DNA methylation at the TNF gene promoter region in the TG was dramatically diminished after CFA injection, indicating that epigenetic regulation may be involved in the CFA-enhanced TNFα expression in our model. Our results suggest that TNFα in the trigeminal nociceptive system plays a critical role in CFA-induced inflammatory TMJ pain.

KW - Inflammatory pain

KW - Spinal trigeminal nucleus caudalis

KW - Temporomandibular joint

KW - Trigeminal ganglia

KW - Tumor necrosis factor-α

UR - http://www.scopus.com/inward/record.url?scp=85046019995&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85046019995&partnerID=8YFLogxK

U2 - 10.1007/s12035-018-1076-y

DO - 10.1007/s12035-018-1076-y

M3 - Article

SP - 1

EP - 14

JO - Molecular Neurobiology

JF - Molecular Neurobiology

SN - 0893-7648

ER -