ArticleJournal of neuroinflammation2013
Toll-like receptor 4 signaling in trigeminal ganglion neurons contributes tongue-referred pain associated with tooth pulp inflammation.
Article in Journal of neuroinflammation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Genetic variants at theRMD open · 2021Pooled it
- Trigemino-gustatory interactions: a randomized controlled clinical trial assessing the effects of selective anesthesia of dental afferents on taste thresholds.Clinical oral investigations · 2018Trial
- The Role of Stress in Burning Mouth Syndrome Triggered by Dental Treatments: A Two-Step Hypothesis.Journal of oral rehabilitation · 2025Article
- From sensation to regulation: the diverse functions of peripheral sensory nervous system.Frontiers in immunology · 2025Review
- Sensory neuronal control of skin barrier immunity.Trends in immunology · 2024Review
- Lipopolysaccharide-induced Trigeminal Ganglion Nerve Fiber Damage is Associated with Autophagy Inhibition.Current medical science · 2023Article
- Upregulation of Toll-like Receptor 2 in Dental Primary Afferents Following Pulp Injury.Experimental neurobiology · 2021Article
- Role of macrophage-mediated Toll-like receptor 4-interleukin-1R signaling in ectopic tongue pain associated with tooth pulp inflammation.Journal of neuroinflammation · 2020Article
- Evoked and spontaneous pain assessment during tooth pulp injury.Scientific reports · 2020Article
- Toll-Like Receptor 4 in the Rat Caudal Medulla Mediates Tooth Pulp Inflammatory Pain.Frontiers in neuroscience · 2020Article
- The Neuroimmune Axis in Skin Sensation, Inflammation, and Immunity.Journal of immunology (Baltimore, Md. : 1950) · 2019Review
- Alterations in the gustatory papillae after anterior bite plate insertion in growing rats.Journal of orthodontic science · 2019Article
- Peripheral and Central Mechanisms of Persistent Orofacial Pain.Frontiers in neuroscience · 2019Review
- Neurogenic inflammation and its role in migraine.Seminars in immunopathology · 2018Review
- Activation of trigeminal ganglion satellite glial cells in CFA-induced tooth pulp pain in rats.PloS one · 2018Article
- Heat shock proteins and chronic fatigue in primary Sjögren's syndrome.Innate immunity · 2016Article
- Toll-like receptor 4 signaling in neurons of trigeminal ganglion contributes to nociception induced by acute pulpitis in rats.Scientific reports · 2015Article
- Involvement of TRPV1 and TRPA1 in incisional intraoral and extraoral pain.Journal of dental research · 2015Article
- Melatonin attenuates inflammation of acute pulpitis subjected to dental pulp injury.American journal of translational research · 2015Article
- Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe purpose of the present study is to evaluate the mechanisms underlying tongue-referred pain associated with tooth pulp inflammation.
methodUsing mechanical and temperature stimulation following dental surgery, we have demonstrated that dental inflammation and hyperalgesia correlates with increased immunohistochemical staining of neurons for TLR4 and HSP70.
resultsMechanical or heat hyperalgesia significantly enhanced in the ipsilateral tongue at 1 to 9 days after complete Freund's adjuvant (CFA) application to the left lower molar tooth pulp compared with that of sham-treated or vehicle-applied rats. The number of fluorogold (FG)-labeled TLR4-immunoreactive (IR) cells was significantly larger in CFA-applied rats compared with sham-treated or vehicle-applied rats to the molar tooth. The number of heat shock protein (Hsp) 70-IR neurons in trigeminal ganglion (TG) was significantly increased on day 3 after CFA application compared with sham-treated or vehicle-applied rats to the molar tooth. About 9.2% of TG neurons were labeled with DiI applied to the molar tooth and FG injected into the tongue, and 15.4% of TG neurons were labeled with FG injected into the tongue and Alexa-labeled Hsp70-IR applied to the tooth. Three days after Hsp70 or lipopolysaccharide (LPS) application to the tooth in naive rats, mechanical or heat hyperalgesia was significantly enhanced compared with that of saline-applied rats. Following successive LPS-RS, an antagonist of TLR4, administration to the TG for 3 days, the enhanced mechanical or heat hyperalgesia was significantly reversed compared with that of saline-injected rats. Noxious mechanical responses of TG neurons innervating the tongue were significantly higher in CFA-applied rats compare with sham rats to the tooth. Hsp70 mRNA levels of the tooth pulp and TG were not different between CFA-applied rats and sham rats.
conclusionsThe present findings indicate that Hsp70 transported from the tooth pulp to TG neurons or expressed in TG neurons is released from TG neurons innervating inflamed tooth pulp, and is taken by TG neurons innervating the tongue, suggesting that the Hsp70-TLR4 signaling in TG plays a pivotal role in tongue-referred pain associated with tooth pulp inflammation.
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Registered trials
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