title: Toll-like receptor 4 signaling in neurons of trigeminal ganglion contributes to nociception induced by acute pulpitis in rats.
abstract: Pain caused by acute pulpitis (AP) is a common symptom in clinical settings. However, its underlying mechanisms have largely remained unknown. Using AP model, we demonstrated that dental injury caused severe pulp inflammation with up-regulated serum IL-1β. Assessment from head-withdrawal reflex thresholds (HWTs) and open-field test demonstrated nociceptive response at 1 day post injury. A consistent up-regulation of Toll-like receptor 4 (TLR4) in the trigeminal ganglion (TG) ipsilateral to the injured pulp was found; and downstream signaling components of TLR4, including MyD88, TRIF and NF-κB, and cytokines such as TNF-α and IL-1β, were also increased. Retrograde labeling indicated that most TLR4 positve neuron in the TG innnervated the pulp and TLR4 immunoreactivity was mainly in the medium and small neurons. Double labeling showed that the TLR4 expressing neurons in the ipsilateral TG were TRPV1 and CGRP positive, but IB4 negative. Furthermore, blocking TLR4 by eritoran (TLR4 antagonist) in TGs of the AP model significantly down-regulated MyD88, TRIF, NF-κB, TNF-α and IL-1β production and behavior of nociceptive response. Our findings suggest that TLR4 signaling in TG cells, particularly the peptidergic TRPV1 neurons, plays a key role in AP-induced nociception, and indicate that TLR4 signaling could be a potential therapeutic target for orofacial pain.
authors.affiliation: 1] Department of Neurology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710004, China [2] Department of Neurobiology and Collaborative Innovation Center for Brain Science, School of Basic Medicine, The Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Jia-Ji
authors.initials: JJ
authors.lastname: Lin
authors.affiliation: 1] State Key Laboratory of Military Stomatology, Department of Operative Dentistry and Endodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, 710032,China [2] Department of Endodontics, Jinan Stomatological Hospital, Jinan, 250001, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Du
authors.affiliation: 1] Department of Cardio-Thoracic Surgery, Kunming General Hospital of Chengdu Military Region, Kunming, 650000, China [2] Department of Neurology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710004, China.
authors.forename: Wen-Ke
authors.initials: WK
authors.lastname: Cai
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Operative Dentistry and Endodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, 710032,China.
authors.forename: Rong
authors.initials: R
authors.lastname: Kuang
authors.affiliation: Department of Neurology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710004, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Chang
authors.affiliation: Department of Neurology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710004, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710004, China.
authors.forename: Yong-Xiang
authors.initials: YX
authors.lastname: Yang
authors.affiliation: Department of Neurology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710004, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Neurology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710004, China.
authors.forename: Zhu-Yi
authors.initials: ZY
authors.lastname: Li
authors.affiliation: Department of Neurobiology and Collaborative Innovation Center for Brain Science, School of Basic Medicine, The Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Kuang
mesh_terms: D000818:Animals; D003782:Dental Pulp / Q000378:metabolism / Q000473:pathology; D004187:Disaccharides / Q000494:pharmacology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000097:blood / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D059225:Nociception / Q000187:drug effects; D011671:Pulpitis / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013403:Sugar Phosphates / Q000494:pharmacology; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012668:Trigeminal Ganglion / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D004187:Disaccharides; D053583:Interleukin-1beta; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D013403:Sugar Phosphates; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C512420:eritoran