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 L.; Tao, Feng

doi:10.1007/s12035-018-1076-y

Cited by 32 publications

(40 citation statements)

References 37 publications

(43 reference statements)

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“…IL-1β is key cytokine and plays an essential role in the central sensitization and hyperalgesia [32]. The upregulation of TNF-α expression induced by an intra-temporomandibular joint CFA (Complete Freund's Adjuvant) injection in the Vc has been reported [33]. In our study, we observed high production of TNF-α, IL-1β, and IL-6 in response to pulp exposure, on day 21 after DPI.…”

Section: Neuroinflammatory Profile After Pulp Exposuresupporting

confidence: 60%

Analgesic and Neuroprotective Effects of Electroacupuncture in a Dental Pulp Injury Model—A Basic Research

Romero

Lee

Fuh

et al. 2020

IJMS

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Irreversible pulpitis is an extremely painful condition and its consequence in the central nervous system (CNS) remains unclear. A mouse model of dental pulp injury (DPI) resembles the irreversible pulpitis profile in humans. This study sought to determine whether pain induced by DPI activates microglia and astrocytes in the trigeminal subnucleus caudalis (Vc), as well as increases levels of proinflammatory cytokines, and whether electroacupuncture (EA) can be a potential analgesic and neuroprotective therapy following DPI. Pain behavior was measured via head-withdrawal threshold (HWT) and burrowing behavior at days 1, 3, 7, 14 and 21 after DPI. A marked decrease in HWT and burrowing activity was observed from day 1 to 14 after DPI and no changes were seen on day 21. Microglial and astrocytes activation; along with high cytokine (TNFα, IL-1β, and IL-6) levels, were observed in the Vc at 21 days after DPI. These effects were attenuated by verum (local and distal) EA, as well as oral ibuprofen administration. The results suggest that DPI-induced pain and glial activations in the Vc and EA exert analgesic efficacy at both local and distal acupoints. Furthermore, verum (local and distal) EA might be associated with the modulations of microglial and astrocytes activation.

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Section: Neuroinflammatory Profile After Pulp Exposuresupporting

confidence: 60%

Analgesic and Neuroprotective Effects of Electroacupuncture in a Dental Pulp Injury Model—A Basic Research

Romero

Lee

Fuh

et al. 2020

IJMS

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“…It is possible, however, that there may be site or model specific differences. MGS was only transiently elevated following Complete Freund's Adjuvant inflammation of the TMJ 38 , which does not have ongoing infection occurring in the model. In terms of change in the score, our data reflect a similar to slightly greater increase in MGS as compared to tooth movement 35 , and potentially within the lower end of ranges reported for an exogenous-CGRP migraine model 39 and neuropathic injury of the infraorbital trigeminal nerve 37 .…”

Section: Discussionmentioning

confidence: 90%

Evoked and spontaneous pain assessment during tooth pulp injury

Rossi

See

Foster

et al. 2020

Sci Rep

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injury of the tooth pulp is excruciatingly painful and yet the receptors and neural circuit mechanisms that transmit this form of pain remain poorly defined in both the clinic and preclinical rodent models. Easily quantifiable behavioral assessment in the mouse orofacial area remains a major bottleneck in uncovering molecular mechanisms that govern inflammatory pain in the tooth. In this study we sought to address this problem using the Mouse Grimace Scale and a novel approach to the application of mechanical Von frey hair stimuli. We use a dental pulp injury model that exposes the pulp to the outside environment, a procedure we have previously shown produces inflammation. Using RNAscope technology, we demonstrate an upregulation of genes that contribute to the pain state in the trigeminal ganglia of injured mice. We found that mice with dental pulp injury have greater Mouse Grimace Scores than sham within 24 hours of injury, suggestive of spontaneous pain. We developed a scoring system of mouse refusal to determine thresholds for mechanical stimulation of the face with Von Frey filaments. This method revealed that mice with a unilateral dental injury develop bilateral mechanical allodynia that is delayed relative to the onset of spontaneous pain. This work demonstrates that tooth pain can be quantified in freely behaving mice using approaches common for other types of pain assessment. Harnessing these assays in the orofacial area during gene manipulation should assist in uncovering mechanisms for tooth pulp inflammatory pain and other forms of trigeminal pain.

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“…Recent study with functional neuroimaging has consistently demonstrated altered central pain perception in the brain of patients with FMS [ 5 ]. Accumulated studies have demonstrated that either orofacial inflammation or stress may affect the same areas specific for central pain processing and modulation [ 29 , 30 ]. In our comorbid pain model, we hypothesize that stress signal input could concurrently enhance or prolong the masseter muscle inflammation-induced neuronal hyperactivity in supraspinal pain pathway, integrally resulting in central sensitization in the spinal dorsal horn through the descending brainstem modulatory system.…”

Section: Discussionmentioning

confidence: 99%

Contribution of central sensitization to stress-induced spreading hyperalgesia in rats with orofacial inflammation

Yang

Wei

et al. 2020

Mol Brain

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Temporomandibular disorder (TMD) is commonly comorbid with fibromyalgia syndrome (FMS). The incidence of these pain conditions is prevalent in women and prone to mental stress. Chronic pain symptoms in patients with FMS and myofascial TMD (mTMD) are severe and debilitating. In the present study, we developed a new animal model to mimic the comorbidity of TMD and FMS. In ovariectomized female rats, repeated forced swim (FS) stress induced mechanical allodynia and thermal hyperalgesia in the hindpaws of the 17β-estradiol (E2) treated rats with orofacial inflammation. Subcutaneous injection of E2, injection of complete Freund’s adjuvant (CFA) into masseter muscles or FS alone did not induce somatic hyperalgesia. We also found that the somatic hyperalgesia was accompanied by upregulation of GluN1 receptor and serotonin (5-hydroxytryptamine, 5-HT) 3A receptor expression in the dorsal horn of spinal cord at L4-L5 segments. Intrathecal injection of N-methyl-D-aspartic acid receptor (NMDAR) antagonist 2-amino-5-phosphonovaleric acid (APV) or 5-HT 3 receptor antagonist Y-25130 blocked stress-induced wide-spreading hyperalgesia. These results suggest that NMDAR-dependent central sensitization in the spinal dorsal horn and 5-HT-dependent descending facilitation contribute to the development of wide-spreading hyperalgesia in this comorbid pain model.

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

Cited by 32 publications

References 37 publications

Analgesic and Neuroprotective Effects of Electroacupuncture in a Dental Pulp Injury Model—A Basic Research

Analgesic and Neuroprotective Effects of Electroacupuncture in a Dental Pulp Injury Model—A Basic Research

Evoked and spontaneous pain assessment during tooth pulp injury

Contribution of central sensitization to stress-induced spreading hyperalgesia in rats with orofacial inflammation

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