歯の機械的刺激による神経興奮を放射断層撮影法を用いて検討した予備研究

Dentists often cannot objectively find abnormalities in patients who complain of discomfort or abnormal sensation in their dental occlusion. We hypothesized that abnormal neural transmission from the tooth is related to this occlusal discomfort sensation. Chronic tooth contact habits may induce neural excitation from the tooth to the central nervous system, and may aggravate the sensation of discomfort in the central nervous system. However, the details of neural transmission from the tooth to the central nervous system are still unclear. In this study, we stimulated a rat premolar mechanically and observed activated bran sites using positron emission tomography (PET) and 18F-2-fluoro-2-deoxy-D-glucose (FDG). We anesthetized 5-7-week-old male rats using isoflurane inhalation anesthesia and stimulated the upper right premolar mechanically with an electric von Frey system (Model 1601C, IITC Instruments) by measuring mechanical pressure. Before the tooth mechanical stimulation, we injected FDG through the rat’s caudal vein and then used a stimulation intensity of 100, 200 or 300 g. We recorded FDG accumulation with PET. The PET brain images were separated into four parts (right higher, left higher, right lower and left lower) for analysis and the peak value of striatal uptake (SUV) in each part was analyzed. The PET images showed that the accumulated FDG in the right lower part of the brain was higher with 300 g tooth stimulation than with 100 or 200 g. The data showed that the tooth stimulation site in the lower part of the brain was activated with tooth stimulation by comparing it with the other parts. We also measured SUV in the right and left sensory areas, motor area, hippocampus, trigeminal ganglia (TG) and spinal cord. The TG and sensory area showed more FDG accumulation compared with mouth opening.咬合違和感を訴えて来院した患者に対して，歯科医師は咬合状態に客観的な異常を見つけることができないこともよくある．我々は歯からの神経伝達が咬合違和感と何らかの関連をしているのではないかと仮説を立てて研究を行っている．慢性的な歯への刺激が歯から中枢における神経興奮に関連しており，中枢での咬合違和感を悪化させるのかもしれないと考えられる．しかしながら，歯から中枢への神経伝達の詳細は不明である．この研究ではラットの小臼歯を機械的に刺激して，脳の活動部位を18F-2-フルオロ-2-デオキシ-D-グルコース （FDG）を用いて放射断層撮影法（PET）により計測した．5〜7 週齢のラットをイソフルレンを用いて全身麻酔し，電気的フォンフレイ刺激装置を用いて刺激圧を計測しながら上顎右側小臼歯を刺激した．歯の刺激前にFDG を尾静脈から注射し，100，200，300g の刺激力を用いて刺激した． 脳PET 画像は脳を4 分割（右上，左上，右下，左下）して，ピーク値を計測したところ，右下部においては300g の刺激力は100，200g よりもFDG の集積が観察された．この結果は歯の刺激により脳の右下部位が活動することを示していると考えられる．また，知覚部位，運動部位，海馬，三叉神経節，脊髄に分類して観察したところ，三叉神経節と知覚部位においてFDG の集積が観察された

Role of CGRP in Neuroimmune Interaction via NF-κB Signaling Genes in Glial Cells of Trigeminal Ganglia

Activation of the trigeminal system causes the release of various neuropeptides, cytokines, and other immune mediators. Calcitonin gene-related peptide (CGRP), which is a potent algogenic mediator, is expressed in the peripheral sensory neurons of trigeminal ganglion (TG). It affects the inflammatory responses and pain sensitivity by modulating the activity of glial cells. The primary aim of this study was to use array analysis to investigate the effect of CGRP on the glial cells of TG in regulating nuclear factor kappa B (NF-κB) signaling genes and to further check if CGRP in the TG can affect neuron-glia activation in the spinal trigeminal nucleus caudalis. The glial cells of TG were stimulated with CGRP or Minocycline (Min) + CGRP. The effect on various genes involved in NF-κB signaling pathway was analyzed compared to no treatment control condition using a PCR array analysis. CGRP, Min + CGRP or saline was directly injected inside the TG and the effect on gene expression of Egr1, Myd88 and Akt1 and protein expression of cleaved Caspase3 (cleav Casp3) in the TG, and c-Fos and glial fibrillary acidic protein (GFAP) in the spinal section containing trigeminal nucleus caudalis was analyzed. Results showed that CGRP stimulation resulted in the modulation of several genes involved in the interleukin 1 signaling pathway and some genes of the tumor necrosis factor pathway. Minocycline pre-treatment resulted in the modulation of several genes in the glial cells, including anti-inflammatory genes, and neuronal activation markers. A mild increase in cleav Casp3 expression in TG and c-Fos and GFAP in the spinal trigeminal nucleus of CGRP injected animals was observed. These data provide evidence that glial cells can participate in neuroimmune interaction due to CGRP in the TG via NF-κB signaling pathway

Prevalence of Posterior Disc Displacement of the Temporomandibular Joint in Patients with Temporomandibular Disorders : A Systematic Review and Meta-Analyses

Aims: To assess the prevalence of posterior disc displacement (PDD) in patients with temporomandibular disorders (TMD) through a systematic review of the literature and meta-analysis, as well as to assess features associated with PDD such as chief complaint, signs and symptoms, morphologic condyle and disc alterations, and PDD management. Methods: A systematic literature search was performed in the US National Library of Medicine’s PubMed/MEDLINE and Cochrane Library databases to identify all peer-reviewed, English-language manuscripts related to PDD. A critical appraisal checklist provided by the Joanna Briggs Institue (JBI) for studies reporting prevalence data was used to assess the quality of the included manuscripts. A meta-analysis was conducted using software MetaXL 5.3 (EpiGear International Pty Ltd) add-in for Microsoft Excel. Pooled prevalence and 95% confidence intervals (CIs) were calculated using the software. Heterogeneity of the included studies was assessed using the Higgins I2 test and Cochran’s Q (with P value; < .05 was considered significant). Results: A total of 21 articles were selected for qualitative data synthesis: 2 case reports, 14 observational studies, and 5 studies that reported PDD in various conditions. Quantitative data analysis was performed for the 14 observational studies, of which 13 reported prevalence with respect to the number of joints affected and 9 reported prevalence with respect to the number of patients affected. The overall pooled prevalence of PDD for the number of joints affected was 0.7% (95% CI: 0.005 to 0.008). The pooled prevalence of PDD for the number of patients was 0.9% (95% CI: 0.007 to 0.011). PDD was found to be associated with osseous changes, including changes in the morphology of the condyle, disc, and articular eminence; osseous abnormalities (erosion, osteophytes); and joint effusion. Conclusion: This meta-analysis showed a very low prevalence rate of PDD in TMD patients. The limited literature did not allow conclusions to be drawn about the PDD-related features

The role of chemical transmitters in neuron-glia interaction and pain in sensory ganglion

Neuropathic pain (NP) develops because of damage to the peripheral or central nervous system. It results in the hyperalgesia and allodynia. In the recent years, various researchers have studied the involvement of neuro-immune system in causing persistence of pain. The absence of synaptic contacts in the sensory ganglion makes them distinctive in terms of pain related signalling. In sensory ganglia, the neurotransmitters or the other modulators such as inflammatory substances produced by the ganglion cells, because of an injury, are responsible for the cross-excitation between neurons and neuron-glial interaction, thus affecting chemical transmission. This chemical transmission is considered mainly responsible for the chronicity and the persistent nature of neuropathic pain. This review examines the pain signalling due to neurotransmitter or cytokine release within the sensory ganglia. The specific areas focused on include: 1) the role of neurotransmitters released from the somata of sensory neurons in pain , 2) neuron-glia interaction and 3) role of cytokines in neuromodulation and pain

CGRPは三叉神経節衛星グリア細胞からのサイトカイン遊離と口腔顔面侵害性疼痛を誘発する

Neuron-glia interactions contribute to pain initiation and sustainment. Intra-ganglionic (IG) secretion of calcitonin gene-related peptide (CGRP) in the trigeminal ganglion (TG) modulates pain transmission through neuron-glia signaling, contributing to various orofacial pain conditions. The present study aimed to investigate the role of satellite glial cells (SGC) in TG in causing cytokine-related orofacial nociception in response to IG administration of CGRP. For that purpose, CGRP alone (10 μL of 10-5 M), Minocycline (5 μL containing 10 μg) followed by CGRP with one hour gap (Min + CGRP) were administered directly inside the TG in independent experiments. Rats were evaluated for thermal hyperalgesia at 6 and 24 h post-injection using an operant orofacial pain assessment device (OPAD) at three temperatures (37, 45 and 10 ℃). Quantitative real-time PCR was performed to evaluate the mRNA expression of IL-1β, IL-6, TNF-α, IL-1 receptor antagonist (IL-1RA), sodium channel 1.7 (NaV 1.7, for assessment of neuronal activation) and glial fibrillary acidic protein (GFAP, a marker of glial activation). The cytokines released in culture media from purified glial cells were evaluated using antibody cytokine array. IG CGRP caused heat hyperalgesia between 6–24 h (paired-t test, p < 0.05). Between 1 to 6 h the mRNA and protein expressions of GFAP was increased in parallel with an increase in the mRNA expression of pro-inflammatory cytokines IL-1β and anti-inflammatory cytokine IL-1RA and NaV1.7 (one-way ANOVA followed by Dunnett’s post hoc test, p < 0.05). To investigate whether glial inhibition is useful to prevent nociception symptoms, Minocycline (glial inhibitor) was administered IG 1 h before CGRP injection. Minocycline reversed CGRP-induced thermal nociception, glial activity, and down-regulated IL-1β and IL-6 cytokines significantly at 6 h (t-test, p < 0.05). Purified glial cells in culture showed an increase in release of 20 cytokines after stimulation with CGRP. Our findings demonstrate that SGCs in the sensory ganglia contribute to the occurrence of pain via cytokine expression and that glial inhibition can effectively control the development of nociception

歯科インプラント周囲の骨吸収に関する臨床疫学研究

Background: During functional loading, the design of the dental implant may have an effect on the response of marginal bone. Objectives: The purpose of this study was to report the prevalence of peri-implantitis, and to compare radiographic parameters around Brånemark and Replace Select dental implants and evaluate whether disparities in the morphologic features of these two indistinct implant systems, particularly their abutment-implant attachment, had an influence on the health of surrounding tissues and marginal bone loss (MBL). Materials and Methods: Collection of data was done at the Department of Fixed Prosthodontics, the Department of Maxillo-Facial Prosthodontics, and Oral Implant Center of Tokushima University Hospital, in Tokushima, Japan; between March 2003 and followed until January 2017. Patients who have been treated with the Replace Select internal type implant and the Brånemark variety were selected as cohort. Marginal bone level measurements were evaluated via periapical and panoramic radiographs taken at regular follow-up visit. These dimensions were calculated, starting from the orientation mark at the implant abutment interface to the bottommost perceived contact area of marginal bone with the aforementioned implant system. The change in the level of bone was estimated by calculating the variation involving an initial reference value and the follow-up values. Results: An average loss of bone at 0.65 ± 1.51 mm (range 0.36 to 7.89 mm) in the Replace Select group was observed, while in the Brånemark group 0.7 ± 1.32 mm (range 0.62 to 8.64 mm) was observed. Spearman rank correlation exhibited a statistically significant positive correlation between progress of bone loss around implant body and interval from implantation in the Brånemark group, whereas in the Replace Select group it was not significant. The Brånemark group exhibited significant (P = 0.0269) negative correlation of MBL and its diameters, whereas the Replace Select group did not exhibit such correlation. Conclusion: Within the limits of this study, it can be concluded that deviations in the morphologic attributes of these two diverse implant systems had an influence on the health of surrounding tissues and MBL. The Brånemark implants showed a significant increase in MBL (> 1.8mm) as the time of placement elapses. This marked MBL was greater in females than males, in posterior than in anterior, and in the narrow platform implants than the regular platform implants or the wide platform implants. On the other hand, results suggested that this bone loss was greater in the mandible than the maxilla, in single-unit implant crowns than multiple implant restorations in the Replace Select group

神経障害性疼痛における三叉神経筋内のIL-10とCXCL2

Many trigeminal neuropathic pain patients suffer severe chronic pain. The neuropathic pain might be related with cross-excitation of the neighboring neurons and satellite glial cell (SGCs) in the sensory ganglia and increasing the pain signals from the peripheral tissue to the central nervous system. We induced trigeminal neuropathic pain by infraorbital nerve constriction injury (IONC) in Sprague-Dawley rats. We tested cytokine (CXCL2 and IL-10) levels in trigeminal ganglia (TGs) after trigeminal neuropathic pain induction, and the effect of direct injection of the anti-CXCL2 and recombinant IL-10 into TG. We found that IONC induced pain behavior. Additionally, IONC induced satellite glial cell activation in TG and cytokine levels of TGs were changed after IONC. CXCL2 levels increased on day 1 of neuropathic pain induction and decreased gradually, with IL-10 levels showing the opposite trend. Recombinant IL-10 or anti-CXCL2 injection into TG decreased pain behavior. Our results show that IL-10 or anti-CXCL2 are therapy options for neuropathic pain

片側末梢投与されたA型ボツリヌス毒素は動物モデルにおいて両側三叉神経節に局在する

Peripheral nerve injury leads to sensory ganglion hyperexcitation, which increases neurotransmitter release and neuropathic pain. Botulinum toxin type A (BoNT/A) regulates pain transmission by reducing neurotransmitter release, thereby attenuating neuropathic pain. Despite multiple studies on the use of BoNT/A for managing neuropathic pain in the orofacial region, its exact mechanism of transport remains unclear. In this study, we investigated the effects of BoNT/A in managing neuropathic pain in two different animal models and its transport mechanism in the trigeminal nerve. Intraperitoneal administration of cisplatin induced bilateral neuropathic pain in the orofacial region, reducing the head withdrawal threshold to mechanical stimulation. Unilateral infraorbital nerve constriction (IONC) also reduced the ipsilateral head withdrawal threshold to mechanical stimulation. Unilateral peripheral administration of BoNT/A to the rat whisker pad attenuated cisplatin-induced pain behavior bilaterally. Furthermore, contralateral peripheral administration of BoNT/A attenuated neuropathy-induced behavior caused by IONC. We also noted the presence of BoNT/A in the blood using the mouse bioassay. In addition, the Alexa Fluor-488-labeled C-terminal half of the heavy chain of BoNT/A (BoNT/A-Hc) was localized in the neurons of the bilateral trigeminal ganglia following its unilateral administration. These findings suggest that axonal and hematogenous transport are involved in the therapeutic effects of peripherally administered BoNT/A in the orofacial region

Collarless metal ceramic restorations to obscure the umbrella effect

Esthetics with porcelain fused to metal restoration in the anterior region can be adversely affected due to the inadequate teeth preparations and design of the prosthesis. We presented here a case report where esthetics was compromised due to darkening of the interdental papilla and marginal gingival and overcontoured restorations in relation to porcelain fused to metal restorations. Good esthetic results were obtained by using basic principles of tooth preparation and using collarless metal ceramic restorations

Stress pattern generated by different post and core material combinations: A photoelastic study

Objective: To analyze the effect of different combinations of post and core materials on stress distribution in dentin of an endodontically treated tooth. Materials and Methods: This was an experimental stress analysis study. Models were made in photoelastic material, i.e., epoxy resin. Different combinations of post and core materials used were: Glass fiber post with composite core, stainless steel post with composite core, and cast metal post and core. Stresses generated were frozen, models were sliced and viewed under circular polariscope, and photographs were taken. Stress was calculated by counting the number of fringes. Results: For the combination of glass fiber post with composite core, the shear stresses calculated were 1.196, 1.196, and 2.898 MPa in the apical, mid-root, and cervical region, respectively. For the combination of stainless steel post with composite core, the apical, mid-root and cervical stresses were 1.534, 0.511, and 2.557 MPa, respectively. For cast metal post and core, the apical, mid-root, and cervical stresses were 0.852, 0.511, and 1.534 MPa, respectively. Conclusion: The cervical region of the teeth is subjected to the highest stresses irrespective of the material used. The stainless steel post with the composite core generated the highest stress concentration in different regions. A glass fiber post generated a uniform stress distribution. A cast metal post and core combination generated lesser stress than the other combinations. The vast difference in the elastic modulus of the restorative materials can lead to nonuniform stress distribution and concentration of stresses in different areas which can have deleterious effect on the survival of already compromised teeth and restoration. Such combinations should be avoided and the material which has an elastic modulus close to that of dentin should be preferred