Advance in Functional Restoration of Injured Nerve with Low Level Laser and its Utilization in the Dental and Maxillofacial Region.

The inferior alveolar nerve and facial nerve are the two most important nerves in the dental and maxillofacial region. The injury to them is one of the major postoperative complications after alveolar surgery and orthognathic surgery. However, recovering the nerve function after injury takes a long time and the recovery effect tends to be unsatisfactory. In recent years, an intensively investigated technique, low level laser which has been applying in assisting the recovery of nerve function, has been gradually proved to be effective in clinically treating postoperative nerve injury. In this article we review in terms of the mechanisms involved in low level laser-assisted functional restoration of nerve injury and its clinical application in the recovery of nerve function in the dental and maxillofacial area as well.

Analysis of Tooth Innervation in Microfluidic Coculture Devices.

Innervation plays a key role in the development, homeostasis, and regeneration of organs and tissues. However, the mechanisms underlying these phenomena are not well understood yet. In particular, the role of innervation in tooth development and regeneration is neglected. Cocultures constitute a valuable method to investigate and manipulate the interactions between nerve fibers and teeth in a controlled and isolated environment. Microfluidic systems for allow cocultures of neurons and different cell types in their appropriate culture media, while permitting the passage of axons from one compartment to the other. Here we describe how to isolate and coculture developing trigeminal ganglia and tooth germs in a microfluidic coculture system. This protocol describes a simple and flexible way to coculture ganglia/nerves and their target tissues and to study the roles of specific molecules on such interactions in a controlled and isolated environment.

Establishment of tooth blood supply and innervation is developmentally regulated and takes place through differential patterning processes.

Teeth are richly supported by blood vessels and peripheral nerves. The aim of this study was to describe in detail the developmental time-course and localization of blood vessels during early tooth formation and to compare that to innervation, as well as to address the putative role of vascular endothelial growth factor (VEGF), which is an essential regulator of vasculature development, in this process. The localization of blood vessels and neurites was compared using double immunofluorescence staining on sections at consecutive stages of the embryonic (E) and postnatal (PN) mandibular first molar tooth germ (E11-PN7). Cellular mRNA expression domains of VEGF and its signaling receptor VEGFR2 were studied using sectional radioactive in situ hybridization. Expression of VEGF mRNA and the encoded protein were studied by RT-PCR and western blot analysis, respectively, in the cap and early bell stage tooth germs, respectively. VEGFR2 was immunolocalized on tooth tissue sections. Smooth muscle cells were investigated by anti-alpha smooth muscle actin (αSMA) antibodies. VEGF showed developmentally regulated epithelial and mesenchymal mRNA expression domains including the enamel knot signaling centers that correlated with the growth and navigation of the blood vessels expressing Vegfr2 and VEGFR2 to the dental papilla and enamel organ. Developing blood vessels were present in the jaw mesenchyme including the presumptive dental mesenchyme before the appearance of the epithelial dental placode and dental neurites. Similarly, formation of a blood vessel plexus around the bud stage tooth germ and ingrowth of vessels into dental papilla at E14 preceded ingrowth of neurites. Subsequently, pioneer blood vessels in the dental papilla started to receive smooth muscle coverage at the early embryonic bell stage. Establishment and patterning of the blood vessels and nerves during tooth formation are developmentally regulated, stepwise processes that likely involve differential patterning mechanisms. Development of tooth vascular supply is proposed to be regulated by local, tooth-specific regulation by epithelial-mesenchymal tissue interactions and involving tooth target expressed VEGF signaling. Further investigations on tooth vascular development by local VEGF signaling, as well as how tooth innervation and development of blood vessels are integrated with advancing tooth organ formation by local signaling mechanisms, are warranted.

Bone Marrow Stromal Cells Promote Innervation of Bioengineered Teeth.

Transplantation of bone marrow mesenchymal stem cells (BMDCs) into a denervated side of the spinal cord was reported to be a useful option for axonal regeneration. The innervation of teeth is essential for their function and protection but does not occur spontaneously after injury. Cultured reassociations between dissociated embryonic dental mesenchymal and epithelial cells and implantation lead to a vascularized tooth organ regeneration. However, when reassociations were coimplanted with a trigeminal ganglion (TG), innervation did not occur. On the other hand, reassociations between mixed embryonic dental mesenchymal cells and bone marrow-derived cells isolated from green fluorescent protein (GFP) transgenic mice (BMDCs-GFP) (50/50) with an intact and competent dental epithelium (ED14) were innervated. In the present study, we verified the stemness of isolated BMDCs, confirmed their potential role in the innervation of bioengineered teeth, and analyzed the mechanisms by which this innervation can occur. For that purpose, reassociations between mixed embryonic dental mesenchymal cells and BMDCs-GFP with an intact and competent dental epithelium were cultured and coimplanted subcutaneously with a TG for 2 wk in ICR mice. Axons entered the dental pulp and reached the odontoblast layer. BMDCs-GFP were detected at the base of the tooth, with some being present in the pulp associated with the axons. Thus, while having a very limited contribution in tooth formation, they promoted the innervation of the bioengineered teeth. Using quantitative reverse transcription polymerase chain reaction and immunostainings, BMDCs were shown to promote innervation by 2 mechanisms: 1) via immunomodulation by reducing the number of T lymphocytes (CD3+, CD25+) in the implants and 2) by expressing neurotrophic factors such as NGF, BDNF, and NT3 for axonal growth. This strategy using autologous mesenchymal cells coming from bone marrow could be used to innervate bioengineered teeth without treatment with an immunosuppressor such as cyclosporine A (CsA), thus avoiding multiple side effects.

Prevalence and measurement of anterior loop of the mandibular canal using CBCT: A cross sectional study.

BACKGROUND: Anterior loop of the mental nerve is a very important anatomic landmark in implant placement and anterior mandibular osteotomies. PURPOSE: Two-dimensional imaging techniques are not competent enough to locate and measure the mental nerve loop in majority of the cases. Any injury to this loop results in pain/paresthesia/numbness in the region supplied by the mental nerve. The aim of this study is to analyze the prevalence and measure the length of the loop using cone beam computerized tomography (CBCT) and calculate the average length and prevalence so that a safe margin can be given while placing the implants or the osteotomy cuts in the premolar region. MATERIALS AND METHODS: A cross-sectional study was done using CBCT images of 85 patients taken for impaction surgery. The length of the loop was measured in mm using standardized lines drawn along specific anatomic landmarks. RESULTS: In our study 11.76% of patients had anterior loop in their mental nerve. Mean length of the mental nerve loop was calculated and found to be 2.79 mm. CONCLUSION: A margin of 4 mm anterior to the mental foramen should be safe to avoid any damage to the mental nerve loop bundle in majority of the cases where the loop is present.

Computer-guided chin harvest: A novel approach for autogenous block harvest from the mandibular symphesis.

BACKGROUND: The introduction of CAD/CAM technology allowed clinicians to carry out complex procedures with a high level of precision and reproducibility and minimize the risk of injury during the procedure. PURPOSE: The aim of the present study is to evaluate the efficacy of the CAD/CAM surgical guide during chin harvesting procedures in reducing the risk of neurosensory damage and patient morbidity compared with the standard technique. MATERIALS AND METHODS: About 20 cases of autogenous block chin harvest were randomly into two groups. The first group received computer-guided chin block harvest while the second group received autogenous block chin harvest using the standard approach. RESULTS: In the guided group, out of the 10 subjects, 2 subjects presented with wound dehiscence which resolved within 1 month. No teeth showed any negative pulp sensitivity results. The pointed-Blunt test and 2 point discrimination tests showed a single case of neurodeficits at 1 week follow-up appointment which resolved within 1 month. In the nonguided group, out of the 10 subjects, 1 case presented with wound dehiscence that resolved completely within 1 month. Pulp vitality test showed negative results in 29.4% of the involved teeth at 1 week which decreased to 9.8% and 3.9% at 1 and 6 months follow-up, respectively. The pointed blunt test revealed 3 subjects with neurodeficits at 1 week, out of which 2 subjects showed persisting symptoms at 6 months follow-up. The 2 point discrimination test showed 3 subjects with neurodeficits, out of which two subjects showed persistent symptoms with no resolution at the 6 months follow-up. CONCLUSION: Within the limits of this study, computer-guided chin harvest shows promising results in the reduction of neurosensory complications following harvesting procedures and presents as a safe alternative to the standard technique.

The Effect of Sensory Innervation on the Inorganic Component of Bones and Teeth; Experimental Denervation - Review.

The effect of the nervous system on bone remodelling has been described by many studies. Sensory and autonomic nerves are present in the bone. Immunohistochemical analysis of the bone have indicated the presence of neuropeptides and neurotransmitters that act on bone cells through receptors. Besides carrying sensory information, sensory neurons produce various neuropeptides playing an important role in maintaining bone and tooth pulp homeostasis, and dentin formation. Bone tissue and teeth contain organic and inorganic components. Bone cells enable bone mineralization and ensure its formation and resorption. Studies focused on the effects of the nervous system on the bone are proceeded using various ways. Sensory denervation itself can be achieved using capsaicin causing chemical lesion to the nerve. Surgical ways of causing only sensory lesion to nerves are substantially limited because many peripheral nerves are mixed and contain a motor component as well. From this point of view, the experimental model with transection of inferior alveolar nerve is appropriate. This nerve provides sensory innervation of the bone and teeth of the mandible. The purpose of our paper is to provide an overview of the effects exerted by the nervous system on the inorganic component of the bone and teeth, and also to present an overview of the used experimental models. As we assume, the transection of inferior alveolar nerve could be reflected in changed contents and distribution of chemical elements in the bone and teeth of rat mandible. This issue has not been studied so far.

Physiological profiles of cortical responses to mechanical stimulation of the tooth in the rat: An optical imaging study.

The periodontal ligament (PDL) includes several types of nerve endings, such as Aß-, Aδ-, and C-fibers, which play critical roles in detecting the strength and direction of occlusal force. Previous studies have demonstrated that electrical stimulation of the PDL activates the somatosensory and insular cortices. However, the profile of cortical excitation in response to mechanical PDL stimulation mostly remains unknown. To investigate the differences in cortical responses to electrical and mechanical stimulation of the maxillary first molar, we performed optical imaging to determine the responding cortical regions in combination with a pharmacological approach. The molar was mechanically stimulated by pulling in the rostral direction, and electrical stimulation was applied via bipolar electrodes inserted into the mesial PDL. Mechanical stimulation initially excited the primary somatosensory cortex (S1), whereas electrical stimulation evoked an initial response between the secondary somatosensory cortex (S2) and insular oral region (IOR). The characteristic feature responding to mechanical stimulation was the rebound response evoked at the end of mechanical stimulation. A longer mechanical stimulation evoked a larger amplitude of the rebound response. A paired-pulse protocol of mechanical stimulation revealed that the amplitude of the second response was smaller than the first response, in accordance with the shorter interstimulus interval. Systemic application of morphine, a potent blocker of nociception, reduced the amplitude of the maximum excitation, particularly in S2/IOR compared to S1. These results suggest that S1 and S2/IOR are principally excited by mechanical and electrical stimulation, respectively, and that S2/IOR is involved in nociception processing.

The Reliability of Panoramic Radiography Versus Cone Beam Computed Tomography when Evaluating the Distance to the Alveolar Nerve in the Site of Lateral Teeth.

BACKGROUND The aim of this study was to compare the reliability of panoramic radiography (PR) and cone beam computed tomography (CBCT) in the evaluation of the distance of the roots of lateral teeth to the inferior alveolar nerve canal (IANC). MATERIAL AND METHODS 100 PR and 100 CBCT images that met the selection criteria were selected from the database. In PR images, the distances were measured using an electronic caliper with 0.01 mm accuracy and white light x-ray film reviewer. Actual values of the measurements were calculated taking into consideration the magnification used in PR images (130%). Measurements on CBCT images were performed using i-CAT Vision software. Statistical data analysis was performed using R software and applying Welch's t-test and the Wilcoxon test. RESULTS There was no statistically significant difference in the mean distance from the root of the second premolar and the mesial and distal roots of the first molar to the IANC between PR and CBCT images. The difference in the mean distance from the mesial and distal roots of the second and the third molars to the IANC measured in PR and CBCT images was statistically significant. CONCLUSIONS PR may be uninformative or misleading when measuring the distance from the mesial and distal roots of the second and the third molars to the IANC.

Promoting bioengineered tooth innervation using nanostructured and hybrid scaffolds.

The innervation of teeth mediated by axons originating from the trigeminal ganglia is essential for their function and protection. Immunosuppressive therapy using Cyclosporine A (CsA) was found to accelerate the innervation of transplanted tissues and particularly that of bioengineered teeth. To avoid the CsA side effects, we report in this study the preparation of CsA loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles, their embedding on polycaprolactone (PCL)-based scaffolds and their possible use as templates for the innervation of bioengineered teeth. This PCL scaffold, approved by the FDA and capable of mimicking the extracellular matrix, was obtained by electrospinning and decorated with CsA-loaded PLGA nanoparticles to allow a local sustained action of this immunosuppressive drug. Dental re-associations were co-implanted with a trigeminal ganglion on functionalized scaffolds containing PLGA and PLGA/cyclosporine in adult ICR mice during 2weeks. Histological analyses showed that the designed scaffolds did not alter the teeth development after in vivo implantation. The study of the innervation of the dental re-associations by indirect immunofluorescence and transmission electron microscopy (TEM), showed that 88.4% of the regenerated teeth were innervated when using the CsA-loaded PLGA scaffold. The development of active implants thus allows their potential use in the context of dental engineering. STATEMENT OF SIGNIFICANCE: Tooth innervation is essential for their function and protection and this can be promoted in vivo using polymeric scaffolds functionalized with immunosuppressive drug-loaded nanoparticles. Immunosuppressive therapy using biodegradable nanoparticles loaded with Cyclosporine A was found to accelerate the innervation of bioengineered teeth after two weeks of implantation.

Integration of tooth morphogenesis and innervation by local tissue interactions, signaling networks, and semaphorin 3A.

The tooth, like many other organs, develops from both epithelial and mesenchymal tissues, and has proven to be a valuable tool with which to investigate organ formation and peripheral innervation. Tooth formation is regulated by local epithelial-mesenchymal tissue interactions, and is closely integrated with stereotypic dental nerve navigation and patterning. Recent analyses of the function and regulation of semaphorin 3A (SEMA3A) have shed light on the regulatory mechanisms that coordinate organogenesis and innervation at the tissue and molecular levels. In the tooth, SEM3A acts as a developmentally regulated secretory chemo-repellent, that controls tooth innervation during embryonic and postnatal development. The tooth germ governs its own innervation by a combination of local tissue interactions and SEMA3A expression. SEMA3A signaling, in turn, is controlled by a number of conserved signaling effectors, including TGF-ß superfamily members, FGF, and WNT; all function in embryo and organ development, and are essential for tooth histo-morphogenesis. Thus, SEMA3A driven axon guidance is integrated into key odontogenic signaling networks, establishing this protein as a critical molecular tether between 2 distinct developmental processes (morphogenesis and sensory innervation), both of which are required to obtain a functional tooth.

A Systematic Review of the Cervical Plexus Accessory Innervation and Its Role in Dental Anesthesia.

INTRODUCTION: Accessory innervation (AI) may account for the persistent sensation perceived after successful mandibular anesthesia in the adult patient. The purpose of this systematic review was to record the quality of evidence pertaining to the cervical plexus (CP) AI in dental anesthesia. MATERIALS AND METHODS: Electronic and manual searches were conducted using Ovid and Medline of articles published from 1922 to March of 2015. Studies written in any language were included as long as they involved: (i) humans, animals, and/or cadavers AND (ii) anatomical and/or research anesthetic-technique approaches and/or clinical approaches. Exclusion criteria were (i) maxillary buccal infiltration, (ii) no abstract/paper available, (iii) studies that do not comprise the description of the branches of the CP branches in dentistry and (iv) duplicated articles. The articles were reviewed and graded by levels of evidence (LOE) through a methodological scoring index (MSI). RESULTS: Forty-four out of 185 papers fulfilled the inclusion criteria. One randomized control trial, 3 comprehensive reviews, 1 cohort study, 5 case series/reports, 16 poor-quality cohort and case series/reports and 18 reviews/case, reports/expert opinions were found. Of the 44 publications, there were 4 LOE 1, 1 LOE 2, 5 LOE 3, 20 LOE 4 and 14 LOE 5 studies. CONCLUSIONS: The MSI helped to classify papers LOE in a standardized and objective approach. The objective evidence quality occurrence recorded was found to be LOE 4 (n = 20) > LOE 5 (n = 14) > LOE 3 (n = 5) > LOE 1 (n = 4) > LOE 2 (n = 1). The anatomy of the CP needs to be reexamined and understood in the anatomical literature.

MR neurographic orthopantomogram: Ultrashort echo-time imaging of mandibular bone and teeth complemented with high-resolution morphological and functional MR neurography.

PURPOSE: Panoramical radiographs or cone-beam computed tomography (CT) are the standard-of-care in dental imaging to assess teeth, mandible, and mandibular canal pathologies, but do not allow assessment of the inferior alveolar nerve itself nor of its branches. We propose a new technique for "MR neurographic orthopantomograms" exploiting ultrashort echo-time (UTE) imaging of bone and teeth complemented with high-resolution morphological and functional MR neurography. MATERIALS AND METHODS: The Institutional Review Board approved the study in 10 healthy volunteers. Imaging of the subjects mandibles at 3.0T (Magnetom Skyra, Siemens-Healthcare) using a 64-channel head coil with isotropic spatial resolution for subsequent multiplanar reformatting, was performed. Bone images were acquired using a 3D PETRA sequence (TE, 0.07 msec). Morphological nerve imaging was performed using a dedicated 3D PSIF and 3D SPACE STIR sequence. Functional MR neurography was accomplished using a new accelerated diffusion-tensor-imaging (DTI) prototype sequence (2D SMS-accelerated RESOLVE). Qualitative and quantitative image analysis was performed and descriptive statistics are provided. RESULTS: Image acquisition and subsequent postprocessing into the MR neurographic orthopantomogram by overlay of morphological and functional images were feasible in all 10 volunteers without artifacts. All mandibular bones and mandibular nerves were assessable and considered normal. Fiber tractography with quantitative evaluation of physiological diffusion properties of mandibular nerves yielded the following mean ± SD values: fractional anisotropy, 0.43 ± 0.07; mean diffusivity (mm(2) /s), 0.0014 ± 0.0002; axial diffusivity, 0.0020 ± 0.0002, and radial diffusivity, 0.0011 ± 0.0001. CONCLUSION: The proposed technique of MR neurographic orthopantomogram exploiting UTE imaging complemented with high-resolution morphological and functional MR neurography was feasible and allowed comprehensive assessment of osseous texture and neural microarchitecture in a single examination. J. Magn. Reson. Imaging 2016;44:393-400.

Double-masked, randomized, placebo-controlled study to evaluate the efficacy and tolerability of intranasal K305 (3% tetracaine plus 0.05% oxymetazoline) in anesthetizing maxillary teeth.

BACKGROUND: The authors compared the local anesthetic efficacy and safety of an intranasally administered formulation of tetracaine and oxymetazoline (K305) with placebo in adult participants undergoing single dental restorative procedures in teeth nos. 4 through 13. METHODS: The authors screened and allocated 150 participants in a double-masked, randomized fashion to either K305 or placebo nasal spray. The authors delivered the study drug as two 0.2-milliliter sprays separated by 4 minutes inside the nostril on the side ipsilateral to the tooth being treated. The authors administered a third 0.2-mL spray, if necessary, and administered 4% articaine with 1:200,000 epinephrine by means of injection if anesthesia was inadequate. Safety evaluations included participant reports of adverse events, vital signs, and alcohol sniff tests during the 2-hour study period and at a 1-day follow-up visit. The primary efficacy end point was anesthetic success defined as the completion of the dental procedure without the need for rescue injectable local anesthetic. The authors evaluated differences in success rates observed between K305 and placebo by using a 1-sided Fisher exact test. RESULTS: The overall success rates were 88.0% (95% confidence interval, 80.0-93.6) and 28% (95% confidence interval, 16.2-42.5) for K305 and placebo, respectively (P < .0001). The most frequent adverse effects in the K305 group were rhinorrhea (57.0%) and nasal congestion (26.0%). No serious adverse events occurred during this study. CONCLUSIONS: K305 was effective and well tolerated during restorative procedures in adult participants. PRACTICAL IMPLICATIONS: K305 provides a needleless alternative for obtaining maxillary pulpal anesthesia on premolars, canines, and incisors.

Enhancement of Analgesic Effect by Combination of Non-Noxious Stimulation and Noxious Stimulation in Humans.

The aim of the this study was to investigate the combined effects of heterosegmental non-noxious and noxious stimulation on electrically induced tooth pain. The late component of somatosensory-evoked potentials (SEP), induced by electrical tooth stimulation and pain intensity, were examined under electrical stimulation to forearms. Noxious, non-noxious, and combined non-noxious and noxious electrical stimulation were applied to median nerves on the forearms. Four experimental sessions (ie, control session, combined non-noxious and noxious stimulation session, non-noxious stimulation session, and noxious stimulation session were performed for each subject at each 10-minute interval for 30 minutes. The amplitudes of the SEP and VAS scores in the combined stimulation session decreased significantly compared with those in the control session and the reduction rates were 51.1% (13.4 µV) and 41.0% (23.5 mm), respectively. These results show that the combined stimulation has a more potent analgesic effect than that of either the non-noxious or the noxious stimulation. It is suggested that a potent analgesia was produced by an activated central mechanism, including endogenous opioid and descending pain inhibitory systems due to combined non-noxious and noxious stimulation.

The innervation of the zebrafish pharyngeal jaws and teeth.

Zebrafish (Danio rerio) teeth are increasingly used as a model to study odontogenesis in non-mammalians. Using serial semi-thin section histology and immunohistochemistry, the nerves innervating the pharyngeal jaws and teeth have been identified. The last pair of branchial arches, which are non-gill bearing but which carry the teeth, are innervated by an internal branch of a post-trematic ramus of the vagal nerve. Another, external, branch is probably responsible for the motor innervation of the branchiomeric musculature. Nerve fibres appear in the pulp cavity of the teeth only late during cytodifferentiation, and are therefore likely not involved in early steps of tooth formation. The precise role of the nervous system during continuous tooth replacement remains to be determined. Nonetheless, this study provides the necessary morphological background information to address this question.

Differential changes in gingival somatosensory sensitivity after painful electrical tooth stimulation.

We aimed to evaluate the effect of painful tooth stimulation on gingival somatosensory sensitivity of healthy volunteers in a randomized, controlled design. Thirteen healthy volunteers (six women, seven men; 28.4 ± 5.0 years) were included for two experimental sessions of electrical tooth stimulation: painful tooth stimulation and tooth stimulation below the sensory threshold (control). Eight of the human subjects participated in a third session without tooth stimulation. In all sessions, the somatosensory sensitivity of the gingiva adjacent to the stimulated tooth was evaluated with a standardized battery of quantitative sensory tests (QST) before, immediately after and 30 min after tooth stimulation. Painful tooth stimulation evoked significant decreases in warmth and heat pain thresholds (P < 0.001) as well as pressure pain thresholds (increased sensitivity) (P = 0.024) and increases in mechanical detection thresholds (decreased sensitivity) (P < 0.050). Similar thermal threshold changes (P < 0.019) but no mechanical changes were found after tooth stimulation below the sensory threshold (P > 0.086). No QST changes were detected in the session without tooth stimulation (P > 0.060). In conclusion, modest increased gingival sensitivity to warmth, painful heat and pressure stimuli as well as desensitization to non-painful mechanical stimulation were demonstrated after tooth stimulation. This suggests involvement of competing heterotopic facilitatory and inhibitory mechanisms. Furthermore, stimulation below the sensory threshold induced similar thermal sensitization suggesting the possibility of activation of axon-reflex-like mechanisms even at intensities below the perception threshold. These findings may have implications for interpretation of somatosensory results in patients with chronic intraoral pain.

Identification and adjustment of experimental occlusal interference using functional magnetic resonance imaging.

BACKGROUND: The purpose of this study was to use functional magnetic resonance imaging (fMRI) to quantify changes in brain activity during experimental occlusal interference. METHODS: Fourteen healthy volunteers performed a rhythmical tapping occlusion task with experimental occlusal interference of the right molar tooth at 0 mm (no occlusion), 0.5 mm, and 0.75 mm. The blood-oxygen-level dependent (BOLD) signal was quantified using statistical parametric mapping and compared between rest periods and task periods. RESULTS: In tapping tasks with experimental occlusal interference of 0.75 mm or 0.5 mm, there was clear activation of the contralateral teeth-related primary sensory cortex and Brodmann's area 46. At 0 and 30 minutes after removal of the experimental occlusal interference, the activation clearly appeared in the bilateral teeth-related primary sensory cortices and Brodmann's area 46. At 60 minutes after the removal of the experimental occlusal interference, the activation of Brodmann's area 46 had disappeared, and only the bilateral teeth-related primary sensory cortices were active. CONCLUSIONS: The present results suggest that adjustments for experimental occlusal interference can be objectively evaluated using fMRI. We expect that this method of evaluating adjustments in occlusal interference, combined with fMRI and the tapping task, could be applied clinically in the future.

Coordination of tooth morphogenesis and neuronal development through tissue interactions: lessons from mouse models.

In addition to being an advantageous model to investigate general molecular mechanisms of organ formation, the tooth is a distinct target organ for peripheral nerve innervation. These nerves are required for the function and protection of the teeth and, as shown in fish, also for their regeneration. This review focuses on recent findings of the local tissue interactions and molecular signaling mechanisms that regulate the early nerve arrival and patterning of mouse mandibular molar tooth sensory innervation. Dental sensory nerve growth and patterning is a stepwise process that is intimately linked to advancing tooth morphogenesis. In particular, nerve growth factor and semaphorin 3A serve as essential functions during and are iteratively used at different stages of tooth innervation. The tooth germ controls development of its own nerve supply, and similar to the development of the tooth organ proper, tissue interactions between dental epithelial and mesenchymal tissues control the establishment of tooth innervation. Tgf-ß, Wnt, and Fgf signaling, which regulate tooth formation, are implicated to mediate these interactions. Therefore, tissue interactions mediated by conserved signal families may constitute key mechanism for the integration of tooth organogenesis and development of its peripheral nerve supply.

Influences of multiple tooth-loss on signal travel in the insular cortex of rats.

The insular cortex (IC) processes various kinds of sensory and emotional information. Multiple tooth-loss induces impairment of oral sensory and motor functions, which might result in the up- or down-regulation of signal processing in the IC. In the present study, we investigated how multiple tooth-loss affects neural activities in the IC. Slices of the IC were prepared from control (untreated) rats and rats raised following the loss of their upper molar teeth, and optical recordings with voltage-sensitive dye were made. Electrical stimulation was delivered to the agranular IC (AIC). The velocity of optical signal from the AIC to the granular IC (GIC) decreased in multiple tooth-loss rats compared with control rats. Field potentials from the GIC were recorded. Onset times of evoked response at the GIC recorded from multiple tooth-loss rats were prolonged compared with those recorded from control rats, suggesting that signal velocity in multiple tooth-loss rats had decreased. A reduced signal velocity was accompanied by neuronal loss in the GIC, which was confirmed by counting the cell numbers on Nissl-stained sections. Thus, multiple tooth-loss may have influences on the GIC where signal processing speed decreases.