Osteonecrosis of the Jaw in Two Rheumatoid Arthritis Patients Not Treated with a Bisphosphonate.

Medication-related osteonecrosis of the jaw (MRONJ) is a side effect in patients taking bone-modifying agents (BMAs), which are highly beneficial for treating osteoporosis and cancer. Bisphosphonates are prescribed to treat secondary osteoporosis in patients with rheumatoid arthritis (RA). We recently encountered two unusual cases of intraoral ONJ in RA patients who had not been treated with a BMA and did not have features of methotrexate- associated lymphoproliferative disorder. Their ONJ stage II bone exposures were treated by conservative therapy, providing good prognoses. These cases indicate that ONJ can occur in RA patients not treated with bisphosphonates. Several risk factors are discussed.

Prognostic Factors for Orthognathic Surgery in Children With Cleft Lip and/or Palate: Dentition and Palatal Morphology.

To determine dental and palatal morphology in children with cleft lip and/or palate (CL/P) and identify morphological prognostic factors for orthognathic surgery (OGS).Retrospective cohort study.Orthodontic department of a university dental hospital.This study included 80 patients with bilateral and unilateral CL/P who had lateral cephalograms at the ages of 7 (T1), 15 (T2) years, and a dental plaster model at T1.Plaster models at T1 were scanned with a three-dimensional (3D) scanner. Morphological features were extracted from 3D models with geometric morphometrics software as principal components (PCs). The combinations of the PCs and other predictive factors (ie, the No. of clefts in the lip and alveolus, the palatal repair method, sex, cephalometric variables at T1, and the No. of missing teeth) were examined by logistic regression to determine the predictability for OGS. The need for OGS and skeletal and dental discrepancies at T2 were examined as outcomes.Shrinkage of the palate, including vertical shallowing and transverse narrowing of the posterior maxilla and cleft-side asymmetry of the anterior maxilla at T1, as well as the No. of clefts in the lip and alveolus, the palatal repair method, male sex, several cephalometric variables for the sagittal and vertical dimensions, and the No. of missing teeth, were found to be predictive factors for OGS.Morphological prognostic factors for OGS in children with CL/P were determined.

Labial Vestibular Flap Closure of the Cleft Palate Is Advantageous for Maxillary Development.

Objective: Using labial vestibular flap was performed to close the primary alveolar and hard palate cleft at the second stage of early 2-stage closure surgery for unilateral cleft lip and palate for minimizing the damage to the maxillary periosteum. We analyzed maxillary development to clarify the influence of cleft palate surgery. Design: Retrospective longitudinal study in 5 years after primary palatal closure. Setting: Institutional study Patients: Study subjects included 214 patients with nonsyndromic complete unilateral cleft lip and palate who were consecutively treated in our clinic. Main Outcome: We used a 3D dental model scanner to assess maxillary development in patients aged 3 months to 5 years after using either the conventional pushback method (PB) (51 cases) or 2-stage closure (Local palatal flap closure: LF [67 cases] and Labial vestibular flap closure: VF [96 cases]). Results: Comparing the measurement results, the major axis of maxilla, width, intercanine distance, and intermolar distance was significantly larger in the LF group compared to the PB group. After the age of 3, the cleft side of VF group had grown significantly to compare with LF group in width. It was also confirmed that the inserted labial mucosal flap itself grew. Enlargement of the labial mucosal flap was observed at all sites except the canine. Conclusion: Good maxillary growth occurred in the following order: VF groups > LF group > PB group. Poor growth was correlated with the extent of periosteal damage during surgery and the degree of postoperative bone surface exposure.

Maxillary Development and Dental Arch Relationships Following Early Two-Stage Palatoplasty: A Comparative Study.

OBJECTIVE: To examine skeletal morphology and dental arch relationships at 8 years of age following early 2-stage palatoplasty, which consists of soft palate plasty at 1 year of age and hard palate closure at 1.5 years of age, and to compare the results with those of conventional pushback palatoplasty. DESIGN: Retrospective. SETTING: Single institutional study. PATIENTS: Eighty-six patients with nonsyndromic complete unilateral cleft lip and palate (UCLP) were selected. INTERVENTION: The subjects were divided into 2 groups according to the palatoplasty protocols, as follows: 45 patients, who underwent early 2-stage palatoplasty (ETS group), and 41 patients, who underwent 1-stage pushback palatoplasty (PB group). MAIN OUTCOME MEASURES: Skeletal morphology was assessed using lateral cephalometric analysis, and dental arch relationships were examined using the GOSLON yardstick. RESULTS: Cephalometric analysis revealed that the anterior-posterior length of the maxilla, measured by PTM-A and PTM-ANS, both projected to the nasal floor (NF) plane, was longer in the ETS group than in the PB group (PTM-A/NF, p = .04; PTM-ANS/NF, p = .03, unpaired t-test), although no significant difference was observed in SNA (p = .09, unpaired t-test). Upper posterior facial height was shorter in the ETS group than in the PB group (p = .02, unpaired t). Assessments with the GOSLON yardstick showed that the ETS group presented better dental arch relationships than the PB group (p = 0.04, Mann-Whitney's U-test). CONCLUSIONS: The present results suggested that the ETS protocol reduced the negative effects of palatal surgery on facial development and dental arch relationships in patients with complete UCLP at 8 years of age.

Indian hedgehog in craniofacial neural crest cells links to skeletal malocclusion by regulating associated cartilage formation and gene expression.

The frontal craniofacial skeleton derived from neural crest cells is vital for facial structure and masticatory functions. The exact role of Indian hedgehog (Ihh) in facial and masticatory development has not been fully explored. In this study, we generated craniofacial neural crest cells-specific Ihh deletion mice (Wnt1-Cre;Ihhfl/fl ;Tomatofl/+ ) and found the gradual dwarfism without perinatal lethality. Morphological and histological analyses revealed unambiguous craniofacial phenotypes in mutants, where we observed skeletal malocclusion accompanied by markedly hypoplastic nasomaxillary complex and reversed incisor occlusion. Both the replacement of nasal concha cartilage by turbinate bones and the endochondral ossification of nasal septum ethmoid bone were substantially delayed. We also observed hypoplastic mandibles in mutants where the mandibular ramus was unexpectedly the most affected. Both the condylar process and mandibular angle cartilages were distorted. However, dental examination showed no significant changes in teeth and dentition. Finally, a comprehensive RNA sequence analysis utilizing condylar cartilage identified Ihh-associated gene network including several cell cycle genes and 16 genes related to the extracellular matrix, sulfate transporters, transcription factors, receptors, a ciliogenesis factor, and an adhesion molecule. Our data provide direct in vivo evidence that Ihh plays crucial roles in midface and masticatory system formation, likely by activating key genes.

Determination of prognostic factors for orthognathic surgery in children with cleft lip and/or palate.

OBJECTIVE: To determine the prognostic factors for orthognathic surgery (OGS) in children with cleft lip and/or palate (CL/P) using artificial intelligence (AI) systems. DESIGN: Retrospective cohort study. SETTING: An orthodontic department at a university dental hospital. PARTICIPANTS: This study included 126 patients with bilateral and unilateral CL/P for whom lateral cephalograms were obtained at three time points: 7 (T1), 10 (T2) and 15 (T3) years of age. MAIN OUTCOME MEASURES: Cleft type, severity of lip separation at birth, number of missing teeth, sex, palatal repair methods and surgeons, cephalometric variables at T1 and T2, and the total duration of orthodontic treatment were examined as predictors. The need for OGS and skeletal and dental discrepancies at T3 was examined as outcomes. RESULTS: A total of six models were developed, with a mean area under the receiver operating characteristic curve of 0.93. Multiple prognostic factors for OGS were identified. In particular, the number of clefts in the lip and alveolus showed relatively high odds ratios, as did anterior crossbite at T3. Achieving palatal closure with the push-back method, rather than Furlow's method, was also found to be a predictive factor for anterior crossbite at T3, with high odds ratios. CONCLUSIONS: The prognostic factors for OGS determined by the AI systems were the number of clefts in the lip and alveolus, the palatal repair method, male sex, several cephalometric variables for the sagittal and vertical dimensions, growth patterns and the number of missing teeth.

Ankyloglossia Superior Syndrome With Complex Craniofacial Anomalies: Case Report and Literature Review.

Ankyloglossia superior syndrome is an extremely rare entity in which centrally located glossopalatine ankylosis is a principal feature. Some cases are accompanied by cleft palate, micrognathia, or tongue hypoplasia, and affected patients need careful nutritional and respiratory support. We describe a newborn girl in whom ankyloglossia superior syndrome comprised complex craniofacial malformations, including cleft palate, micrognathia, microglossia, and natal teeth as well as limb anomalies. Surgical treatment entailed release of synechiae, and glossopexy was performed successfully to prevent postsurgical airway complications and to ensure adequate nutrition by nipple feeding during infancy.

Neuropeptide Y modulates membrane excitability in neonatal rat mesencephalic V neurons.

Neuropeptide Y (NPY) is one of a number of neuropeptides with powerful orexigenic effects. Intracerebroventricular administration of NPY induces increases in food intake and alters feeding rate. Besides it role in feeding behavior, NPY also has significant effects on neuronal systems related to other spontaneous behaviors such as rearing and grooming. In the present study, we examined the direct effects of NPY on mesencephalic V neurons (Mes V), which are important sensory neurons involved in oral motor reflexes and rhythmical jaw movements, as well as masticatory proprioception. Coronal brain slices were prepared from neonatal Sprague-Dawley rats (P3-17) and whole-cell patch clamp recordings were obtained from Mes V neurons. Bath application of NPY depolarized the membrane potential and induced inward current in most neurons. Application of NPY shortened the duration of the afterhyperpolarization following an action potential, and increased the mean spike frequency during repetitive discharge. In those neurons which exhibited rhythmical burst discharge in response to maintained current injection, the bursting frequency was also increased. These effects were mediated predominately by both Y1 and Y5 receptors.

Comparative evaluation of bone microstructure in alveolar cleft repair by cone beam CT: influence of different autologous donor sites and additional application of ß-tricalcium phosphate.

OBJECTIVES: This study used cone beam computed tomography (CBCT) images to comparatively evaluate the three-dimensional microstructural features of reconstructed bone bridge based on the bone harvesting site and the presence/absence of artificial bone material, as well as the features of regenerated bone tissue after bone harvesting from mandibular symphysis in secondary alveolar bone grafting (SABG) for patients with cleft lip, with or without cleft palate. MATERIALS AND METHODS: Thirty-one patients were divided into three groups in which SABG was performed by autologous bone harvesting from iliac crest (IC), mandibular symphysis (MS), or MS combined with ß-TCP granules (MS+TCP). The microstructural trabecular bone parameters (TBPs) and bone structure indexes (SIs) were analyzed using datasets of CBCT images taken before and after SABG. RESULTS: TBPs showed differences between IC and MS groups (P < 0.05), resulting in greater values of bone volume density (P < 0.05) and inferior value of TBPf (P = 0.070) in IC group compared with MS group. Using MS+TCP or filling ß-TCP granules into donor site significantly improved reconstructed or regenerated BV/TV and Tb.Th (P < 0.05) compared with group without ß-TCP. CONCLUSIONS: Microstructural characteristics of reconstructed bone bridge were dependent on the donor site of bone harvesting; using an absorbable bone conductive material improved bone quality and increased bone volume density. CLINICAL RELEVANCE: Application of ß-TCP granules as a partial alternative with autologous bone from mandibular symphysis could obtain comparable outcomes in the microstructure of bone bridge to SABG with autologous iliac crest.

Occlusion at 5 Years of Age Following Hard Palate Closure With Vestibular Flap.

OBJECTIVE: This study aims to assess occlusal relationships and frequency of oronasal fistula at 5 years of age following 2 hard palate closure techniques and to compare results. DESIGN: Retrospective longitudinal study. SETTING: Institutional study. PATIENTS: Study patients included 57 patients with nonsyndromic complete unilateral cleft lip and palate who were consecutively treated. All patients underwent our early 2-stage protocol for palatoplasty, which consisted of soft palate plasty at 1 year of age and hard palate closure at 1.5 years of age. Twenty-nine patients underwent hard palate closure using vestibular flap (VF group) technique (2009-2011) and 28 patients underwent conventional hard palate closure with local palatal flap (LPF group) technique (2006-2008). MAIN OUTCOME MEASURES: Occlusal relationships were assessed with 5-year-olds' index, and frequency of oronasal fistula was investigated. RESULTS: Average 5-year-olds' index scores for VF and LPF groups were 3.11 and 3.57, respectively (P < .001). Oronasal fistula occurred in approximately 7% of patients in the VF group and in 18% of patients in the LPF group. CONCLUSION: Hard palate closure with VF technique may provide better occlusal relationships at 5 years of age than does conventional local closure with the LPF.

Experimentally induced rhythmic jaw muscle activities during non-rapid eye movement sleep in freely moving guinea pigs.

Rhythmic jaw muscle activities frequently occur during non-rapid eye movement sleep in patients with sleep bruxism. The present study aimed to investigate the response characteristics of the masticatory rhythm generation during non-rapid eye movement sleep in animals. Eleven guinea pigs were surgically prepared for polygraphic recordings by electromyography, electrooculography, electroencephalography and electrocardiography with the implantation of a stimulating electrode. Repetitive electrical microstimulations at three intensities were applied to the corticobulbar tract under freely moving conditions. The rhythmic electro-myographic responses of the digastric and masseter muscles were scored and analysed. Changes in cortical electro-encephalographic power and heart rate in association with these stimulations were quantified. Microstimulations to the corticobulbar tract induced rhythmic jaw muscle activities in digastric muscles, occasionally with masseter activities during wakefulness and non-rapid eye movement sleep. The response rate of rhythmic jaw muscle activities was significantly lower (p < 0.01) and the response latency was significantly longer (p < 0.01) during non-rapid eye movement sleep than during wakefulness. At higher stimulus intensities, the response rate increased and response latency decreased. The mean burst intervals of the digastric and masseter muscles were similar regardless of vigilance states and stimulus intensities. Induced rhythmic jaw muscle activities during non-rapid eye movement sleep were followed by a transient decrease in delta power and increases in beta power and heart rate. During non-rapid eye movement sleep, the masticatory motor system is able to generate rhythmic outputs to the jaw muscles in response to facilitatory inputs although the responsiveness was decreased from wakefulness.

Performance status scale for head and neck scores for oral cancer survivors: predictors and factors for improving quality of life.

OBJECTIVES: This study aimed to determine the factors associated with long-term quality of life of oral cancer survivors. MATERIALS AND METHODS: A total of 508 survivors were assessed using the performance status scale for head and neck (PSS-HN), which comprises Eating in Public (E-Public), Normalcy of Diet (N-Diet), and Understandability of Speech (U-Speech). Stepwise multiple linear regression analysis was performed. RESULTS: The median time between the end of treatment and participating in the survey was 38 months (range, 6-250). Overall, 57-60% of survivors achieved full performance (100 score) of each PSS-HN score, whereas 15% had moderate or severe impairment (≤ 50 score) in E-Public and N-Diet, and 4% had impairment in U-Speech. These three scores deteriorated with increasing T-stage. Age, soft tissue reconstruction, trismus, and missing occlusal contacts on the contralateral side were significantly associated with E-Public and N-Diet. Neck dissection, hard tissue reconstruction, and missing occlusal contacts bilaterally were associated with U-Speech score. CONCLUSION: Older age, T4 tumor, and soft tissue reconstruction were predictors of low E-Public and N-Diet performance scores. Increasing mouth opening and maintaining optimal occlusal contacts on the contralateral side may be effective ways to improve N-Diet and E-Public performance. Maintaining optimal occlusal contacts bilaterally may be effective for improving speech performance. CLINICAL RELEVANCE: Oral health care to increase optimal occlusal contacts and rehabilitation of trismus may be promising factors to improve the functional performance of oral cancer survivors.

Orthodontic-Surgical Approach for Treating Skeletal Class III Malocclusion With Severe Maxillary Deficiency in Isolated Cleft Palate.

Orthodontic treatment in patients with orofacial cleft such as cleft lip and palate or isolated cleft palate is challenging, especially when the patients exhibit severe maxillary growth retardation. To correct this deficiency, maxillary expansion and protraction can be performed in the first phase of orthodontic treatment. However, in some cases, the malocclusion cannot be corrected by these procedures, and thus, skeletal discrepancy remains when the patients are adolescents. These remaining problems occasionally require various orthognathic treatments according to the degree of the discrepancy. Here, we describe one case of a female with isolated cleft palate and hand malformation who exhibited severe maxillary deficiency until her adolescence and was treated with multiple orthognathic surgeries, including surgically assisted maxillary expansion (surgically assisted rapid palatal expansion), LeFort I osteotomy, and bilateral sagittal split osteotomy in order to correct severe skeletal discrepancy and malocclusion. The treatment resulted in balanced facial appearance and mutually protected occlusion with good stability. The purpose of this case report is to show the orthodontic treatment outcome of 1 patient who exhibited isolated cleft palate and subsequent severe skeletal deformities and malocclusion which was treated by an orthodontic-surgical approach.

The Elimination of Dental Crowding and Development of a Proper Dental Arch by Maxillary Anterior Segmental Distraction Osteogenesis for a Patient With UCLP.

OBJECTIVE: This report describes the case of a male patient with a complete unilateral cleft lip and palate who presented with midface deficiency and an anteroposteriorly constricted maxilla. DESIGN: Case report Interventions: Correction involved anterior distraction of the segmented maxilla. RESULTS: The present case demonstrates that elongation of the maxilla with anterior distraction is an effective way to develop a proper dental arch, correct anterior and posterior crowding, and improve a midface deficiency.

Efficacy of Maxillary Anterior Segmental Distraction Osteogenesis in Patients With Cleft Lip and Palate.

OBJECTIVES: To evaluate the effects of maxillary anterior segmental distraction osteogenesis (MASDO) in patients with cleft lip and palate (CLP) and to identify risk factors for increased relapse. DESIGN: A retrospective study. PATIENTS: Thirty-one Japanese patients with CLP who underwent MASDO were eligible for study inclusion. MAIN OUTCOME MEASURES: We evaluated lateral cephalograms obtained before (T1), at 3 months (T2), and at 1 year (T3) after MASDO, and measured changes from T1 to T2 (δT1T2), from T2 to T3 (δT2T3), and from T1 to T3 (δT1T3). We also evaluated the risk factors associated with an increased relapse. RESULTS: Overall (δT1T3), MASDO improved retrusion of the maxilla. We measured a significant advancement (6.1 mm) of the anterior maxillary segment in δT1T2 (A-McNamara classification) and increases in the overjet and the SNA, ANB, and nasolabial angles. However, skeletal relapse was evident in δT2T3, and the median percentage of relapse was 10%. To explore the risk factors, we subdivided patients with a δT1T2 of >5 mm into 2 groups based on the percentage of relapse (>15% vs ≤15%). There were significant differences between these groups in the vertical positions of the anterior nasal spine and point A, and the angle formed by the SN and palatal planes (SNPP), suggestive of intraoperative counterclockwise rotation of the maxilla. CONCLUSIONS: MASDO is effective for correcting midfacial deficiencies, but counterclockwise rotation of the maxilla during surgery may cause relapse.

Extracellular Phosphate Induces the Expression of Dentin Matrix Protein 1 Through the FGF Receptor in Osteoblasts.

Dentin matrix protein 1 (Dmp1) is an extracellular matrix protein involved in phosphate metabolism and biomineralization, and its expression markedly increases during the maturation of osteoblasts into osteocytes. We previously reported that an increased level of inorganic phosphate (Pi) in media up-regulated the expression of Dmp1 in primary osteocytes isolated from mouse bones. In the present study, we found that elevated extracellular Pi strongly induced the expression of Dmp1 in osteoblasts and explored its underlying mechanism of action. In an osteoblastic cell line MC3T3-E1, increases in extracellular Pi induced the phosphorylation of ERK1/2 and up-regulated the expression of Dmp1, fibroblast growth factor 2 (Fgf2), and Fgf receptor 1 (Fgfr1). A co-treatment with the MEK inhibitor U0126 abolished the increase in the expression of Dmp1 and Fgfr1 by elevated Pi, suggesting the involvement of the MEK/ERK pathway in this up-regulation. Elevated extracellular Pi also resulted in the phosphorylation of FGF receptor substrate 2α (FRS2α), which was diminished by knockdown of Slc20a1 encoding Pit1 sodium-phosphate co-transporter. The co-treatment with an inhibitor against FGFR (SU5402) abolished the up-regulation of Dmp1 induced by elevated extracellular Pi. In primary osteoblasts, a treatment with 4 mM Pi transiently increased the expression of early growth response 1 (Egr1) before the up-regulation of Dmp1. These results indicate that FGFR mediates the direct effects of extracellular Pi on the expression of Dmp1 in osteoblasts and enhance the close relationship between the signaling evoked by elevated extracellular Pi and FGF/FGFR signaling. J. Cell. Biochem. 118: 1151-1163, 2017. © 2016 Wiley Periodicals, Inc.

Cephalometric Outcomes of Maxillary Expansion and Protraction in Patients With Unilateral Cleft Lip and Palate After Two Types of Palatoplasty.

OBJECTIVE: To clarify the differences in the long-term effects of maxillary expansion (ME) and protraction (MP) in patients with complete unilateral cleft lip, alveolus, and palate (UCLP) undergoing two types of palatoplasty. DESIGN: Retrospective longitudinal study. SETTING: Institutional study. PATIENTS AND INTERVENTIONS: Thirty-eight patients with UCLP treated at Osaka University Dental Hospital, Japan, were divided into two groups: 19 patients were treated using Wardill-Kilner push-back palatoplasty (PB), and 19 patients were treated with early two-stage palatoplasty according to the modified Furlow technique (ETS). All patients exhibited a short maxilla at the initial orthodontic visit and were treated with ME using a quad helix appliance and MP with a face mask. Lateral cephalometric data recorded in the initial stage were compared with those obtained at the end of treatment. MAIN OUTCOME MEASUREMENTS: The dentoskeletal features and facial soft tissue profile were evaluated before and after orthodontic treatment. The variation and rate of change during treatment were also calculated. The Mann-Whitney U test was used for the statistical analyses. RESULTS: The ETS group showed significantly greater SNA, SNB, and U1-Pp angles and smaller SN-Mp angles than the PB group after face mask treatment. The variation in the anteroposterior length of the maxilla during treatment was significantly greater in the ETS group than in the PB group. CONCLUSIONS: Maxillary protraction was more efficiently accomplished in the patients with UCLP after early two-stage palatoplasty compared with push-back palatoplasty.

Influence of Different Palatoplasties on the Facial Morphology of Early Mixed Dentition Stage Children With Unilateral Cleft Lip and Palate.

OBJECTIVE: To compare the maxillofacial morphology in the early mixed dentition phase between two patient groups with unilateral cleft lip, alveolus, and palate who underwent different types of palatoplasty. DESIGN: Cross-sectional study. SETTING: An institutional study. PATIENTS AND INTERVENTIONS: Seventy-one patients with unilateral cleft lip and palate (UCLP) treated at Osaka University Dental Hospital, Japan, were divided into two groups: 33 patients were treated by early two-stage palatoplasty by the modified Furlow Technique (ETS), and 38 patients were treated by one-stage Wardill-Kilner push-back palatoplasty (PB). Intergroup comparisons were performed. MAIN OUTCOME MEASURES: The dental, skeletal, and soft-tissue features were evaluated. For intergroup comparisons, Mann-Whitney U test was used for the statistical analyses. RESULTS: No significant differences existed between the ETS and PB groups regarding the skeletal features except for the mandibular ridge height. Meanwhile, the upper central incisor and upper lip of the ETS group showed a more anterior position than those in the PB group. CONCLUSIONS: Early two-stage Furlow palatoplasty leads to more protruded upper lip, providing more anteriorly positioned upper incisors compared with PB, at least at the early mixed dentition stage.

Asymmetric Anterior Distraction for Transversely Distorted Maxilla and Midfacial Anteroposterior Deficiency in a Patient With Cleft Lip/Palate: Two-Stage Surgical Approach.

The present report describes a male patient with a unilateral cleft lip and palate who presented with midfacial anteroposterior and transverse deficiency. Correction involved a two-stage surgical-orthodontic approach: asymmetric anterior distraction of the segmented maxilla followed by two-jaw surgery (LeFort I and bilateral sagittal splitting ramus osteotomies). The present case demonstrates that the asymmetric elongation of the maxilla with anterior distraction is an effective way to correct a transversely distorted alveolar form and midfacial anteroposterior deficiency. Furthermore, successful tooth movement was demonstrated in the new bone created by distraction.

Generation of resonance-dependent oscillation by mGluR-I activation switches single spiking to bursting in mesencephalic trigeminal sensory neurons.

The primary sensory neurons supplying muscle spindles of jaw-closing muscles are unique in that they have their somata in the mesencephalic trigeminal nucleus (MTN) in the brainstem, thereby receiving various synaptic inputs. MTN neurons display bursting upon activation of glutamatergic synaptic inputs while they faithfully relay respective impulses arising from peripheral sensory organs. The persistent sodium current (IN aP ) is reported to be responsible for both the generation of bursts and the relay of impulses. We addressed how IN aP is controlled either to trigger bursts or to relay respective impulses as single spikes in MTN neurons. Protein kinase C (PKC) activation enhanced IN aP only at low voltages. Spike generation was facilitated by PKC activation at membrane potentials more depolarized than the resting potential. By injection of a ramp current pulse, a burst of spikes was triggered from a depolarized membrane potential whereas its instantaneous spike frequency remained almost constant despite the ramp increases in the current intensity beyond the threshold. A puff application of glutamate preceding the ramp pulse lowered the threshold for evoking bursts by ramp pulses while chelerythrine abolished such effects of glutamate. Dihydroxyphenylglycine, an agonist of mGluR1/5, also caused similar effects, and increased both the frequency and impedance of membrane resonance. Immunohistochemistry revealed that glutamatergic synapses are made onto the stem axons, and that mGluR1/5 and Nav1.6 are co-localized in the stem axon. Taken together, glutamatergic synaptic inputs onto the stem axon may be able to switch the relaying to the bursting mode.