Analysis of perioperative autonomic nervous system activity to visualize stress in pediatric patients undergoing alveolar bone graft surgery.

Perioperative stress in pediatric patients is often difficult to assess via interviews; thus, an objective measure to assess perioperative stress is needed. To visualize perioperative stress, we observed autonomic nervous system (ANS) activity, circulatory dynamics, and psychological status in pediatric patients undergoing alveolar bone grafting under general anesthesia. This prospective observational study included 40 patients aged 8-12 years who were scheduled for alveolar bone grafting in our hospital. ANS activity was analyzed using heart rate variability the day before surgery, during general anesthesia, 2 h postoperatively, 24 h postoperatively, and the day before discharge. ANS assessment included LF/HF (sympathetic nervous system activity) and HF (parasympathetic nervous system activity). Additionally, heart rate (HR), systolic blood pressure (SBP), face scale (FS) score were recorded. Data from 31 patients, excluding dropouts, were analyzed. The ratio of change to the preoperative value was compared. After surgery, the LF/HF, HR, SBP, and FS score significantly increased (P < 0.01) and HF significantly decreased (2 h postoperatively: P < 0.05, 24 h postoperatively, before discharge: P < 0.01). SBP recovered to preoperative values 24 h postoperatively, and HR and FS scores recovered to preoperative values before discharge. However, even before discharge, LF/HF remained significantly higher than preoperative values, and HF remained significantly lower than preoperative values (P < 0.01). Conclusion We observed perioperative stress from multiple perspectives. Circulatory dynamics and psychological status recovered by the day before discharge; however, ANS activity did not. Therefore, evaluating ANS activity may be useful in visualizing potential perioperative stress in pediatric patients.

Estimation of the Risk of Postoperative Hypertension Following Minor to Moderate Surgery Using an Echocardiogram and Biomarkers.

This study aimed to determine independent factors for developing postoperative hypertension using 4 biomarkers in patients receiving oral and maxillofacial surgery under general anesthesia. Brain natriuretic peptide (BNP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity myocardial troponin T (hs-TnT), and high-sensitivity myocardial troponin I (hs-TnI) were measured and preoperative echocardiograms were examined. Episodes of systolic blood pressure (SBP) ≥ 170 mmHg or diastolic blood pressure ≥ 100 mmHg within 1 week after surgery were considered postoperative hypertension. We analyzed 213 (130 men; 83 women) patients, who were divided into a postoperative hypertension group (HT group, n = 32) and a normal group (N group, n = 181). The HT group showed a higher LVMI (113.5 versus 100.1), higher E/e' of the lateral wall (9.1 versus 7.7), and higher BNP (39.2 versus 22.9 pg/mL), NT-proBNP (400.1 versus 143.9 pg/mL), and hs-TnT (15.6 versus 10.3 ng/L) concentrations compared to the N group. NT-proBNP and hs-TnT concentrations positively associated with E/e', but BNP and hs-TnI did not. NT-proBNP (AUC = 0.64, cutoff value: 117.0 pg/mL) and hs-TnT (AUC = 0.61, cutoff value: 11.0 ng/L) concentrations were effective for discriminating E/e' ≥ 12. Multivariate logistic regression analyses showed that risk factors responsible for developing postoperative hypertension were NT-proBNP and hs-TnT using biomarkers and E/e' as independent variables, and NT-proBNP and SBP at admission using biomarkers and SBP at admission as independent variables. These findings suggest that NT-proBNP and hs-TnT concentrations, and SBP at admission, are useful to predict postoperative hypertension after minor to moderate surgery, and that left ventricular filling pressure is a primary factor associated with postoperative hypertension.

Linalool odor-induced analgesia is triggered by TRPA1-independent pathway in mice.

We had recently reported that linalool odor exposure induced significant analgesic effects in mice and that the effects were disappeared in olfactory-deprived mice in which the olfactory epithelium was damaged, thus indicating that the effects were triggered by chemical senses evoked by linalool odor exposure. However, the peripheral neuronal mechanisms, including linalool receptors that contribute toward triggering the linalool odor-induced analgesia, still remain unexplored. In vitro studies have shown that the transient receptor potential ankyrin 1 (TRPA1) responded to linalool, thus raising the possibility that TRPA1 expressed on the trigeminal nerve terminal detects linalool odor inhaled into the nostril and triggers the analgesic effects. To address this hypothesis, we measured the behavioral pain threshold for noxious mechanical stimulation in TRPA1-deficient mice. In contrast to our expectation, we found a significant increase in the threshold after linalool odor exposure in TRPA1-deficient mice, indicating the analgesic effects of linalool odor even in TRPA1-deficient mice. Furthermore, intranasal application of TRPA1 selective antagonist did not alter the analgesic effect of linalool odor. These results showed that the linalool odor-induced analgesia was triggered by a TRPA1-independent pathway in mice.

Sympathetic Nerve Activity During Tooth Extraction in Women Is Related to Dental Anxiety Immediately After Surgery.

PURPOSE: This study assessed the relationship between changes in autonomic nervous system activity during impacted mandibular third molar extraction and a patient's postoperative psychological status, with the overarching aim of informing the development of interventions to reduce dental phobia and anxiety. We hypothesized that changes in autonomic nervous system activity during tooth extraction are related to postoperative psychology. METHODS: In our prospective cohort study, heart rate variability, heart rate (HR), and systolic blood pressure (SBP) were recorded during impacted mandibular third molar extraction. Heart rate variability values were dichotomized as either low frequency (LF 0.04-0.15 Hz) or high frequency (HF >0.15 Hz). The relative ratios (intraoperative vs baseline) of LF/HF, HF, HR, and SBP were divided into high and low groups based on their median values; the State Anxiety Inventory (STAI-S) results were compared between the groups with high and low relative ratios. RESULTS: Data of 34 female patients (age, 28.23 ± 1.05 years) were analyzed. Postoperative STAI-S values were significantly lower than preoperative values. Patients in the high LF/HF group had a significantly lower change in STAI-S values than those in the low LF/HF group (P < .05). There were no significant differences in the change in STAI-S values between the groups with high and low HF, HR, or SBP. CONCLUSIONS: Patients with low sympathetic nervous system activity had lower anxiety; the LF/HF index was the most sensitive indicator for changes in stress. Additional studies are required to develop optimal interventions for reducing sympathetic nerve activity in patients with dental phobia.

Difference in the Effects of Lidocaine With Epinephrine and Prilocaine With Felypressin on the Autonomic Nervous System During Extraction of the Impacted Mandibular Third Molar: A Randomized Controlled Trial.

PURPOSE: Complications during local anesthesia include increased blood pressure and vasovagal reflex, which are caused by changes in the autonomic nervous system. The commonly used local anesthetic preparations are lidocaine to which the vasoconstrictor epinephrine is added (lidocaine-epinephrine) and prilocaine to which the vasoconstrictor felypressin is added (prilocaine-felypressin); however, their effects during dental treatment are unclear. We examined the effects of these 2 different local anesthetic preparations on the autonomic nervous system and circulation during extraction of the impacted mandibular third molar. MATERIALS AND METHODS: In this randomized controlled trial, 40 female patients scheduled for extraction of an impacted mandibular third molar were randomized to the lidocaine-epinephrine group or prilocaine-felypressin group. Heart rate variability, heart rate, and systolic blood pressure were recorded during the experiment. Descriptive and bivariate statistics were computed, and the P value was set at .05. RESULTS: The low frequency-high frequency ratio was significantly increased in the prilocaine-felypressin group during extraction compared with that in the lidocaine-epinephrine group (P < .05). In the lidocaine-epinephrine group, a significant decrease in the high-frequency component was observed during bone removal and extraction compared with that at rest (P < .05). In both groups, a significant increase in systolic blood pressure was observed during local anesthesia, incision and reflection of the flap, bone removal, separation of the tooth crown, extraction, and suturing compared with that at rest (P < .01). CONCLUSIONS: This study is the first to investigate the differences in the influence of 2 different local anesthetic preparations on the autonomic nervous system during extraction of the mandibular third molar. Changes in circulatory dynamics during tooth extraction with the 2 different local anesthetic preparations were the result of a decrease in parasympathetic nervous activity with lidocaine-epinephrine and an increase in sympathetic nervous activity with prilocaine-felypressin.

The State Anxiety Inventory Is Useful for Predicting the Autonomic Nervous System State of Patients Before the Extraction of an Impacted Mandibular Third Molar.

PURPOSE: Dental anxiety about extraction of impacted mandibular third molars changes the activity of the autonomic nervous system. Thus, to provide safe dental treatment, it is important that a surgeon be aware of a patient's pretreatment anxiety and autonomic nervous system state. Therefore, we analyzed how a scheduled treatment to extract mandibular third molars affects the pretreatment electroencephalogram (EEG), autonomic nervous system, and psychological state of patients. We compared their findings with those of volunteers not scheduled to undergo dental treatment. PATIENTS AND METHODS: The study enrolled 30 patients who were scheduled to undergo impacted mandibular third molar extraction (ie, pretreatment group) and 30 volunteers who were not (ie, control group). Heart rate variability and an EEG were recorded during the experiment. The State Anxiety Inventory-State Anxiety scale (STAI-S) scores were recorded before the procedure. For the statistical analysis, P < .05 was deemed statistically significant. RESULTS: High-frequency (HF) variability was significantly decreased and the STAI-S score was significantly increased in the pretreatment group compared with the control group (P < .01 for both). The low frequency (LF)/HF ratio and alpha-wave activity showed a significant negative correlation on both sides in the control group (P < .01); however, no correlation existed in the pretreatment group. The LF/HF ratio and STAI-S score showed a significant positive correlation in the pretreatment group (P < .05); however, no correlation existed in the control group. CONCLUSIONS: Predicting a patient's autonomic nervous system state before dental treatment based on the EEG was difficult. The STAI-S psychological test was a useful method.

The Effects of Music Listening During Extraction of the Impacted Mandibular Third Molar on the Autonomic Nervous System and Psychological State.

PURPOSE: Pain, anxiety, and nervousness related to dental procedures can cause acute changes in the autonomic nervous system. Music is widely accepted as a relaxation method during dental treatment; however, its effects during dental treatment are unclear. The authors explored the effects of listening to music during extraction of the impacted mandibular third molar on the autonomic nervous system and the psychological state and hypothesized that listening to music would suppress sympathetic nervous activity and decrease anxiety. MATERIALS AND METHODS: In this prospective study, 40 patients scheduled for extraction of an impacted mandibular third molar were randomized into 2 groups: extraction without music (control group) and extraction while listening to music (music group). Heart rate variability was recorded during the experiment, and Modified Dental Anxiety Scale and State-Trait Anxiety Inventory (STAI) scores were recorded before and after the procedure. Descriptive and bivariate statistics were computed and the P value was set at .05. RESULTS: An increased low-to-high frequency ratio was observed in the control group during incision and flap reflection, bone removal, and separation of the tooth crown; the ratio was significantly decreased in the music group during these time points (P < .05). Compared with the control group, the music group had a significantly greater decrease in postoperative STAI State Anxiety scores from preoperative levels (P < .05). CONCLUSIONS: This study suggested that listening to music while undergoing extraction of the impacted mandibular third molar suppresses activity of the sympathetic nerves during incision, flap reflection, bone removal, and separation of the tooth crown and relieves anxiety after treatment. Future studies will focus on the mechanisms involved and methods to prevent the onset of systemic incidents.

Predictive Factors of Postoperative Blood Pressure Abnormalities Following a Minor-to-Moderate Surgery.

Myocardial ischemic events after non-cardiac surgery is still a serious problem, especially in older, high-risk patients. However, the prevalence and risk factors of blood pressure (BP) abnormalities, which may possibly lead to myocardial ischemic attack, have not been reported. Our aim is to elucidate predictive factors of postoperative BP abnormalities following a minor-to-moderate surgery, employing preoperative left ventricular diastolic function. Patients who underwent cardiac echocardiogram examination and received oral and maxillofacial surgery under general anesthesia were enrolled. The echocardiographic parameters of diastolic function were compared between patients who had postoperative BP abnormalities (hypertension-systolic blood pressure [SBP] ≥ 170 mmHg-or hypotension-SBP < 80 mmHg-episode) that required therapeutic interventions until 7 days after surgery and those who had no BP abnormalities. Of the 173 patients analyzed, 25 (14.4%) had BP abnormalities. BP abnormalities patients were older, having a larger proportion of diabetes mellitus, lower E/A ratio and e', and larger E/e' and left atrial dimension than those without BP abnormalities. Subanalyses revealed that the independent risk factors responsible for hypertension episodes (14 patients) were the mean e' (odd ratio [OR]: 0.434; 95% confidence interval [CI]: 0.229-0.824), diabetes mellitus (OR: 5.018; 95% CI: 1.030-24.436), SBP at hospitalization (OR: 1.099; 95% CI: 1.036-1.165), and operation time (hour; OR: 1.326; 95%CI: 1.109-1.586), while hypotension episodes (11 patients) were associated solely with operation time (OR: 1.206; 95% CI: 1.046-1.391). In conclusion, left ventricular diastolic dysfunction, increased insulin resistance, boosted SBP at hospitalization, and prolonged operation should be taken into consideration as risk factors of postoperative BP abnormalities, especially hypertension, following minor-to-moderate surgery.

Recovery of Endothelial Function after Minor-to-Moderate Surgery Is Impaired by Diabetes Mellitus, Obesity, Hyperuricemia and Sevoflurane-Based Anesthesia.

Endothelial dysfunction is observed in several cardiovascular diseases, where endothelium-dependent vasodilation is impaired by oxidative stress. However, the time course of endothelial function during the perioperative period of a minor-to-moderate surgery, and the effects of atherosclerotic risk factors and employed general anesthetics on recovery of endothelial function, are unknown. Endothelial function of 30 patients was evaluated as the reactive hyperemia index (RHI) of reactive hyperemia peripheral arterial tonometry. RHI was measured on day before surgery (control), immediately after surgery (Day 0), day after surgery (Day 1), and day 4 after surgery (Day 4) in patients with no functional limitations who were scheduled for oral and maxillofacial surgery of around 3 hours. Sevoflurane- or propofol-based anesthesia supplemented with an opioid analgesic remifentanil was employed. The control RHI was 2.26 ± 0.64. The RHI significantly decreased to the lowest level on Day 0 (1.52 ± 0.28), recovered on Day 1 (2.07 ± 0.58), and improved further on Day 4 (2.55 ± 0.83). Multiple linear regression analysis revealed that recovery of the RHI from Day 0 to Day 4 was impaired by diabetes mellitus (P = 0.0313), obesity (BMI ≥ 25; P = 0.0166), hyperuricemia (uric acid ≥ 6.0 mg/dL; P = 0.0416) and sevoflurane-based anesthesia (P = 0.0308). These findings suggest that endothelial function as evaluated by the RHI is severely suppressed on the day of a minor-to-moderate surgery, and that it improves until the 4th postoperative day on average. Recovery of endothelial function is impaired by diabetes mellitus, obesity, hyperuricemia, and sevoflurane-based anesthesia.

Trigeminal nervous system sensitization by infraorbital nerve injury enhances responses in a migraine model.

Background Although the peripheral and central sensitizations of trigeminal nervous system may be one of the important factors of migraine, the precise mechanism is not fully understood. In this study, we examined the influence of the sensitization of the second division of the trigeminal nerve (V2) by chronic constriction injury (CCI) of the infraorbital nerve (ION) on migraine headache, using the capsaicin-induced migraine model. Methods Male Sprague-Dawley rats were assigned to four groups: (a) sham surgery and topical-dural vehicle application (Sham + Vehicle) group, (b) CCI-ION and topical-dural vehicle application (CCI-ION + Vehicle) group, (c) sham surgery and topical-dural capsaicin application (Sham + Capsaicin) group, (d) CCI-ION and topical-dural capsaicin application (CCI-ION + Capsaicin) group. Behavioral testing and immunohistochemical staining were performed. Results In the behavioral test, the Sham + Capsaicin group showed significantly longer duration of immobilization and shorter duration of exploration compared with the Sham + Vehicle group, which is similar to clinical features of migraine patients. Moreover, CCI-ION enhanced these effects in the CCI-ION + Capsaicin group. Immunohistochemical staining for phospho-extracellular signal-related kinase (pERK) in the trigeminal ganglion (TG) containing first and second divisions of the trigeminal nerve and the trigeminocervical complex (TCC) revealed that pERK expression was significantly increased in the CCI-ION + Capsaicin group compared with the other groups. However, comparing between effects of the peripheral and central sensitizations (in the TG and TCC), from our results, peripheral sensitization would play a much less or not significant role. Conclusions These data demonstrate that the sensitization of V2 could influence the activation and the sensitization of the first division of the trigeminal nerve in the TCC, subsequently exacerbating pain sensation and pain-related behaviors. We have shown for the first time that the existence of the central sensitization of V2 can be an exacerbating factor for migraine related nociceptive thresholds/activation.

Effective Dosage of Midazolam to Erase the Memory of Vascular Pain During Propofol Administration.

Intravenous sedation with propofol is often administered to anxious patients in dental practice. Pain on injection of propofol is a common adverse effect. This study aimed to determine the age-adjusted doses of midazolam required to erase memory of vascular pain of propofol administration and assess whether the Ramsay Sedation Scale (RSS) after the pretreatment of midazolam was useful to predict amnesia of the vascular pain of propofol administration. A total of 246 patients with dental phobia requiring dental treatment under intravenous sedation were included. Patients were classified according to their age: 30s, 40s, 50s, and 60s. Three minutes after administration of a predetermined dose of midazolam, propofol was infused continuously. After completion of the dental procedure, patients were interviewed about the memory of any pain or discomfort in the injection site or forearm. The dosage of midazolam was determined using the Dixon up-down method. The first patient was administered 0.03 mg/kg, and if memory of vascular pain remained, the dosage was increased by 0.01 mg/kg for the next patient, and then if the memory was erased, the dosage was decreased by 0.01 mg/kg. The effective dosage of midazolam in 95% of each age group for erasing the memory of propofol vascular pain (ED95) was determined using logistic analysis. The accuracy of RSS to predict the amnesia of injection pain was assessed by receiver operating characteristic (ROC) analysis. The ED95 of midazolam to erase the memory of propofol vascular pain was 0.061 mg/kg in patients in their 30s, 0.049 mg/kg in patients in their 40s, 0.033 mg/kg in patients in their 50s, and 0.033 mg/kg in patients in their 60s. The area under the ROC curve was 0.31. The ED95 of midazolam required to erase the memory of propofol vascular pain demonstrated a downward trend with age. On the other hand, it was impossible to predict the amnesia of propofol vascular pain using the RSS.

Appropriate sevoflurane concentration to stabilize autonomic activity during intubation with rocuronium in infants: a randomized controlled trial.

BACKGROUND: In infants, sevoflurane is commonly used for induction of anesthesia, following which a muscle relaxant is administered to facilitate tracheal intubation. When rocuronium is used as the muscle relaxant, intubation may be performed before reaching an adequate depth of anesthesia because of its rapid onset. The purpose of this study was to investigate the optimal sevoflurane concentration that would minimize the impact of intubation on hemodynamics and autonomic nervous system (ANS) activity in infants. METHODS: Sixty-one infants aged 1-6 months, undergoing cleft lip repair, were enrolled. Patients were randomly assigned to three end-tidal sevoflurane concentration (E'Sevo) groups, 3%, 4% and 5%. Anesthesia was induced with 5% sevoflurane with 100% oxygen, and rocuronium (0.6 mg/kg) was administered. The concentration of sevoflurane was adjusted to the predetermined concentration in each group. Mechanical pressure control ventilation via a face mask was commenced. Five minutes after E'Sevo became stable at the predetermined concentration, tracheal intubation was performed. Immediately after tracheal intubation, ventilation was restarted at the same ventilator settings and continued for 150 seconds. Heart rate (HR) and mean arterial pressure (MAP) were measured 5 times in the 150 seconds after intubation. Normalized units (nu) of high frequency (HF: 0.04-0.15 Hz) and the ratio of low frequency (LF: 0.15-0.4 Hz) to HF components (LF/HF) of HR variability were calculated by MemCalc/Tonam2C™. Normalized units of HF (HFnu) and LF/HF reflect cardiac parasympathetic and sympathetic activity, respectively. RESULTS: After intubation, HR increased slightly in all groups and MAP increased by 9.2% in the E'Sevo-3% group. LF/HF increased (p < 0.01) and HFnu decreased (p < 0.01) in all groups 30 seconds after intubation. HFnu was lower (p < 0.001) and LF/HF was higher (p = 0.007) in the E'Sevo-3% group than in E'Sevo-5% group. ANS responses to intubation were reduced in a dose-dependent manner. CONCLUSIONS: Sympathomimetic and parasympatholytic responses to intubation in the E'Sevo-3% group were much greater than those in the E'Sevo-5% group. During tracheal intubation in infants, 4% or 5% sevoflurane is appropriate for prevention of sympathetic hyperactivation and maintenance of ANS balance as compared to 3% sevoflurane, when a muscle relaxant is co-administered. TRIAL REGISTRATION: The study was registered at UMIN-CTR ( UMIN000009933).

A prospective, randomized controlled trial of conscious sedation using propofol combined with inhaled nitrous oxide for dental treatment.

PURPOSE: Adverse reactions during propofol sedation include a decrease in arterial blood pressure, propofol-induced pain on injection, and airway complications. The purpose of this study was to investigate whether combined use of intravenous propofol and inhaled nitrous oxide could decrease the hypotensive and other adverse effects of propofol. PATIENTS AND METHODS: We designed and implemented a prospective, randomized controlled trial. Patients undergoing dental procedures requiring intravenous sedation were randomly allocated to 2 groups: group P comprised those receiving sedation with propofol alone, and group N+P comprised those receiving sedation with 40% nitrous oxide inhalation and propofol. During the dental procedures, the sedation level was maintained at an Observer's Assessment of Alertness/Sedation scale score of 4 by adjusting propofol's target plasma concentration. Nitrous oxide inhalation was the predictor variable, whereas the hemodynamic changes, amount and concentration of propofol, and adverse events were the outcome variables. RESULTS: Eighty-eight patients were successfully analyzed without any complications. The total amount of propofol was significantly less in group N+P (249.8 ± 121.7 mg) than in group P (310.3 ± 122.4 mg) (P = .022), and the mean concentration of propofol was significantly less in group N+P (1.81 ± 0.34 µg/mL) than in group P (2.05 ± 0.44 µg/mL) (P = .006). The mean blood pressure reduction in group N+P (11.0 ± 8.0 mm Hg) was significantly smaller than that in group P (15.8 ± 10.2 mm Hg) (P = .034). Pain associated with the propofol injection and memory of the procedure were less in group N+P (P = .011 and P = .048, respectively). Nitrous oxide did not affect respiratory conditions or recovery characteristics. CONCLUSIONS: The results of this study suggest that nitrous oxide inhalation combined with propofol sedation attenuates the hypotensive effect and pain associated with propofol injections, along with potentiating the amnesic effect.

Considerations during intravenous sedation in geriatric dental patients with dementia.

OBJECTIVES: We retrospectively assessed the usability and precautions required during intravenous sedation (IVS) for dental treatment in geriatric outpatients with dementia. MATERIALS AND METHODS: We investigated the intraoperative complications in 65 cases (25 geriatric dental patients with dementia) under IVS, from the standpoint of local anesthesia usage, water usage during treatment, and content of treatment. RESULTS: Circulatory complications occurred in 46.2 % and respiratory complications in 52.3 % of all cases (n = 65). Bradycardia occurred in 13.8 % and hypotension in 12.3 % of cases in the former, while coughing spells occurred in 41.5 % and snoring in 16.9 % of cases in the latter. Many of the local anesthesia usage cases did not require water usage, such as during tooth extraction (p < 0.0001). Water usage cases, such as for caries treatment, needed longer sedation and treatment times, resulting in more propofol usage (p < 0.001, p < 0.0001, and p < 0.01, respectively). Many coughing spells developed in the water usage cases (p < 0.05). 81.8 % of snoring and 63.3 % of circulatory complications, such as hypotension and bradycardia, developed in the tooth extraction cases (p < 0.05). CONCLUSIONS: All the scheduled dental treatments in dementia patients were smoothly performed under IVS. However, stringent attention should be paid to the prevention of aspiration of fluids retained in the pharynx, airway obstruction due to therapeutic maneuvers, respiratory inhibition by sedatives, and hemodynamic fluctuations caused by invasive procedures under local anesthesia. CLINICAL RELEVANCE: In the future, with the growing need for dental procedures in dementia patients, dentists will require training in the general management of such patients.

Three-dimensional topography of rat trigeminal ganglion neurons using a combination of retrograde labeling and tissue-clearing techniques.

The trigeminal nerve is the sensory afferent of the orofacial regions and divided into three major branches. Cell bodies of the trigeminal nerve lie in the trigeminal ganglion and are surrounded by satellite cells. There is a close interaction between ganglion cells via satellite cells, but the function is not fully understood. In the present study, we clarified the ganglion cells' three-dimensional (3D) localization, which is essential to understand the functions of cell-cell interactions in the trigeminal ganglion. Fast blue was injected into 12 sites of the rat orofacial regions, and ganglion cells were retrogradely labeled. The labeled trigeminal ganglia were cleared by modified 3DISCO, imaged with confocal laser-scanning microscopy, and reconstructed in 3D. Histograms of the major axes of the fast blue-positive somata revealed that the peak major axes of the cells innervating the skin/mucosa were smaller than those of cells innervating the deep structures. Ganglion cells innervating the ophthalmic, maxillary, and mandibular divisions were distributed in the anterodorsal, central, and posterolateral portions of the trigeminal ganglion, respectively, with considerable overlap in the border region. The intermingling in the distribution of ganglion cells within each division was also high, in particular, within the mandibular division. Specifically, intermingling was observed in combinations of tongue and masseter/temporal muscles, maxillary/mandibular molars and masseter/temporal muscles, and tongue and mandibular molars. Double retrograde labeling confirmed that some ganglion cells innervating these combinations were closely apposed. Our data provide essential information for understanding the function of ganglion cell-cell interactions via satellite cells.

Cough reflex under intravenous sedation during dental implant surgery is more frequent during procedures in the maxillary anterior region.

PURPOSE: The present study was performed to evaluate the incidence of cough episodes and the association between cough episodes and patient-related and site-specific parameters during implant surgery when performed under intravenous sedation. MATERIALS AND METHODS: One hundred forty-seven patients scheduled for dental implant surgeries under intravenous sedation were enrolled in this study. Heart rate, blood pressure, percutaneous oxygen saturation, and bispectral index were monitored. Sedation was induced intravenously by a bolus administration of midazolam and maintained by a continuous administration of propofol. Sedation level was adjusted to achieve scores of 3 to 4 on the Ramsay Sedation Scale. Surgical procedures were divided into 11 stages. Implant sites were labeled as right maxillary molar, maxillary anterior, left maxillary molar, right mandibular molar, mandibular anterior, and left mandibular molar sites. When coughing occurred, heart rate, blood pressure, percutaneous oxygen saturation, bispectral index, procedure being performed, and surgical site being stimulated were recorded. RESULTS: One hundred seventy-two cough episodes were observed in 97 patients (66%). Cough episodes occurred during all stages of surgery but were substantially more frequent during preparation of the implant site. The incidence of cough episodes was significantly higher at the maxillary anterior site and lowest at the right mandibular molar areas. CONCLUSION: These findings suggest that difficulties in swallowing and in the suction of intraoral fluids have variable effects at different surgical sites. Careful suction of intraoral water and an appropriate sedation level are required, especially in procedures in the maxillary anterior region.

Kamishoyosan and Kamikihito protect against decreased KCC2 expression induced by the P. gingivalis lipopolysaccharide treatment in PC-12 cells and improve behavioral abnormalities in male mice.

Kamishoyosan (KSS) and Kamikihito (KKT) have been traditionally prescribed for neuropsychiatric symptoms in Japan. However, the molecular mechanism of its effect is not elucidated enough. On the other hand, it has been reported that lipopolysaccharide derived from Porphyromonas gingivalis (P. g LPS) is involved not only in periodontal disease but also in the systemic diseases such as psychiatric disorders via neuroinflammation. Here, we investigated the molecular mechanism of KSS and KKT treatment by LPS-induced neuropathy using PC-12 cells. When P. g LPS was administrated during the NGF treatment, the KCC2 expression was decreased in PC-12 cells. P. g LPS treatment also decreased the WNK and phospho SPAK (pSPAK) expression and enhanced GSK-3ß expression that negatively regulates WNK-SPAK signaling. Moreover, when KSS or KKT was administrated before P. g LPS treatment, the decrease of KCC2, WNK and pSPAK was rescued. KSS and KKT treatment also rescued the enhancement of GSK3ß expression by P. g LPS treatment. Furthermore, KSS, KKT and/or oxytocin could rescue behavioral abnormalities caused by P. g LPS treatment by animal experiments. These effects were not shown in the Goreisan treatment, which has been reported to act on the central nervous system. These results indicate that KSS and KKT are candidates for therapeutic agents for neural dysfunction.

Circadian rhythm of PERIOD2::LUCIFERASE expression in the trigeminal ganglion of mice.

Introduction: The trigeminal nerve conveys delicate sensations such as warmth, pain, and tactile pressure in the oral and facial regions, and most trigeminal afferent cell bodies are located in the trigeminal ganglion. Our previous study has shown that sensations in trigeminal nerve innervated areas, specifically in the maxillofacial region, exhibit diurnal variation and that sensitivity changes time-dependently. In this study, we aimed to clarify the rhythm of expression of clock gene in the trigeminal ganglion of mice to elucidate the mechanism of circadian regulation in the same area. Methods: Immunohistochemistry examined the expression of the PER2 protein in the suprachiasmatic nucleus and trigeminal ganglion of wild-type mice. To measure gene expression as bioluminescence, PERIOD2::LUCIFERASE knock-in (PER2::LUC) mice were used. Unilateral trigeminal ganglion and brain sections including the suprachiasmatic nucleus were incubated ex vivo. Bioluminescence levels were then measured using a highly sensitive photodetector. The same experiments were then conducted with Cry1 gene-deficient (Cry1-/- ) or Cry2 gene-deficient (Cry2-/- ) mice. Results: In the trigeminal ganglion, immunohistochemistry localized PER2 protein expression within the neuronal cell body. Mouse trigeminal ganglion ex vivo tissues showed distinct circadian oscillations in PER2::LUC levels in all genotypes, wild-type, Cry1-/- , and Cry2-/- . The period was shorter in the trigeminal ganglion than in the suprachiasmatic nucleus; it was shorter in Cry1-/- and longer in Cry2-/- mice than in the wild-type mice. Conclusion: The expression of Per2 in neurons of the trigeminal ganglion in ex vivo culture and the oscillation in a distinct circadian rhythm suggests that the trigeminal ganglion is responsible for the relay of sensory inputs and temporal gating through autonomous circadian oscillations.