Background: In alveolar bone graft surgery, local administration of ropivacaine at the iliac bone donor site is expected to have an analgesic effect. However, its effects on autonomic nervous system activity and circulatory dynamics are unknown. Aims: This study aimed to assess the effects of local ropivacaine administration to the iliac region under general anesthesia by analyzing changes in autonomic nervous system activity and circulatory dynamics. Methods: We retrospectively reviewed medical records of patients who underwent iliac bone grafting under general anesthesia between May 2021 and December 2022. At the end of surgery, ropivacaine was administered locally in the iliac region. Heart rate variability (HRV), heart rate (HR), and systolic blood pressure (SBP) were analyzed 5 min prior to (baseline) and 5 min following (postadministration) ropivacaine administration. Results: Seventeen patients were included in the analysis. The low/high frequency ratio was significantly elevated after ropivacaine administration compared with baseline (p < 0.05). No significant changes were observed in high frequency, HR, or SBP (p < 0.05). Conclusion: Local administration of ropivacaine in the iliac region under general anesthesia resulted in detectable neurological changes, as evidenced by HRV analysis, though conventional circulatory parameters remained unchanged. HRV may provide sensitive detection of perioperative stress beyond what is captured by hemodynamic measures alone.

The trigeminocardiac reflex (TCR) is clinically defined as the sudden onset of increased parasympathetic activity resulting from stimulation of the trigeminal nerve. This reflex increases parasympathetic tone and can lead to significant bradycardia and hypotension. We report the case of severe bradycardia and hypotension that occurred under general anesthesia during insertion of a cotton swab into the nasal cavity. A 57-year-old woman was scheduled for nasotracheal intubation for oral surgery, and following loss of consciousness, intubation was initiated using cotton swabs soaked in a solution of 2% lidocaine and 1:100,000 epinephrine that were inserted through the left nostril. The patient immediately developed severe bradycardia and hypotension which were managed with intravenous ephedrine after removing the cotton swabs rather than atropine due to concerns related to closed-angle glaucoma. The patient responded promptly to the ephedrine bolus, and no further complications occurred. It was assumed that the ophthalmic (V1) and maxillary (V2) branches of the trigeminal nerve were stimulated by the cotton swabs being inserted into the nasal cavity, triggering the TCR. Anesthesiologists need to be aware of the risks associated with administering mydriatic drugs such as ephedrine and epinephrine, which are relatively contraindicated, as well as atropine to patients with closed-angle glaucoma.

Dentists must provide basic life support (BLS) until the arrival of emergency services. Improving educational quality and expanding training opportunities in dental schools can enhance patient survival rates. Traditionally, primary life support training for dental students was conducted in person; however, in-person practice has become challenging during the recent coronavirus disease (COVID-19) pandemic caused by the novel coronavirus. Our objective was to examine how monitor feedback from a cardiopulmonary resuscitation (CPR) simulator and monitoring equipment, versus instructor feedback, affects the quality of BLS training for dental students, and to evaluate effective self-study methods during the pandemic. All participants (n = 40) underwent a pretraining test to assess their baseline technical skills in providing CPR. The students were then randomly divided into the following two groups: monitor feedback and instructor feedback. After the training, a post-test was administered using the same method as that used for the pretest. We statistically analyzed changes in chest compression (CC) depth, CC rate, CC fraction, and tidal volume before and after training in the two groups. The analysis included 34 participants (17 per group) after excluding those lost to attrition. In the monitor feedback group, compared with the pretest, the post-test revealed a significantly improved CC depth. Meanwhile, the CC rate improved significantly in the instructor feedback group. Regarding CC depth, monitor feedback led to improved compression depth compared to instructor feedback. Conversely, instructor feedback on the CC rate led to superior results compared to monitor feedback. Training programs should provide monitor feedback for CC depth and instructor feedback on the CC rate to establish more effective self-study training methods. Different feedback types influence specific aspects of CPR and that further validation is required.

TRIAL REGISTRATION:UMIN Clinical Trials Registry, UMIN 000054970.

IntroductionThe vasovagal reflex is the most frequent emergency that occurs during dental procedures, but its underlying mechanism is not understood. In this study, we conducted autonomic monitoring of patients with a history of vasovagal reflexes.Case descriptionWe focused on the high-frequency component, an indicator of parasympathetic activity, and interrupted the treatment when the high-frequency component increased. Treatment was then resumed after confirming that there was no mood disturbance and no increase in the high-frequency component. In another patient with a history of dental treatment-induced vasovagal reflex, autonomic activity during treatment was measured under atropine sulfate hydrate administration.DiscussionAnalysis of heart rate variability during the vasovagal reflex showed that parasympathetic hyperactivity was followed by sympathetic hyperactivity, indicating real-time changes in autonomic nervous system activity. In addition, the high-frequency component, which decreased after atropine sulfate hydrate administration, did not increase during treatment, along with the low-frequency to high-frequency ratio, a measure of sympathetic nervous system activity, and the vasovagal reflex did not occur. We believe that the visualization of a patient’s autonomic nervous system activity during dental treatment will improve the quality of systemic management and lead to the realization of a safe and comfortable treatment environment.

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. The present study clarified the rat trigeminal ganglion cells' three-dimensional localization. Fast blue was injected into 12 sites of the orofacial regions, and ganglion cell bodies innervating these regions were labeled. The labeled trigeminal ganglia were cleared by modified 3DISCO, imaged with confocal laser-scanning microscopy, and reconstructed. dagger image

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.

OBJECTIVE:Imbalanced autonomic nervous system (ANS) activity raises concerns about the development of systemic complications during dental treatment. The purpose of this study was to determine whether a psychological test (Toho Medical Index (TMI)) prior to the impacted mandibular third molar extraction can identify patients with potentially imbalanced autonomic function. MATERIALS AND METHODS:In this prospective study, 34 healthy adult patients with no history of systemic disease were assigned to either the autonomic imbalance group (type II, III, IV) or the control group (type I) based on the results of the TMI. We evaluated sympathetic nervous system activity (low/high frequency (LF/HF)), parasympathetic nervous activity, heart rate (HR), and systolic blood pressure (SBP) values before extraction of the impacted mandibular third molar. RESULTS:LF/HF and SBP in the autonomic imbalance group were significantly higher preoperatively than those in the control group. In addition, preoperative HF values were significantly lower in the autonomic imbalance group compared to those in controls (Mann-Whitney U test, p < 0.05); no significant group differences in HR were found (Mann-Whitney U test, p < 0.05). CONCLUSION:ANS activity before extraction of the impacted mandibular third molar was assessed subjectively using the TMI and objectively using HR variability analysis. Our findings suggest that some patients do not have symptoms specific to dysautonomia but have an imbalance of autonomic function before extraction of the impacted mandibular third molar, and TMI can identify such patients.

Aim: The effect of listening to music before tooth extraction on the autonomic nervous system and psychological state remains unclear. This prospective study explored the hypothesis that playing music before the extraction of an impacted mandibular third molar would stabilize patients' autonomic nervous system activity and circulatory dynamics. Methods: Thirty-six patients were randomized into two groups: control and music. Patients in the music group listened to music before tooth extraction. Heart rate variability and circulatory dynamics were recorded during the procedure. The Modified Dental Anxiety Scale and State Trait Anxiety Inventory scale scores were recorded before the procedure, and the latter was used to assess postoperative anxiety scores. Results: Sympathetic nervous activity significantly increased in the control group during the administration of local anesthesia, bone removal, and extraction (p < 0.01), although this increase was lower in the music group during the administration of local anesthesia and extraction (p < 0.05). In the music group, the postoperative anxiety score was significantly lower than the preoperative score (p < 0.05). Conclusion: Playing music preoperatively may help reduce sympathetic nerve activity during the administration of local anesthesia and tooth extraction.

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.

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-3β 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 GSK3β 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.

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.

IntroductionThe 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. MethodsImmunohistochemistry 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. ResultsIn 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. ConclusionThe 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.

The circadian rhythms of physiology and behavior are based on molecular systems at the cellular level, which are regulated by clock genes, including cryptochrome genes, Cry1 and Cry2. In mammals, the circadian pacemaker in the suprachiasmatic nucleus (SCN) of the hypothalamus maintains the circadian rhythms throughout the body. Cry1 and Cry2 play distinct roles in regulating the circadian rhythm. However, the different effects of manipulating clock genes in heterozygous and homozygous alleles, Cry1 and Cry2, remain unclear. Therefore, this study aimed to understand the haplosufficiency of cryptochrome genes in regulating the circadian system. We examined wheel-running activity rhythms and PER2::LUC expression rhythms in SCN slices and pituitary explants in mice. Compared with wild-type mice, Cry1(-/-) or Cry2(-/-) mice had shortened or lengthened periods in free-running behavioral rhythms and PER2::LUC expression in the SCN and pituitary gland. Cry1(+/-) mice had similar circadian rhythms as wild-type mice, although Cry2(+/-) mice had lengthened periods. The amplitude of PER2::LUC expression exhibited faster damping in Cry1(-/-) mice. Therefore, Cry1 deficiency affects the circadian period length and stability of the circadian system. A single allele of Cry2 deficiency affects the circadian rhythm, whereas that of Cry1 deficit is compensated.

Recent evidence has suggested that pituitary adenylate cyclase-activating polypeptide (PACAP) has critical roles in central and peripheral pathways, such as spino-parabrachio-amygdaloid and hypothalamic-pituitary-adrenal pathways, mediating stress-related negative emotional behaviors. Although it is well established that there is a great degree of comorbidity of chronic pain and negative emotional behaviors, the cellular mechanism underlying chronic pain and anxiety/depression interaction still remains to be elucidated. Here, we evaluated possible involvement of PACAP signaling in the development of anxiety- and depression-like behaviors after peripheral nerve injury in mice. We observed that spinal nerve ligation (SNL) induced anxiety- and depression-like behaviors lasting for at least 3 weeks in wild-type (PACAP +/+) mice. However, the development of SNL-induced anxiety- and depression-like behaviors was almost completely abrogated in PACAP -/- mice. Furthermore, we found that selective overexpression of PACAP by the infection of adeno-associated virus in the hypothalamic paraventricular nucleus (PVN), but not neighboring ventromedial hypothalamus, region resulted in the induction of anxiety-like behavior. In contrast, siRNA-mediated knockdown of PVN PACAP attenuated the development of SNL-induced anxiety- but not depressive-like behavior. Our data support that PVN PACAP signaling is involved in an important mechanism underlying the anxiety-like behaviors in peripheral neuropathic pain condition.

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.

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.

Linalool odor exposure induces an analgesic effect in mice. This effect disappeared in the anosmic model mice, indicating that olfactory input evoked by linalool odor triggered this effect. Furthermore, hypothalamic orexinergic neurons play a pivotal role in this effect. However, the neuronal circuit mechanisms underlying this effect have not been fully addressed. In this study, we focused on the descending orexinergic projection to the spinal cord and examined whether this pathway contributes to the effect. We assessed the effect of intrathecal administration of orexin receptor antagonists on linalool odor-induced analgesia in the tail capsaicin test. We found that the selective orexin type 1 receptor antagonist, but not the selective orexin type 2 receptor antagonist, prevented the odor-induced analgesic effect. Furthermore, immunohistochemical analyses of c-Fos expression induced by the capsaicin test revealed that neuronal activity of spinal cord neurons was suppressed by linalool odor exposure, which was prevented by intrathecal administration of the orexin 1 receptor antagonist. These results indicate that linalool odor exposure drives the orexinergic descending pathway and suppresses nociceptive information flow at the spinal level.

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.

Management of time and circadian disruption is an extremely important factor in basic research on pain and analgesia. Although pain is known to vary throughout the day, the mechanism underlying this circadian variation remains largely unknown. In this study, we hypothesized that the process of pain transmission to the central nervous system (after receiving nociceptive stimuli from outside the body) would show day-night differences. Ten-week-old male mice were kept under a strict 12/12-h light/dark cycle for at least 10 days. Formalin was then injected into the second branch region of the trigeminal nerve and the duration of pain-related behaviors (PRBs) was assessed. Immunohistochemical staining was then performed, and the c-Fos-immunopositive cells in the trigeminal spinal tract subnucleus caudalis (Sp5C) were counted. The results showed that the duration of PRBs was longer and the number of c-Fos immunopositive cells in the Sp5C was higher at nighttime than during the day. In addition, the trigeminal ganglia (TG) were extracted from the mice and examined by quantitative real-time PCR to evaluate the daytime and nighttime expression of nociceptive receptors. The results showed that the mRNA expression of transient receptor potential ankyrin 1 in the TG was significantly higher at night than during the day. These results suggest that pain in the trigeminal nerve region is more intense at nighttime, when rodents are active, than during the daytime, partly due to differences in nociceptor expression.