Analgesic Mechanisms of Steroid Ointment against Oral Ulcerative Mucositis in a Rat Model.

Despite the long history of use of steroid ointments for oral mucositis, the analgesic mechanism has not been fully elucidated. In this study, we examined the effects of triamcinolone acetonide (Tmc) on oral ulcerative mucositis-induced pain in conscious rats by our proprietary assay system. Based on evaluations of the physical properties and retention periods in the oral mucosa of human volunteers and rats, we selected TRAFUL® ointment as a long-lasting base. In oral ulcerative mucositis model rats, TRAFUL® with Tmc suppressed cyclooxygenase-dependent inflammatory responses with upregulations of glucocorticoid receptor-induced anti-inflammatory genes and inhibited spontaneous nociceptive behavior. When an ointment with a shorter residual period was used, the effects of Tmc were not elicited or were induced to a lesser extent. Importantly, TRAFUL® with Tmc also improved oral ulcerative mucositis-induced mechanical allodynia, which has been reported to be independent of cyclooxygenase. Ca2+ imaging in dissociated trigeminal ganglion neurons showed that long-term preincubation with Tmc inhibited the hypertonic stimulation-induced Ca2+ response. These results suggest that the representative steroid Tmc suppresses oral ulcerative mucositis-induced pain by general anti-inflammatory actions and inhibits mechanical sensitivity in peripheral nerves. For drug delivery, long-lasting ointments such as TRAFUL® are needed to sufficiently induce the therapeutic effects.

Isoliquiritigenin, an active ingredient of Glycyrrhiza, elicits antinociceptive effects via inhibition of Nav channels.

Glycyrrhiza extract has been used for the treatment of oral and gastric ulcers, but the analgesic mechanism remains unknown. In the present study, we investigated the effects of isoliquiritigenin, an active ingredient of Glycyrrhiza, on Nav channels in vitro and nociceptive behaviors in vivo. In an autopatch-clamp study, isoliquiritigenin inhibited the currents of Nav1.1, Nav1.3, Nav1.6, Nav1.7, and Nav1.8 in a channel expression system. In small- and medium-sized cultured trigeminal ganglion neurons, the compound suppressed Nav currents in many neurons (78%) and Kv currents in all neurons, dose-dependently. In current-clamp mode, isoliquiritigenin blocked action potential generation in many neurons (64%), but it conversely accelerated action potential generation in the remaining neurons. The opposing effects on action potentials were reproduced in a computational simulation of a modified Hodgkin-Huxley-based model, based on the electrophysiological data. In behavioral experiments, local treatment with isoliquiritigenin suppressed nociceptive behaviors in response to oral ulcer development or nociceptive TRP channel agonists in the oral mucosa and hind paw. These results suggest that isoliquiritigenin exerts an analgesic effect predominantly via inhibitory action on Nav channels on sensory nociceptive fibers. This pharmacological mechanism indicates that isoliquiritigenin is useful for pain relief and provides scientific evidence for Glycyrrhiza at the ingredient level.

Real-time evaluation of swallowing in patients with oral cancers by using cine-magnetic resonance imaging based on T2-weighted sequences.

OBJECTIVE: The aim of this study was to evaluate whether a new cine-magnetic resonance imaging (CMRI) technique might be useful for evaluating swallowing function in patients with different types of oral cancers by assessing 12 CMRI-related parameters. STUDY DESIGN: In total, 111 patients with oral cancers were evaluated. We examined whether visualization of fluid flow and determination of flow direction to the trachea or the esophagus were possible with CMRI. We evaluated the correlations between CMRI-related parameters and self-reported dysphagia scores as the status of dysphagia, T classification groups as tumor staging for preoperative patients, alterations in CMRI-related parameters between pre- and postoperative patients, and the degree of invasiveness of oral cancer surgery. RESULTS: We could judge the flow direction to the esophagus on CMRI in all 111 patients. Six CMRI-related parameters showed significant correlations with dysphagia status. Increases in CMRI-related parameters were significantly related to deterioration of swallowing status, as shown by a decrease in self-reported dysphagia scores, advances in the T classification, and degree of invasiveness of oral cancer surgery. CONCLUSIONS: The results of the present study suggest that CMRI can be used to directly visualize swallowing dynamics and objectively evaluate the swallowing complaints of patients with oral cancer.

Advocacy of diagnostic criteria for maxillary incisive canal cysts based on alteration of normal maxillary incisive canals according to aging in Japanese populations.

BACKGROUND: The purpose of the present study was to describe the CT imaging findings of normal incisive canals and incisive canal cysts and propose cut-off values to differentiate between them. METHODS: A total of 220 normal subjects and 40 patients with incisive canal cysts on multi-detector row computed tomography (MDCT) were retrospectively analyzed. The shapes, sizes, anatomic variations, Hounsfield scale values, and so on of maxillary incisive canals and the sizes and Hounsfield scale values of maxillary incisive canal cysts were analyzed. RESULTS: A significant difference in sizes of maxillary incisive canals in normal subjects was found between males and females. The sizes of maxillary incisive canals were significantly wider during aging, but shapes, anatomic variations, and Hounsfield scale values in the maxillary incisive canals were not significantly different with aging. A significant difference in sizes but not Hounsfield scale values was found between normal maxillary incisive canals and maxillary incisive canal cysts. Based on a cut-off of over 6 mm in the width of incisive canals, maxillary incisive canal cysts could not be appropriately diagnosed for subjects over 60 years of age. Over 60 years of age, maxillary incisive canal cysts could be appropriately diagnosed based on a cut-off of over 7.1 mm in width of incisive canals. When maxillary incisive canals of the hourglass types were seen on sagittal sections, significantly more patients had maxillary incisive canal cysts than other types. CONCLUSION: In coincidentally diagnosing asymptomatic incisive canal cysts on imaging, we should apply different cut-offs for the size of the maxillary incisive canal for patients over and under 60 years of age. Specifically, the cut-offs for the long axis of maxillary incisive canal cysts were 7.1 mm for patients over 60 years of age and 6.0 mm for those under 60 years of age. In addition, we should pay attention to wider canals with hourglass shapes as indicative of cystic change of maxillary incisive canals.

Characteristics of diffusion-weighted images and apparent diffusion coefficients of ranulas and other masses in and around the floor of the mouth.

OBJECTIVE: The aim of this study was to evaluate the characteristics of diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) values of ranulas. In addition, to elucidate DWI findings and ADC values of other representative masses in and around the floor of the mouth. STUDY DESIGN: DWI findings and ADC values in 35 patients with ranulas and 33 patients with other masses were retrospectively reviewed with a central focus on cystic masses or lesions that may have cyst-like components in and around the floor of the mouth based on the diagnosis of each respective disease. RESULTS: Ranulas were all well-defined, homogeneous masses with high signal intensity on DWI. The mean ± standard deviation ADC value of the 35 ranulas was 2.59 ± 0.31 × 10-3 mm2/s. There was a significant difference in ADC values between simple and plunging ranulas. On DWI, most other masses were heterogeneous, and most ADC values, except those for thyroglossal duct cysts, hemangiomas, and pleomorphic adenomas, were significantly lower than those for ranulas. CONCLUSIONS: The characteristic DWI and ADC findings of ranulas can be determined accurately, and these data can be significantly useful in the differential diagnosis of many kinds of diseases in and around the oral floor.

Significance and usefulness of imaging characteristics of gubernaculum tracts for the diagnosis of odontogenic tumors or cysts.

We aimed to determine the significance and usefulness of imaging characteristics of gubernaculum tracts (GT) for the diagnosis of odontogenic tumors or cysts. This was a retrospective analysis of relationships between odontogenic or non-odontogenic tumors or cysts and the GT that were visualized using multi-detector computed tomography (MDCT). The relationship between the size of a mass and expansion of the GT in all odontogenic tumors or cysts to which GTs were contiguous on MDCT, was statistically analyzed. Intact or expanded GTs were detected in MDCT images on the top of almost all odontogenic tumors or cysts, but not on non-odontogenic tumors or cysts. Characteristic image findings regarding the relationship between the GT and the odontogenic mass were detected for the respective odontogenic tumors or cysts in which the GTs were contiguous to the mass on MDCT. In ameloblastomas, expansion of the GTs significantly and very strongly correlated with tumor size (r = 0.741, p = 0.0001), but this correlation was very weak in dentigerous cysts (r = 0.167, p = 0.028) and there was no correlation between these parameters in odontogenic keratocysts (r = -0.089, p = 0.557). The imaging characteristics of GTs at the top of masses should be very useful for both the differential diagnosis of the pathological diagnosis of odontogenic masses and for differentiation between odontogenic and non-odontogenic masses.

Functional evaluation of swallowing in patients with tongue cancer before and after surgery using high-speed continuous magnetic resonance imaging based on T2-weighted sequences.

OBJECTIVES: The aim of this study was to determine the usefulness of evaluating the function of swallowing before and after surgery in patients with tongue cancer by using T2-weighted sequences of high-speed continuous magnetic resonance imaging (HSCMRI). STUDY DESIGN: The imaging findings and related parameters on HSCMRI along with those on routine MRI examinations before and after surgery were examined in 19 patients with tongue cancer. In addition, changes in various parameters during 1 year after surgery were evaluated in 10 patients. RESULTS: In most patients examined, the direction of flow to the esophagus could be seen on HSCMRI before and after surgery. Significant correlations were observed among 4 parameters and in the responses to a dysphagia questionnaire. CONCLUSIONS: The results of the present study suggest that the dynamics of swallowing can be directly visualized on HSCMRI by using 4 parameters that permit the evaluation of changes before and after surgery, and this enables objective evaluation of patients' swallowing complaints.