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BackgroundThe fear of pain is closely linked with chronic pain and the resultant impairment of daily life. It has been reported to have a correlation with dental anxiety, making its assessment crucial in dental practice. The present study aimed to develop a Japanese version of the Fear of Pain Questionnaire-III (FPQ-III), an international rating scale, to evaluate psychological characteristics and investigate its association with dental anxiety and gender differences.MethodsAfter forward and backward translation and review, the Japanese version of the FPQ-III was administered to 400 internet monitors, and 100 of them were re-evaluated after a month. Convergent validity was assessed in relation to catastrophic thoughts of dental anxiety and pain, while discriminant validity was evaluated concerning the correlations between anxiety and depression. Confirmatory factor analysis was used to examine the factorial validity of the FPQ-III and a shortened version of the FPQ-9. Item response theory was applied to estimate the discriminative power of each item and draw a test information curve. Structural equation modeling was used to investigate the relationship between pain anxiety and dental anxiety and the gender differences in the model.ResultsData from 400 participants (200 women [50.0%, mean 44.9 ± 14.5 years]) were analyzed. Total scores on the FPQ-III showed good internal validity, intra-examiner reliability, and discriminant validity, indicating convergent validity. Confirmatory factor analysis results supported a three-factor structure, and the FPQ-9 showed a good fit.Discrimination was high, except for two items related to severe pain. Test information curves demonstrated that the FPQ-III and FPQ-9 were more accurate for latent characteristic values between -2 SD and +2 SD. Anxiety about medical pain fully mediated the relationship between fears of minor pain and dental anxiety. No gender differences were observed in this construct, and the factor means for anxiety about severe pain were significantly higher for women than for men.ConclusionThe Japanese versions of the FPQ-III and FPQ-9 demonstrated high reliability and validity for measuring the Fear of Pain in this target population, with high accuracy for a wide range of latent characteristics. The fear of pain was deemed an endogenous factor that was linked to dental anxiety and common to both men and women.

Purpose Stellate ganglion block (SGB) is effective in treating head and neck pain and neuropathic diseases by increasing tissue blood flow through its sympatholytic effect. This study aimed to investigate the relationship between duration of cervical sympathetic nerve block by SGB and its therapeutic efficacy against trigeminal neuropathy after orthognathic surgery. Methods Twenty-eight patients with trigeminal neuropathy were randomly assigned to two groups (mepivacaine and levobupivacaine) according to the drug used for SGB. Increased blood flow, which is a symptom of sympathetic blockade, was recorded for 180 min after SGB. Current perception threshold, warm or cool detection threshold, and tactile detection threshold were measured preoperatively, postoperatively, on day 10 after initiation of SGB, and 3 months postoperatively to compare therapeutic efficacy between the groups. Results The levobupivacaine group had a significantly longer duration of increased blood flow compared with the mepivacaine group. Values of current perception threshold, warm and cool detection threshold, and tactile detection threshold significantly improved in the levobupivacaine group on day 10 after initiation of SGB and 3 months postoperatively. Conclusion A prolonged increase in blood flow due to long-term sympatholytic effects accelerates the therapeutic efficacy of SGB in trigeminal neuropathy.

Objectives The shapes of gubernaculum tracts (GTs) in molars as accessional teeth remain unidentified. To elucidate imaging peculiarities of GTs in molars with aging on multidetector‐row computed tomography (MDCT). Material and methods This retrospective study was conducted using CT images, including maxillary and mandibular molars, with no abnormal findings from 239 patients. Shapes of alveolar bone, GTs, and dental sacs of the maxillary and mandibular molars were analyzed multi‐sectionally. Correlations between 2‐ and 3‐dimensional imaging figures of GTs in molars and chronological age or stage of molar formation were analyzed. Results Some forms of GTs in maxillary and mandibular third molars were observed. In the early stage, GTs were visualized as bone defect lines on the dentition and grooves on the mesial alveolar crest continuous with the dental sac to mesial tooth bud. GTs of the third molar formed a J‐shape in maxillary teeth and Y‐shape in mandibular teeth in the middle stage, as alveolar bone around the GT developed. In the mature stage, the course of the GT changed to straight and perpendicular. Some GT forms were also identified in first and second molars. Significant correlations were found between GT alterations and chronological age or stage of molar formation. Moreover, tracts continuing from the distal side of mandibular third molars were detected. Conclusions This paper describes the peculiarities and process of progression for GTs in molars, and the existence of tracts continuing from the distal side of mandibular third molars, unlikely dentition with deciduous predecessors. These preliminary data should prove beneficial for studies focusing on GTs in molars.

Upper airway obstruction (UAO) and oxygen desaturation are risk factors for major complications of intravenous sedation (IVS) in pediatric dental patients. This study aimed to investigate the use of a nasal high-flow (NHF) system for the prevention of UAO and oxygen desaturation in pediatric dental patients under IVS.The authors implemented a prospective randomized design. Thirty pediatric patients (aged 3 to 12), scheduled for dental treatment under IVS, were enrolled in this study. The subjects were randomly assigned to 1 of 2 groups: patients who received oxygen at 5 L/minute through a nasal cannula (NC group) and patients who received oxygen at 2 kg/L/minute, up to a maximum of 30 L/minute, through the NHF system (NHF group). The predictor variable was flow rate. The primary outcome variable was the need for intervention during treatment, and the secondary outcome variable was the lowest peripheral capillary oxygen saturation values during the procedure. Additional study variables measured included patient age, gender, weight, height, and surgical duration. The Mann-Whitney U test and Fisher exact test were used for statistical analysis, with P .05 considered as significant.Both the NC (n = 15; mean age, 6.2 ± 2.3) and NHF (n = 15; mean age, 5.9 ± 2.5) groups had a male:female ratio of 2:1. The use of the NHF system significantly improved the lowest peripheral capillary oxygen saturation values during treatment (P .05). Jaw lifting, to relieve UAO and facilitate spontaneous breathing, was required in both the NC (n = 10) and NHF (n = 3) groups (P .05). The need for interventions during treatment was significantly lower in the NHF group (P .05).The results of this study suggest that the use of the NHF system can prevent UAO and improve the respiratory condition of pediatric dental patients under IVS.

Background: Assessment of dental anxiety using a validated questionnaire is important for its management and survey. Objective: The aim of this cross-sectional online survey was to evaluate the psychometric properties of the Japanese version of the Single Dental Anxiety Question (SDAQ). Methods: The single question was translated into Japanese following the forward-backward method. Four hundred Japanese internet monitors (age 20–79 years) were included in the study. Sensitivity–specificity analysis and the Kappa coefficient were calculated against the Modified Dental Anxiety Scale (MDAS) using the 19 cutoff score for high dental anxiety. Criterion validity was evaluated using age, gender, dental attendance pattern, negative dental experiences, and subjective oral health. Results: Among these subjects, 11% were found to have high dental anxiety on the MDAS score and 9% rated themselves as very afraid of SDAQ. The Kappa coefficient between the MDAS cutoff score and the SDAQ classification was 0.58, the sensitivity was 0.56, and the specificity was 0.97. The SDAQ was associated with gender (P = 0.018), dental attendance pattern (P = 0.020), negative dental experiences (P < 0.001), and subjective oral health (P < 0.001). Conclusion: The Japanese version of the SDAQ has good criterion and construct validity but lower sensitivity than the original version. It can be used to assess dental anxiety in large dental surveys or clinical settings where a multi-item questionnaire is not feasible.

The objective was to introduce a new technique for visualizing the three-dimensional (3D) movements of velopharyngeal-related muscles using high-speed cine-magnetic resonance imaging (MRI) based on T2-weighted sequences. The evaluation of phonation- and water swallowing-related events was performed in 11 healthy subjects. Specifically, whether cine-MRI could precisely visualize normal velopharyngeal function during these two events was examined. The 3D movements of the soft palate, superior pharyngeal constrictor muscles, and levator veli palatini muscles were visualized in all 11 subjects. A noteworthy finding was that the magnetic resonance signals of the superior constrictor pharyngeal muscles and the levator veli palatini muscles were significantly higher during phonation and during water swallowing than at rest. This initial study suggests that the 3D movements of velopharyngeal-related muscles can be successfully and precisely visualized without side effects. The magnetic resonance signal changes seen in the superior pharyngeal constrictor and levator veli palatini muscles using the technique described here should be useful to develop better methods of evaluation of velopharyngeal function.

Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) is a rare form of primary headache, classified as trigeminal autonomic cephalalgia. Since the underlying mechanism of the pathogenesis has not yet been determined, a standardized therapeutic strategy for SUNCT is unavailable. We present a case of SUNCT syndrome with successful pain relief by intravenous administration of ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist.A 56-year-old male patient reported severe throbbing and shooting pain in forehead, temporal and periorbital region. We confirmed conjunctival injection, lacrimation, blepharoptosis, and miosis as symptoms related to autonomic activity, and made a diagnosis of SUNCT based on ICHD-3 beta. Numerous treatments were attempted, including pregabalin, gabapentine, nonsteroidal antiinflammatory drugs, acetaminophen, steroids, antidepressants, triptans, nerve blocks, and intravenous lidocaine with unsatisfactory results. Intravenous administration of ketamine (0.4 mg/kg) for one hour, was found to relieve the severe pain.Intravenous ketamine can effectively treat SUNCT syndrome. This case demonstrated that involvement of NMDAR could be one of the mechanisms of SUNCT syndrome pathogenesis and establish a therapeutic strategy for this pain syndrome.

This study was done to determine whether the sublingual gland ducts could be visualized and/or their function assessed by MR sialography and dynamic MR sialography and to elucidate the clinical significance of the visualization and/or evaluation of the function of sublingual gland ducts by clinical application of these techniques. In 20 adult volunteers, 19 elderly volunteers, and 7 patients with sublingual gland disease, morphological and functional evaluations were done by MR sialography and dynamic MR sialography. Next, four parameters, including the time-dependent changes (change ratio) in the maximum area of the detectable sublingual gland ducts in dynamic MR sialographic images and data were analyzed. Sublingual gland ducts could be accurately visualized in 16 adult volunteers, 12 elderly volunteers, and 5 patients. No significant differences in the four parameters in detectable duct areas of sublingual glands were found among the three groups. In one patient with a ranula, the lesion could be correctly diagnosed as a ranula by MR sialography because the mass was clearly derived from sublingual gland ducts. This is the first report of successful visualization of sublingual gland ducts. In addition, the present study suggests that MR sialography can be more useful in the diagnosis of patients with lesions of sublingual gland ducts.

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.

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.

Introduction. A careful assessment of dental anxiety is necessary for its management. The Modified Dental Anxiety Scale (MDAS) is one of the most commonly used questionnaires to measure dental anxiety in the world. The reliability and validity of the Japanese version of MDAS have been demonstrated using undergraduates and a few patients with dental anxiety. The aim of the present study was to examine the reliability and validity of the Japanese version of the MDAS using a wide range of age samples in dental clinics. Methods. A total of 275 outpatients (145 men and 130 women; 21–87 years) from two dental clinics participated in the present study. Dental anxiety was assessed using the Japanese version of the MDAS and the Dental Fear Survey (DFS). The psychometric evaluation included exploratory factor analysis, and Cronbach’s α was used to evaluate for internal consistency. Criterion validity was assessed by correlating the MDAS and DFS scores using Spearman’s correlation coefficient. validity was evaluated by examining related factors’ differences in the MDAS score (e.g., sex and negative dental experiences). Results. Six patients (2.2%) reported high levels of dental anxiety (MDAS score ≥ 19). The internal consistency of the MDAS score was high (Cronbach’s α = 0.88). Dental anxiety was significantly higher among women (P=0.007), in patients with previous negative dental experiences (P<0.001), and among those with lower frequencies of dental visits (P<0.001). The MDAS score was significant and related to age (r = 0.48) and the DFS score (r = 0.87). Factor analysis revealed all items measured only one construct. Conclusions. The Japanese version of the MDAS score was found to be a reliable and valid measure of dental anxiety among dental outpatients. It could be useful for the Japanese dental practitioner to measure dental anxiety in a clinical setting.

Intravenous sedation (IVS) is commonly used to complete dental treatment for uncooperative pediatric patients. Propofol (PRO) is widely used for IVS because of its short context sensitive half-time and amnestic effect. However, administering PRO to patients who have a history of egg anaphylaxis is still somewhat controversial. The evidence that supports the potential risks for allergic reactions following PRO use in patients with egg allergies is limited with some anesthesiologists recommending against its use in these patients. Alternative drug regimens for procedural sedation in this population are therefore desirable. Dexmedetomidine (DEX), a selective α-2 agonist, has antianxiety and sedative properties and has been widely used not only for procedural sedation with mild inhibitory effects on respiration but also during minor surgeries for its analgesic effect. In this paper, we describe the successful administration of a combination of DEX and low-dose midazolam (MDZ) for sedation in an uncooperative pediatric patient. Both DEX and MDZ have been reported as safe and useful sedatives for dental treatment, and their combination may provide a helpful option for IVS of pediatric patients for whom PRO is not preferred.

The aim of this study was to determine whether the evaluation of neurovascular compression (NVC) using new criteria on magnetic resonance (MR) cisternography improves the prediction of the curative effects of carbamazepine (CBZ) in trigeminal neuralgia (TN). In this study, a new analysis of NVC using MR cisternography was performed retrospectively for 280 patients with clinical signs and symptoms suggesting TN. The new analysis examined whether the site of the NVC was less than 3mm from the edge of the exit point and within the first third of the root entry zone on MR cisternography. Prediction of the curative effects of CBZ using the new evaluation of distance to the NVC improved on the predictive ability of the previous method of calculating the NVC volume (Mantel-Haenszel coefficient, P 5mm3. The evaluation of NVC on MR cisternography using this new approach appears to be more useful than the previous method for predicting the initial treatment response in patients with TN.

Purpose Hypoxia is a major complication in dental patients under intravenous sedation (IVS). A nasal high-flow (NHF) system has been reported to achieve effective oxygenation in patients with sleep apnea syndrome. This study investigated the ability of the NHF system to prevent hypoxia in dental patients under IVS. Materials and Methods Thirty patients scheduled for dental treatment under IVS were enrolled. Patients were randomly divided into 3 groups: patients spontaneously breathing oxygen at 5 L/minute through a nasal cannula (NC5 group), patients administered oxygen at 30 L/minute through the NHF system, and patients administered oxygen at 50 L/minute through the NHF system. Hypnosis was induced by bolus administration of midazolam (0.05 mg/kg) followed by continuous administration of propofol (target blood concentration, 1.2 to 2 μg/mL). Noninvasive blood pressure, peripheral capillary oxygen saturation (SpO2), heart rate, and bispectral index values were recorded every 2.5 minutes before the induction of anesthesia. Interventions, such as jaw lifting, were recorded during IVS and arterial blood gas analysis was performed at the end of sedation. Patient and surgeon satisfaction with IVS was evaluated by interview. Results Minimum SpO2 was lowest in and surgeons were least satisfied with the NC5 group. In addition, interventions were required most frequently in the NC5 group (P < .05). Compared with the NC5 group, use of the NHF system improved partial pressures of oxygen and carbon dioxide in dental patients under IVS (P < .05). Conclusions These results suggest that use of the NHF system can prevent hypoxia in dental patients under IVS. Further studies are necessary to determine the appropriate flow rate and indications for NHF in obese patients.

Recent evidence implicates endothelin in nociception, but it is unclear how endothelin activates trigeminal ganglion (TRG) neurons. In the present study, we investigated the expression of the endothelin receptors ETA and ETB and endothelin-induced responses in rat TRG neurons. Double-immunofluorescence studies demonstrated that ETA and ETB were expressed in TRG neurons and that 26% of ETA- or ETB-expressing neurons expressed both receptors. During whole-cell patch-clamp recording, endothelin-1 enhanced an induced current in response to capsaicin, a TRPV1 agonist, in approximately 20% of dissociated neurons. The enhancement was blocked by the PKC inhibitor chelerythrine and by the ETA antagonist BQ-123, but not by the ETB antagonist BQ-788. Ca2+-imaging showed that endothelin-1 increased the intracellular Ca2+ concentration in more than 20% of the dissociated neurons. Importantly, unlike the effect of endothelin-1 on capsaicin-induced current, the Ca2+ response was largely suppressed by BQ-788 but not by BQ-123. These results suggest that ETA-mediated TRPV1 hyperactivation via PKC activation and ETB-mediated Ca2+ mobilization occurs in different subsets of TRG neurons. These endothelin-induced responses may contribute to the induction of orofacial pain. The ETB-mediated function in TRG neurons is a special feature in the trigeminal system because of no ETB expression in dorsal root ganglion neurons.

Purpose We examined the effects of sweet taste stimulation on pain tolerance threshold (PTT) of oral mucosa in children. Subjects and methods Subjects comprised 10 children (mean age, 7.3±1.2 years) for whom PTT of oral mucosa was measured 2min after oral administrations of sucrose or xylitol and water. Sine wave current stimulation (2kHz, 250Hz and 5Hz, SWCS) which can stimulate sensory nerve fiber selectively (A β , A δ and C) was used to measure PTT. Results Sweet taste stimulation with sucrose or xylitol increased oral mucosa PTT in children, but not in adults. No difference in the increased PTT was seen between sucrose and xylitol. Conclusions Oral administration of sucrose and xylitol may potentially relieve pain associated with local anesthetic injections in children.

Takayasu arteritis is a rare chronic progressive panendarteritis involving the aorta and its main branches. Anesthesia in patients with this disease can be complicated by severe uncontrolled hypertension, end-organ dysfunction, and stenosis of major blood vessels. In this case, general anesthesia was induced with sevoflurane and remifentanil without complications. To prevent intraoperative complications, we conducted intubation with a rigid video laryngoscope with careful consideration of the concentrations of analgesics and sedatives used. This case demonstrates the importance of anesthetic techniques for maintaining adequate tissue perfusion without hemodynamic changes in the anesthetic management of patients with Takayasu arteritis.

Venipuncture is often accompanied by pain, which can compromise dental care and foment distrust toward dental care providers. The aim of the present study was to identify sites on the forearm and hand that have the greatest pain tolerance threshold (PTT) during venipuncture.The PTT was estimated in 20 healthy volunteers using a noninvasive nerve conduction threshold device. The subjects self-stimulated 5 sites (median cubital vein, cephalic vein at the cubitus, basilic vein, cephalic vein at the carpus, and superficial dorsal vein) at 2 kHz, 250 Hz, and 5 Hz. We measured the stimulation intensity before the subject deactivated the device. Differences in the average PTT values at each site were compared using the Kruskal-Wallis and Scheffé tests. P.05 was considered to indicate statistical significance.The PTT was significantly greater at the superficial dorsal vein than at the basilic vein for all 3 noninvasive nerve conduction threshold frequencies (P.05). The estimated PTT was significantly greater at the superficial dorsal vein than at the median cubital vein and cephalic vein at the carpus in response to 250-Hz stimulation (P.05).The greater PTT of the superficial dorsal vein suggests that venipuncture at this site should result in the lowest pain intensity among all upper limb sites.

During dental treatments, intraoral appliances frequently induce traumatic ulcers in the oral mucosa. Such mucosal injury-induced mucositis leads to severe pain, resulting in poor quality of life and decreased cooperation in the therapy. To elucidate mucosal pain mechanisms, we developed a new rat model of intraoral wire-induced mucositis and investigated pain mechanisms using our proprietary assay system for conscious rats. A thick metal wire was installed in the rats between the inferior incisors for one day. In the mucosa of the mandibular labial fornix region, which was touched with a free end of the wire, traumatic ulcer and submucosal abscess were induced on day 1. The ulcer was quickly cured until next day and abscess formation was gradually disappeared until five days. Spontaneous nociceptive behavior was induced on day 1 only, and mechanical allodynia persisted over day 3. Antibiotic pretreatment did not affect pain induction. Spontaneous nociceptive behavior was sensitive to indomethacin (cyclooxygenase inhibitor), ONO-8711 (prostanoid receptor EP1 antagonist), SB-366791, and HC-030031 (TRPV1 and TRPA1 antagonists, respectively). Prostaglandin E2 and 15-deoxyΔ12,14-prostaglandin J2 were upregulated only on day 1. In contrast, mechanical allodynia was sensitive to FSLLRY-NH2 (protease-activated receptor PAR2 antagonist) and RN-1734 (TRPV4 antagonist). Neutrophil elastase, which is known as a biased agonist for PAR2, was upregulated on days 1 to 2. These results suggest that prostanoids and PAR2 activation elicit TRPV1- and TRPA1-mediated spontaneous pain and TRPV4-mediated mechanical allodynia, respectively, independently of bacterial infection, following oral mucosal trauma. The pathophysiological pain mechanism suggests effective analgesic approaches for dental patients suffering from mucosal trauma-induced pain.

Although recent evidence suggests that central glial hyperactivation is involved in cancer-induced persistent pain, the time course of this hyperactivation and the glial contribution to pain hypersensitivity remain unclear. The present study investigated the time-dependent spatial changes of microglial and astrocytic hyperactivation in the trigeminocervical complex, which consists of the medullary (MDH) and upper cervical (UCDH) dorsal horns, and pain-related behaviors in a rat facial cancer model in which Walker 256B-cells are inoculated into the vibrissal pad. In this model, the tumors grew within the vibrissal pad, from which sensory nerve fibers project into the MDH, but did not expand into the infraorbital region, from which fibers project into the UCDH. Nevertheless, mechanical allodynia and thermal hyperalgesia were observed not only in the vibrissal pad but also in the infraorbital region. Western blotting and immunofluorescence studies indicated that microglia were widely activated in the trigeminocervical complex on day 4 and gradually inactivated by day 11. In contrast, astrocytes were only activated in the MDH on day 4; the hyperactivation later expanded into the UCDH. Daily administration of the glial hyperactivation inhibitor propentofylline beginning on day 4 suppressed the glial hyperactivation on later days. Propentofylline treatment largely prevented allodynia/hyperalgesia in the infraorbital region beginning on day 5, although established allodynia/hyperalgesia in the vibrissal pad was less sensitive to the treatment. These results suggest that central glial hyperactivation, transient microglial hyperactivation and persistent astrocytic hyperactivation, contributes to the development of pain hypersensitivity but not to the maintenance of pain in this model.

Peripheral and central glial activation plays an important role in development of pain hypersensitivity induced by inflammation and nerve injury. However, the involvement of glial cells in cancer pain is not well understood. The present study evaluated the peripheral and central glial activation and the effect of an inhibitor of glial activation, propentofylline, on pain-related behaviors in a rat facial cancer model of the growth of Walker 256B cells in the unilateral vibrissal pad until days 3-4 post-inoculation. As compared with sham animals, the facial grooming period was prolonged, the withdrawal latency to radiant heat stimulation was shortened, and the withdrawal threshold by von Frey hair stimulation was decreased at the inoculated region, indicating the development of spontaneous pain, thermal hyperalgesia and mechanical allodynia. In immunostainings for Iba1 and glial fibrillary acidic protein (GFAP), although there were no morphological changes of GFAP-immunopositive satellite glial cells in the trigeminal ganglion, Iba1-immunopositive microglia and GFAP-immunopositive astrocytes in the medullary dorsal horn showed large somata with cell proliferation. After the daily i.p. administration of propentofylline beginning pre-inoculation, the central glial activation was attenuated, the prolonged facial grooming was partially suppressed, and the induced allodynia and hyperalgesia from day 2 were prevented, without a change in tumor size. These results suggest that glial activation in the CNS, but not in the peripheral nervous system, mediates the enhancement of spontaneous pain and the development of allodynia and hyperalgesia at an early stage in the facial cancer model.