Psychometric evaluation of the Japanese version of the fear of pain questionnaire-III and its association with dental anxiety: a cross-sectional study.

BACKGROUND: Fear of pain is a significant concern related to chronic pain and its impact on daily functioning. It is also associated with dental anxiety, highlighting its relevance in dental practice. This study aimed to validate the Japanese version of the Fear of Pain Questionnaire-III (FPQ-III) and explore its relationship with dental anxiety. METHODS: 400 participants completed the Japanese version of the FPQ-III, with 100 participants re-evaluated after one month. Convergent validity was tested against dental anxiety and pain catastrophizing, while discriminant validity was assessed by examining general anxiety and depression correlations. Confirmatory factor analysis was used to examine the factorial validity of the FPQ-III and a shortened version of the FPQ-III (FPQ-9). Item response theory was applied for each subscale to estimate the discriminative power of each item and draw a test information curve. Structural equation modeling (SEM) was used to investigate the relationship between fear of pain and dental anxiety. RESULTS: Data from 400 participants (200 women, 44.9 ± 14.5 years) were analyzed. The FPQ-III showed good internal validity, intra-examiner reliability, discriminant validity, and convergent validity. Confirmatory factor analysis results supported a three-factor structure, and the FPQ-9 showed a good fit. Test information curves demonstrated that the FPQ-9 maintained high accuracy over a similarly wide range as the FPQ-III. SEM revealed that fear of minor pain was associated with dental anxiety via fear of medical pain even in individuals without painful medical or dental experiences (indirect effect 0.48 [95% CI: 0.32-0.81]). Fear of severe pain tended to be higher in individuals with chronic pain compared to those without (latent mean values 0 vs. 0.27, p = 0.002) and was also associated with dental anxiety via fear of medical pain in women (indirect effect 0.15 [95% CI: 0.01-0.34]). CONCLUSION: The Japanese version of the FPQ-9 demonstrated high reliability and validity, making it a valuable tool in dental clinical and research settings. It provides insights into the fear of pain among individuals with chronic pain and dental anxiety, informing potential intervention strategies.

Referred sensations in the orofacial region are associated with a decreased descending pain inhibition and modulated by remote noxious stimuli and local anesthesia.

ABSTRACT: Referred sensation (RS) as a specific clinical phenomenon has been known for a long time, although the underlying mechanisms remain unclear. The aims of this study were to assess if (1) healthy individuals who experienced RS had a less active endogenous pain system when compared with those who did not; (2) activation of descending pain inhibition mechanisms can modulate RS parameters; and finally, (3) a transient decrease in peripheral afferent input because of a local anesthetic (LA) block in the masseter muscle can modulate RS parameters. To assess these, 50 healthy participants were assessed in 3 different sessions. In the first session, conditioned pain modulation (CPM) as well as mechanical sensitivity and RS at the masseter muscle were assessed. In the same session, participants who experienced RS had their mechanical sensitivity and RS assessed again while undergoing a CPM protocol. In the second and third sessions, participants had their mechanical sensitivity and RS assessed before and after receiving an injection of 2 mL of LA and isotonic saline into the masseter muscle. The main findings of this study were (1) participants who experienced RS during standardized palpation exhibited increased mechanical sensitivity ( P < 0.05, Tukey post hoc test) and decreased CPM ( P < 0.05, Tukey post hoc test) when compared with those who did not; RS incidence ( P < 0.05, Cochran Q test), frequency ( P < 0.05; Friedman test), intensity ( P < 0.05, Tukey post hoc test), and area ( P < 0.05, Tukey post hoc test) were all significantly reduced when assessed (2) during a painful conditioning stimulus and (3) after LA block. These novel findings highlight that RS in the orofacial region are strongly modified by both peripheral and central nervous system factors.

Prolonged blockade of the cervical sympathetic nerve by stellate ganglion block accelerates therapeutic efficacy in trigeminal neuropathy.

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.

Pain Relief in Short-Lasting Unilateral Neuralgiform Headache with Conjunctival inJection and Tearing Syndrome with Intravenous Ketamine: A Case Report.

PURPOSE: 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. CASE REPORT: 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. CONCLUSION: 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.

Imaging peculiarities of gubernaculum tracts in molars as accessional teeth on CT.

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.

Changes in tonsillolith characteristics detected in a follow-up CT study.

BACKGROUND: Tonsilloliths are related clinically to halitosis and tonsillar abscess. However, the dynamics of tonsilloliths over time are unknown. The aim of the study was to evaluate change in the characteristics of tonsilloliths in a time-dependent fashion by follow-up computed tomography (CT). METHODS: Tonsilloliths were analyzed in 326 CT scan pair sets of initial and at least two follow-up CT examinations of patients with whole palatine tonsils and various diseases of the oral and maxillofacial regions. RESULTS: Over the follow-up period, 12.1% of tonsilloliths disappeared. Approximately 26.1% of tonsilloliths changed in size during follow-up, mostly increasing in size. In tonsilloliths that showed enlargement, the mean (± standard deviation) growth rate was 0.61 ± 0.41 mm per year. Approximately 37.3% of tonsilloliths changed position during the follow-up period; of these, movement was toward the respiratory tract in 92% at a mean rate of - 1.38 ± 1.59 mm per year. The calcification levels of almost all tonsilloliths showed dynamic change: HU number increased in 84.3% and decreased in 12.7% of tonsilloliths over the follow-up period. The mean rate of HU increase was 63.8 ± 96.3 HU/year, and the mean rate of HU decrease was - 38.4 ± 66.8 HU/year. CONCLUSIONS: The calcification levels of all tonsilloliths showed dynamic fluctuation, and a tendency for excretion of tonsilloliths from the body. Their dynamics over time suggest that tonsilloliths may be in a permanently active phase which functions to remove foreign matter.

A Nasal High-Flow System Prevents Upper Airway Obstruction and Hypoxia in Pediatric Dental Patients Under Intravenous Sedation.

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

First Report of Sublingual Gland Ducts: Visualization by Dynamic MR Sialography and Its Clinical Application.

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.

Effects of stellate ganglion block on postoperative trigeminal neuropathy after dental surgery: a propensity score matching analysis.

This study aimed to evaluate the effects of stellate ganglion block (SGB) on postoperative trigeminal neuropathy (TNP) after dental surgery. This was a retrospective study based on the medical records of all patients with postoperative TNP at Kyushu Dental University Hospital from 2014 to 2019. Patients were divided into the SGB group (received SGB) and non-SGB group (did not receive SGB). We evaluated the severity of TNP at 3 months after surgery and the incidence rate of abnormal sensations. Abnormal sensations were counted using patients' reports of uncomfortable symptoms during the treatment, including dysaesthesia, allodynia, and hyperalgesia. A propensity score (PS) matching analysis was performed to evaluate these data. After PS matching, amongst others, the force equivalent values of the Semmes-Weinstein test at 3-months post-treatment were significantly lower in the SGB group than in the non-SGB group (2.00 ± 0.44 vs 2.30 ± 0.48; p < 0.05). In addition, after PS matching, the incidence rate of abnormal sensations during the treatment was significantly lower in the SGB group than in the non-SGB group (10 cases [4.7%] vs 22 cases [10.3%]; p < 0.05). Collectively, the findings support that SGB may improve the recovery from postoperative TNP and reduce the incidence rate of abnormal sensations after dental surgery.

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.

The Reliability and Validity of the Japanese Version of the Modified Dental Anxiety Scale among Dental Outpatients.

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.

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.

Sedation With a Combination of Dexmedetomidine and Midazolam for Pediatric Dental Surgery.

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.

Prostanoid-dependent spontaneous pain and PAR2-dependent mechanical allodynia following oral mucosal trauma: involvement of TRPV1, TRPA1 and TRPV4.

Abstract: 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.

Anesthetic Management of a Patient With Takayasu Arteritis.

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.

Comparison of pain tolerance thresholds of upper limb to identify the most appropriate venipuncture site.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

A nasal high-flow system prevents hypoxia in dental patients under intravenous sedation.

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.

Distinct time courses of microglial and astrocytic hyperactivation and the glial contribution to pain hypersensitivity in a facial cancer model.

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.