Shunji Shiiba

Central glial activation mediates cancer-induced pain in a rat facial cancer 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.

Endothelin Receptor-mediated Responses in Trigeminal Ganglion Neurons

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.

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.

Relationship between the curative effects of carbamazepine administration and the neurovascular compression volume of the trigeminal nerve measured using magnetic resonance cisternography.

ObjectivesTo elucidate the relationship between the extent of pain and neurovascular compression (NVC) volume, measured by magnetic resonance (MR) cisternography, in patients with trigeminal neuralgia. In addition, we aimed to evaluate the relationship between NVC volume and the efficacy of carbamazepine administration in patients with trigeminal neuralgia. MethodsMR cisternography was performed on 214 patients with clinical signs and symptoms that suggested trigeminal neuralgia retrospectively. The extent of their pain was evaluated using visual analog scales. Next, only carbamazepine was administered as the initial treatment. For the patients with NVC detectable on MR cisternography, the relationship between the extent or nature of the pain and the neurovascular volume was analyzed. In addition, the correlation between the efficacy of carbamazepine treatment and the NVC volume was evaluated retrospectively. ResultsOf the 214 patients evaluated, 144 were deemed to have NVC. In these 144 patients, a significant difference was found between the NVC volume and the curative effects of 100 mg/d carbamazepine. However, no significant correlation was found between the extents of pain by visual analog score or between the daily dosage of carbamazepine and the NVC volume measured by MR cisternography. ConclusionsThree-dimensional MR cisternography is very useful for detecting the site of NVC in patients with trigeminal neuralgia. NVC measured by this technique may indicate the prognosis after initial treatment. The present results suggest that the evaluation of NVC volume by MR cisternography would be useful in choosing the initial treatment for patients with trigeminal neuralgia.

Diagnostic significance of characteristic findings on ultrasonography for the stitch abscess after surgery in patients with oral squamous cell carcinoma

To elucidate the clinical significance of imaging modalities for detection of stitch abscess after surgery in patients with oral squamous cell carcinoma (SCC). In 137 patients with oral SCC suspected of having lymph node metastases, local recurrence of tumor, or stitch abscess after surgery, the characteristic imaging findings related to lymph node metastases, local recurrence of tumor, and stitch abscess on ultrasonography (US), computed tomography (CT), magnetic resonance (MR), and (18)fluorodeoxyglucose (18FDG)-positron emission tomography (PET) images were identified and analyzed. In all six patients with stitch abscess, characteristic findings were demonstrated on US, different from those of metastatic lymph nodes and local recurrence on CT, MRI, and 18FDG-PET images. Our results suggest that ultrasonography may be a very useful tool for diagnosis of postoperative stitch abscess and may help improve the quality of life of oral SCC patients.

Non-randomized controlled prospective study on perioperative levels of stress and dysautonomia during dental implant surgery

PURPOSE The purpose of this study was to compare pre- and postoperative autonomic activities and changes in salivary stress biomarkers between patients who received only local anesthesia and those who received local anesthesia together with intravenous sedation in dental implant surgery. METHODS A total of 21 patients were enrolled in this non-randomized controlled prospective study; 7 subjects underwent implant surgery under local anesthesia with intravenous sedation and 14 subjects underwent surgery under only local anesthesia. Stress was evaluated by measuring salivary levels of chromogranin A (CgA) and a spectral analysis of heart rate variability (HRV) at baseline (on a day other than the day of surgery), 1h preoperatively, and 1h postoperatively. HRV analysis yields low- (LF) and high-frequency (HF) components, the LF/HF ratio, and the component coefficient of variance (CCV[HF]), which provide indices of sympathetic and parasympathetic regulatory activity. RESULTS CgA levels were significantly higher (p<0.05) at baseline in patients who received sedation than those who did not, but CgA levels did not differ prior to surgery. Also, the values of most parameters, including LF, HF, LF/HF (L/H), and CCV(HF), did not significantly differ between groups or among the three time points. Only ΔL/H and ΔCCV(HF) were significantly lower (p<0.05) at 1h preoperatively in patients who received sedation than those who received only local anesthesia. CONCLUSIONS CgA levels were high in both groups immediately before surgery, and thus CgA values immediately before surgery may not be a reliable indicator of the need for intravenous sedation. Also, spectral analysis of HRV, especially ΔL/H and ΔCCV(HF), could be useful for assessing tension and anxiety.

A Possible Case of Complex Regional Pain Syndrome in the Orofacial Region

OBJECTIVE To present a case of complex regional pain syndrome (CRPS) type II with sympathetic dysfunction and trophic changes in the orofacial region, which was partially responsive to intravenous ketamine. PATIENT The patient was a 68-year-old man who suffered from inveterate pain with trophic changes of the right face and tongue and vasomotor dysfunction on the right side of the face after ipsilateral trigeminal nerve block. Allodynia and hyperalgesia were observed on the affected side of the face. Pain initially improved after sympathetic nerve block, but similar pain returned that was unresponsive to the same procedure. Repeated intravenous administration of low-dose ketamine preceded by intravenous midazolam alleviated the pain, but trophic changes of the tongue persisted. DISCUSSION CRPS in the orofacial region has not been clearly defined and has been infrequently documented. Clinical findings in this patient met the criteria of the International Association for the Study of Pains and Hardens diagnostic criteria for CRPS. The reason for gradual pain relief after induction of intravenous ketamine therapy was unclear, but the fact that only ketamine and not other various pain medicines or procedures alleviated the pain is important to note. CONCLUSION Distinct cases of CRPS involving the orofacial region are rare. Thorough observations and documentation of signs and symptoms may lead to future standardization of diagnostic criteria and treatment strategies for this disorder.

Noninvasive identification of peripheral vessels of oral and maxillofacial regions by using electrocardiography-triggered three-dimensional fast asymmetric spin-echo sequences.

OBJECTIVES The aim of this study was to evaluate the 3-dimensional images of thinner main peripheral vessels in oral and maxillofacial regions made without contrast medium by using a new technique, fresh blood imaging (FBI). A second objective was to discern arteries from veins by using the combination of FBI with the subtraction technique. STUDY DESIGN Images from FBI were compared with those from 3-dimensional phase-contrast magnetic resonance angiography (MRA) of blood vessels in 20 healthy subjects. All images were scored for visualization and image quality of the main blood vessels. In addition, appropriate flow-spoiled gradient pulses were applied to differentiate arteries from veins in the peripheral vasculature using a combination of FBI sequences and subtraction between systole- and diastole-triggered images. RESULTS The scores of MRA using FBI for the visualization of thin blood vessels were significantly better than those using phase contrast, whereas scores for the visualization of main blood vessels were equal. Additionally, we succeeded in our initial attempt to differentiate arteries from veins with a reasonable acquisition time. CONCLUSIONS Our initial experience shows that FBI could be a useful method to identify 3-dimensional vasculature and to differentiate arteries from veins among thinner peripheral vessels in the oral and maxillofacial regions without using contrast medium.

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.

Evaluation of the Treatment Modalities for Neurosensory Disturbances of the Inferior Alveolar Nerve Following Retromolar Bone Harvesting for Bone Augmentation

SUBJECTS The purpose of this study was to evaluate the treatment modalities for neurosensory disturbances (NSDs) of the inferior alveolar nerve occurring after retromolar bone harvesting for bone augmentation procedures before implant placement. METHODS One hundred four patients, of which 49 and 55 exhibited vertical or horizontal alveolar ridge defects in the mandible and maxilla, respectively, were enrolled. Nineteen patients underwent block bone grafting, 38 underwent guided bone generation or autogenous bone grafting combined with titanium mesh reconstruction, and 47 underwent sinus floor augmentation. Using a visual analog scale, we examined subjective symptoms and discomfort related to sensory alteration within the area of the NSDs in these patients. NSDs were clinically investigated using a two-point discrimination test with blunt-tipped calipers. In addition, neurometry was used for evaluation of trigeminal nerve injury. We tested three treatment modalities for NSDs: follow-up observation (no treatment), medication, and stellate ganglion block (SGB). RESULTS A week after surgery, 26 patients (25.0%) experienced NSDs. Five patients received no treatment, 10 patients received medication, and 11 patients received SGB. Three months after surgery, patients in the medication and SGB group achieved complete recovery. Current perception threshold values recovered to near-baseline values at 3 months: recovery was much earlier in this group than in the other two groups. SGB can accelerate recovery from NSDs. CONCLUSIONS Our results justify SGB as a reasonable treatment modality for NSDs occurring after the harvesting of retromolar bone grafts.