Aiko Oyamaguchi

Trigeminal nervous system sensitization by infraorbital nerve injury enhances responses in a migraine model

Background Although the peripheral and central sensitizations of trigeminal nervous system may be one of the important factors of migraine, the precise mechanism is not fully understood. In this study, we examined the influence of the sensitization of the second division of the trigeminal nerve (V2) by chronic constriction injury (CCI) of the infraorbital nerve (ION) on migraine headache, using the capsaicin-induced migraine model. Methods Male Sprague-Dawley rats were assigned to four groups: (a) sham surgery and topical-dural vehicle application (Sham + Vehicle) group, (b) CCI-ION and topical-dural vehicle application (CCI-ION + Vehicle) group, (c) sham surgery and topical-dural capsaicin application (Sham + Capsaicin) group, (d) CCI-ION and topical-dural capsaicin application (CCI-ION + Capsaicin) group. Behavioral testing and immunohistochemical staining were performed. Results In the behavioral test, the Sham + Capsaicin group showed significantly longer duration of immobilization and shorter duration of exploration compared with the Sham + Vehicle group, which is similar to clinical features of migraine patients. Moreover, CCI-ION enhanced these effects in the CCI-ION + Capsaicin group. Immunohistochemical staining for phospho-extracellular signal-related kinase (pERK) in the trigeminal ganglion (TG) containing first and second divisions of the trigeminal nerve and the trigeminocervical complex (TCC) revealed that pERK expression was significantly increased in the CCI-ION + Capsaicin group compared with the other groups. However, comparing between effects of the peripheral and central sensitizations (in the TG and TCC), from our results, peripheral sensitization would play a much less or not significant role. Conclusions These data demonstrate that the sensitization of V2 could influence the activation and the sensitization of the first division of the trigeminal nerve in the TCC, subsequently exacerbating pain sensation and pain-related behaviors. We have shown for the first time that the existence of the central sensitization of V2 can be an exacerbating factor for migraine related nociceptive thresholds/activation.

Effectiveness of dexmedetomidine for emergence agitation in infants undergoing palatoplasty: a randomized controlled trial

OBJECTIVES In infants, there is a high incidence of emergence agitation (EA) after sevoflurane (Sev) anesthesia. This study aimed to test the hypothesis that dexmedetomidine (Dex) administration would reduce the incidence and severity of EA after Sev-based anesthesia in infants undergoing palatoplasty. METHODS A prospective randomized clinical trial was conducted with 70 patients undergoing palatoplasty, aged 10-14 months. Infants were randomly allocated into two groups: Dex (n=35) and saline (n=35). In the Dex group, Dex (6 μg/kg/h) was administered approximately 10 min before the end of the surgery for 10 min, followed by 0.4 μg/kg/h until 5 min after extubation. In the saline group, an equivalent amount of saline was administered in a similar manner. After the surgery, patients were transferred to the postanesthetic care unit (PACU). The infants behavior and pain were assessed with scoring system for EA (5-point rating scale) and pain scale (PS; 10-point rating scale), respectively. EA and PS were estimated at six time points (after extubation, leaving the operating room, 0, 30, 60, and 120 min after arrival in PACU). RESULTS EA and PS scores were significantly lower in the Dex group than in the saline group from extubation to 120 min after arrival in PACU. CONCLUSIONS Dex administration has the advantage of a reduced EA and PS without any adverse effects. Dex provided satisfactory recovery in infants undergoing palatoplasty.

Selective elimination of isolectin B4-binding trigeminal neurons enhanced formalin-induced nocifensive behavior in the upper lip of rats and c-Fos expression in the trigeminal subnucleus caudalis

The functional significance of non-peptidergic C-fibers in orofacial pain processing is largely unknown. The present study examined the effects of the selective elimination of isolectin B4 (IB4)-binding (IB4(+)) neurons on formalin-induced face rubbing behavior (FRB) in the upper lip of rats and c-Fos-immunoreactive (c-Fos-IR) cells in the trigeminal subnucleus caudalis (Vc). IB4 conjugated to neurotoxin, saporin (IB4-Sap), blank-saporin (Bl-Sap), or saline (Sal) was injected into the cisterna magna. IB4-Sap treatments significantly decreased IB4(+) terminals in lamina II of Vc and IB4(+) trigeminal ganglia neurons, whereas Sal- and BI-Sap treatments did not. The number of formalin-induced FRB 15-30 min after the formalin injection was significantly higher in IB4-Sap-treated rats than in Sal- or Bl-Sap-treated rats, and was associated with an increase in c-Fos-IR cells. The systemic preadministration of the GABAA antagonist, bicuculline, and agonist, muscimol, had stronger decreasing effects on FRB and c-Fos-IR cells in IB4-Sap-treated rats than the preadministration of Sal, whereas the opposite effects were observed in Sal- and Bl-Sap-treated rats. These results indicate that IB4(+) neurons in the trigeminal nerve play antinociceptive regulatory roles in formalin-induced orofacial pain processing and that GABAA receptor functions at segmental and supratrigeminal sites have complex modulatory influences on antinociceptive roles.

Effective Dosage of Midazolam to Erase the Memory of Vascular Pain During Propofol Administration

Intravenous sedation with propofol is often administered to anxious patients in dental practice. Pain on injection of propofol is a common adverse effect. This study aimed to determine the age-adjusted doses of midazolam required to erase memory of vascular pain of propofol administration and assess whether the Ramsay Sedation Scale (RSS) after the pretreatment of midazolam was useful to predict amnesia of the vascular pain of propofol administration. A total of 246 patients with dental phobia requiring dental treatment under intravenous sedation were included. Patients were classified according to their age: 30s, 40s, 50s, and 60s. Three minutes after administration of a predetermined dose of midazolam, propofol was infused continuously. After completion of the dental procedure, patients were interviewed about the memory of any pain or discomfort in the injection site or forearm. The dosage of midazolam was determined using the Dixon up-down method. The first patient was administered 0.03 mg/kg, and if memory of vascular pain remained, the dosage was increased by 0.01 mg/kg for the next patient, and then if the memory was erased, the dosage was decreased by 0.01 mg/kg. The effective dosage of midazolam in 95% of each age group for erasing the memory of propofol vascular pain (ED95) was determined using logistic analysis. The accuracy of RSS to predict the amnesia of injection pain was assessed by receiver operating characteristic (ROC) analysis. The ED95 of midazolam to erase the memory of propofol vascular pain was 0.061 mg/kg in patients in their 30s, 0.049 mg/kg in patients in their 40s, 0.033 mg/kg in patients in their 50s, and 0.033 mg/kg in patients in their 60s. The area under the ROC curve was 0.31. The ED95 of midazolam required to erase the memory of propofol vascular pain demonstrated a downward trend with age. On the other hand, it was impossible to predict the amnesia of propofol vascular pain using the RSS.

Premedication with midazolam in intellectually disabled dental patients: Intramuscular or oral administration? A retrospective study

Background The use of midazolam for dental care in patients with intellectual disability is poorly documented. The purpose of this study was to determine which method of premedication is more effective for these patients, 0.15 mg/kg of intramuscular midazolam or 0.3 mg/kg of oral midazolam. Material and Methods This study was designed and implemented as a non-randomized retrospective study. The study population was composed of patients with intellectual disability who required dental treatment under ambulatory general anesthesia from August 2009 through April 2013. Patients were administered 0.15 mg/kg of midazolam intramuscularly (Group IM) or 0.3 mg/kg orally (Group PO). The predictor variable was the method of midazolam administration. The outcome variables measured were Observer’s Assessment of Alertness/ Sedation (OAA/S) Scale scores, the level of cooperation when entering the operation room and for venous cannulation, post-anesthetic agitation and recovery time. Results Midazolam was administered intramuscularly in 23 patients and orally in 21 patients. More patients were successfully sedated with no resistance behavior during venous cannulation in Group PO than in Group IM (p=0.034). There were no differences in demographic data and other variables between the groups. Conclusions The results of this study suggest that oral premedication with 0.3 mg/kg of midazolam is more effective than 0.15 mg/kg of midazolam administered intramuscularly, in terms of patient resistance to venous cannulation. If both oral and intramuscular routes of midazolam are acceptable in intellectually disabled patients, the oral route is recommended. Key words:Premedication, midazolam, intellectual disability.