Masataka Kasahara

Expression of P2X₁ and P2X₄ receptors in rat trigeminal ganglion neurons.

Extracellular ATP, an essential pain mediator, is received by cell-surface ionotropic P2X and/or metabotropic P2Y receptors. Although the contribution of P2X3 and/or P2X2/3 receptors toward the pain mechanism is well described in trigeminal ganglion neurons, the expression of other subtypes of P2X receptor remains to be clarified. We examined expression of P2X receptor mRNA and measured intracellular free Ca2+ concentration ([Ca2+]i) by the activation of these receptors by fura-2 fluorescence in primary cultured rat trigeminal ganglion neurons. Real-time reverse transcription-PCR analysis revealed mRNA expression of P2X receptor subtype P2X1, P2X3, and P2X4 in trigeminal ganglion neurons. In the presence of extracellular Ca2+, the application of P2X receptors agonists, ATP, &agr;,&bgr;-methylene ATP or &bgr;,&ggr;-methylene ATP induced Ca2+ influx significantly. The ATP-induced increase in [Ca2+]i was inhibited by a series of selective antagonists for P2X1, P2X3, or P2X4 receptors. These results indicate that trigeminal ganglion neurons functionally express P2X1, P2X3, and P2X4 receptors and that these receptors are involved in the mediation of not only nociceptive but also neuropathic pain in the orofacial area.

Aminophylline reversal of prolonged postoperative sedation induced by propofol.

Propofol is frequently used for intravenous sedation or anesthesia in ambulatory and office-based anesthesia. Although awakening is usually rapid, there are instances of delayed recovery from propofol anesthesia. It has been reported that aminophylline antagonizes the sedative effects of several anesthetic and analgesic drugs. The case reports presented here demonstrate that intravenous aminophylline effectively reversed prolonged propofol-induced sedation/anesthesia in the postoperative period. There were no side effects or delayed re-sedation after the administration of aminophylline. Our study suggests that aminophylline could be a clinically useful propofol antagonist.

Pain-relieving effects of intravenous ATP in chronic intractable orofacial pain: an open-label study.

PurposeChronic orofacial pain is often refractory to conventional pain therapies. We conducted an open-label study to determine whether adenosine 5′-triphosphate (ATP) could alleviate chronic intractable orofacial pain, and if so, which type of pain could respond to ATP.MethodsIn 8 and 16 patients with non-neuropathic and neuropathic intractable orofacial pain, respectively, ATP was intravenously infused at a rate of 100 µg·kg−1·min−1 over 120 min. The magnitudes of spontaneous pain and brush-evoked allodynia were graded with a visual analog scale (VAS). When a VAS score for spontaneous pain was decreased by 50% or more by ATP, the patient was classified as a responder.ResultsThe patients could be clearly divided into 10 responders and 14 non-responders. Ten of the 16 patients (62.5%) with neuropathic pain, but none of the 8 patients with non-neuropathic pain, responded to ATP. In particular, all of 8 patients with neuropathic pain following pulpectomy, with or without subsequent tooth extraction, responded to ATP. In the 10 responders, VAS scores for spontaneous pain decreased slowly but progressively during the infusion period, and eventually, ATP reduced the VAS scores for spontaneous pain and allodynia by 82 ± 15% and 74 ± 9%, respectively. In these responders, the analgesic and anti-allodynic effects of ATP outlasted the infusion period for medians of 7 and 12 h, respectively.ConclusionIntravenous ATP did not relieve non-neuropathic orofacial pain. However, it exerted slowly expressed but long-lasting analgesic and anti-allodynic effects in patients with neuropathic orofacial pain, especially in those suffering from neuropathic pain following pulpectomy and/or tooth extraction.

Adenosine and amrinone reverse felypressin-induced depression of myocardial tissue oxygen tension in dogs.

Purpose: To determine whether continuous infusion of adenosine triphosphate (ATP), nitroglycerin (NTG) or amrinone (AM) would ameliorate the reductions in coronary blood flow (CBF) and myocardial oxygen tension (PmO2) induced by felypressin.Methods: Seven open-chest dogs were studied under urethane and alpha-chloralose anesthesia. Hemodynamic variables including heart rate (HR), systolic blood pressure, diastolic blood pressure (DBP), mean pulmonary artery pressure, pulmonary capillary wedge pressure, CBF (ultrasound flowmetry), PmO2 (polarography) and cardiac output (thermodilution method) were recorded. Felypressin was infused in a loading dose of 6 mlU·kg−1 for five minutes and then continued at 0.2 mlU·kg−1·min−1. After 30 min felypressin infusion, each agent was administered for 15 min to evaluate hemodynamic changes. Infusions were 100 and 200 µg·kg−1·min−1 for ATP, 2.5 and 5 µg·kg−1·min−1 for NTG, and 10 and 20 µg·kg−1·min−1 for AM.Results: After felypressin DBP increased by 17±5 (mean±SD) %; CBF decreased by 49±9%; Cl decreased by 40±13 %; HR decreased by 29±11 %; PmO2 in the inner layer decreased by 21±7%. The Cl and CBF returned to baseline after ATP 100 and 200 µg·kg−1·min−1, AM 10 and 20 µg·kg−1·min−1, but not after NTG. The PmO2 in the inner layer returned to the baseline value by any infusion except for NTG 5 µg·kg−1·min−1.Conclusion: Adenosine and amrinone, but not nitroglycerin reverses the adverse cardiovascular effects of felypressin.RésuméObjectif: Vérifier si une perfusion continue d’adénosine triphosphate (ATP), de nitroglycérine (NTG) ou d’amrinone (AM) améliore la réduction du débit coronarien (DC) et de la pression partielle en oxygène myocardique (PmO2) induits par la félypressine.Méthode: Sept chiens sous anesthésie avec uréthane et alpha-chloralose ont été étudiés à thorax ouvert. On a mesuré les variables hémodynamiques suivantes: la fréquence cardiaque (FC), la tension artérielle systolique (TAS), la tension artérielle diastolique (TAD), la tension artérielle pulmonaire moyenne, la tension capillaire pulmonaire, le DC (par ultrasonographie Doppler), la PmO2 (par polarographie) et le débit cardiaque en qualité d’index cardiaque IC (par thermodilution). La félypressine a été injectée en dose de charge de 6 mlU·kg−1 pendant cinq minutes, puis par une perfusion de 0,2 mlU·kg−1·min−1. Après 30 min, on a administré, pendant 15 min, une des perfusions de 100 et 200 µg·kg−1·min−1 d’ATP, 2,5 et 5 µg·kg−1·min−1 de NTG et 10 et 20 µg·kg−1·min−1 d’AM et on a évalué les changements hémodynamiques.Résultats: Après l’administration de félypressine, la TAD a augmenté de 17±5 (moyenne±écart type) %; le DC a diminué de 49±9 %; l’IC a baissé de 40±13 %; la FC a baissé de 29±11 %; la PmO2 a baissé de 21±7 % dans la couche interne. L’IC et le DC sont revenus aux mesures de base après l’administration de 100 et 200 µg·kg−1·min−1 d’ATP, 10 et 20 µg·kg−1·min−1 d’AM, mais non après la NTG. La PmO2 de la couche interne est revenue aux valeurs de base après toutes les perfusions, sauf après 5 µg·kg−1·min−1 de NTG.Conclusion: L’adénosine et l’amrinone, mais non la nitroglycérine, ont renversé les effets cardiovasculaires indésirables de la félypressine.

Unilateral Stellate Ganglion Block Produces Bidirectional Changes in Tissue Oxygen Tension of the Mental Nerve in Rabbits

PURPOSE The purpose of this study was to investigate changes in the tissue oxygen tension (PO(2)) of the mental nerve bilaterally before and after unilateral stellate ganglion block (SGB). MATERIALS AND METHODS Nine male Japan white rabbits were used. Anesthesia was maintained by a continuous infusion of propofol under mechanical ventilation with room air. For the SGB, the tip of a 26-gauge needle was placed on the left transverse process of the cervical vertebra; 0.2 mL of 1% lidocaine solution was injected. Data were recorded immediately before SGB and when the maximal change in PO(2) after SGB was observed. Observed variables were heart rate, blood pressure, common carotid arterial blood flow, tongue mucosal blood flow, left PO(2), and right PO(2). RESULTS PO(2) showed maximal changes 7.9 ± 2.0 minutes after SGB. No changes were observed in heart rate and blood pressure after SGB. Common carotid arterial blood flow, tongue mucosal blood flow, and left PO(2) were increased by 106.4% ± 39.8%, 36.2% ± 35.2%, and 38.7% ± 19.8%, respectively, after SGB. In contrast, right PO(2) was decreased by 29.8% ± 7.4% after SGB. CONCLUSIONS These results suggest that unilateral SGB produces bidirectional changes in the PO(2) of the mental nerve and that SGB decreases the PO(2) of the mental nerve on the contralateral side.

Effect of changes in end‐tidal carbon dioxide tension on oral tissue blood flow during dexmedetomidine infusion in rabbits

A decrease in arterial carbon dioxide tension induces an increase in masseter muscle blood flow and a decrease in mandibular bone marrow blood flow during general anesthesia. In addition, dexmedetomidine infusion reduces oral tissue blood flow. In this study we investigated how end-tidal carbon dioxide tension (ET-CO2 ) changes influence on oral tissue blood flow during continuous dexmedetomidine infusion in rabbits. Eleven male Japan White rabbits were anesthetized with sevoflurane. Then, ET-CO2 was set at 30 mmHg and adjusted to 40 and 60 mmHg, and heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure, common carotid artery blood flow, mandibular bone marrow blood flow, masseter muscle blood flow, and blood flow in other oral tissues were measured. Following this, the ET-CO2 was returned to 30 mmHg and dexmedetomidine was infused over 60 min. The measurements were repeated. Most parameters increased, regardless of whether or not dexmedetomidine was present, and heart rate and masseter muscle blood flow decreased in an ET-CO2 -dependent manner. Dexmedetomidine infusion suppressed ET-CO2 -dependent masseter muscle blood flow change. Masseter muscle blood flow during ET-CO2 at 30 mmHg with dexmedetomidine was the same as that during ET-CO2 at 40 mmHg without dexmedetomidine. Our findings suggest that dexmedetomidine infusion and slight hypocapnia under general anesthesia suppress an increase in masseter muscle blood flow as well as reducing mandibular bone marrow blood flow. These results may be of significance for decreasing bleeding during oral and maxillofacial surgery.

Remifentanil decreases oral tissue blood flow while maintaining internal carotid artery blood flow during sevoflurane anesthesia in rabbits

The aim of this study was to investigate the effect of remifentanil infusion on oral tissue blood flow including submandibular gland tissue blood flow (SBF) and internal carotid artery blood flow (ICBF) in rabbits during sevoflurane anesthesia. Twelve male Japan White rabbits were anesthetized with sevoflurane and remifentanil. Remifentanil was infused at 0.2 and 0.4 µg/kg/min. Measurements included circulatory variables, common and external carotid artery blood flow (CCBF, ECBF), ICBF, tongue mucosal blood flow (TMBF), masseter muscle tissue blood flow (MBF), mandibular bone marrow tissue blood flow (BBF), tongue muscle tissue blood flow (TBF) and SBF. Vascular resistances for each tissue, including the tongue mucosa, masseter muscle, mandibular bone marrow, tongue muscle and submandibular gland, were calculated by dividing the mean arterial pressure by the respective tissue blood flow. Remifentanil infusion decreased oral tissue blood flow and circulatory variables. CCBF, ECBF and ICBF did not change. The calculated vascular resistance in each oral tissue, except for the tongue mucosa, increased in an infusion-rate-dependent manner. These results showed that remifentanil infusion reduced TMBF, MBF, BBF, TBF and SBF in an infusion-rate-dependent manner without affecting ICBF under sevoflurane anesthesia.

Influence of lyophilization factors and gelatin concentration on pore structures of atelocollagen/gelatin sponge biomaterial

This study aimed to investigate influences of lyophilization factors and gelatin concentration on pore structures of ACG sponge. ACG sponges of different freezing temperatures (-30, -80 and -196oC), freezing times (1, 2 and 24 h), gelatin concentrations (0.6%AC+0.15%G, 0.6%AC+0.6%G and 0.6%AC+2.4%G), and with 500 μM fluvastatin were fabricated. Pore structures including porosity and pore size were analyzed by scanning electron microscopy and ImageJ. The cytotoxic effects of ACG sponges were evaluated in vitro. Freezing temperature did not affect porosity while high freezing temperature (-30oC) increased pore size. The high gelatin concentration group (0.6%AC+2.4%G) had decreased porosity and pore size. Freezing time and 500 μM fluvastatin did not affect pore structures. The cytotoxicity and cell proliferation assays revealed that ACG sponges had no cytotoxic effects on human mesenchymal stromal cell growth and proliferation. These results indicate that ACG sponge may be a good biomaterial scaffold for bone regeneration.

Continuous postoperative pain control using a multiple-hole catheter after iliac bone grafting: comparison between ropivacaine and levobupivacaine.

The aim of this study was to compare the analgesic effects of ropivacaine and levobupivacaine in continuous infiltration anaesthesia delivered via a multiple-hole catheter for the purpose of postoperative analgesia after iliac bone grafting. Thirty-four patients scheduled for iliac bone grafting in the maxillofacial region participated in this study. The patients were randomized to a ropivacaine group (Ropi group) and a levobupivacaine group (Levo group). After harvesting the iliac bone for grafting, a multiple-hole catheter was placed on the periosteum of the iliac bone. When surgery was completed, continuous administration was started at 4 ml/h of 0.2% ropivacaine (Ropi group) or 0.25% levobupivacaine (Levo group). Pain was evaluated in the recovery room and at 4h after surgery, as well as at 9:00 and 18:00 on postoperative days 1, 2, and 3, using a visual analogue scale. Side effects were also recorded. No significant difference in the visual analogue scale scores at rest or in motion was observed between the two groups. In addition, there were no side effects in the two groups. Both 0.2% ropivacaine and 0.25% levobupivacaine provided comparable analgesic effects in continuous infiltration anaesthesia delivered via a multiple-hole catheter after iliac bone grafting.

Effect of Topical Anesthesia Using an Adhesive Patch and Anesthetic Solution

&NA; We analyzed trigeminal somatosensory evoked potentials (TSEP) to the alveolar mucosa to investigate the efficacy of an amide local anesthetic, 2% lidocaine hydrochloride with 12.5 &mgr;g/mL epinephrine (Lido treatment) as a topical anesthetic. Eighteen consenting healthy adult volunteers were enrolled. A volume of 0.06 mL of Lido, 0.06 g of 20% benzocaine, or 0.06 mL of physiological saline (control) was instilled onto a hemostatic adhesive patch, which was then applied to the alveolar mucosa at the maxillary right canine for 5 minutes. An electrical stimulus approximately 5 times that of the sensory threshold was applied using a surface stimulation electrode. The trigeminal somatosensory evoked potential was recorded immediately, 5 minutes, and 10 minutes after removal of the patch. Positive P125 and P310 peaks and negative N100 and N340 peaks were observed as a result of the electrical stimulation. A significant decrease in the percentage change in amplitude of N100‐P125 was observed in the Lido treatment immediately, 5 minutes, and 10 minutes after patch removal. In the Lido treatment, trigeminal somatosensory evoked potential amplitude at N100‐P125 decreased significantly, suggesting that topical anesthesia produced by an amide local anesthetic may have a topical anesthetic effect as potent as that produced by an ester local anesthetic.