Effect of carbamazepine and gabapentin on excitability in the trigeminal subnucleus caudalis of neonatal rats using a voltage-sensitive dye imaging technique

BACKGROUND: The antiepileptic drugs carbamazepine and gabapentin are effective in treating neuropathic pain and trigeminal neuralgia. In the present study, to analyze the effects of carbamazepine and gabapentin on neuronal excitation in the spinal trigeminal subnucleus caudalis (Sp5c) in the medulla oblongata, we recorded temporal changes in nociceptive afferent activity in the Sp5c of trigeminal nerve-attached brainstem slices of neonatal rats using a voltage-sensitive dye imaging technique. RESULTS: Electrical stimulation of the trigeminal nerve rootlet evoked changes in the fluorescence intensity of dye in the Sp5c. The optical signals were composed of two phases, a fast component with a sharp peak followed by a long-lasting component with a period of more than 500 ms. This evoked excitation was not influenced by administration of carbamazepine (10, 100 and 1,000 µM) or gabapentin (1 and 10 µM), but was increased by administration of 100 µM gabapentin. This evoked excitation was increased further in low Mg²+ (0.8 mM) conditions, and this effect of low Mg²+ concentration was antagonized by 30 µM DL-2-amino-5-phosphonopentanoic acid (AP5), a N-methyl-D-as-partate (NMDA) receptor blocker. The increased excitation in low Mg²+ conditions was also antagonized by carbamazepine (1,000 µM) and gabapentin (100 µM). CONCLUSION: Carbamazepine and gabapentin did not decrease electrically evoked excitation in the Sp5c in control conditions. Further excitation in low Mg²+ conditions was antagonized by the NMDA receptor blocker AP5. Carbamazepine and gabapentin had similar effects to AP5 on evoked excitation in the Sp5c in low Mg²+ conditions. Thus, we concluded that carbamazepine and gabapentin may act by blocking NMDA receptors in the Sp5c, which contributes to its anti-hypersensitivity in neuropathic pain.

Upper airway obstruction associated with flexed cervical position after posterior occipitocervical fusion.

Upper airway obstruction resulting from overflexion fixation of the cervical spine is a rare but life-threatening complication after cervical spine surgery. There are few reports of dyspnea after a posterior cervical fusion. We present the case of a 63-year-old woman with rheumatoid arthritis who developed an upper airway obstruction immediately after an O-C4 fusion. She was reintubated with a fiberoptic scope. Revision surgery allowing the angle to return to the neutral position was performed to ameliorate the overflexion of the cervical spine fixation and the consequent upper airway obstruction. After revision surgery, the upper airway obstruction disappeared. Our experience suggests that intraoperative use of fluoroscopy and extubation with a tube exchanger are recommended to avoid this complication, especially in patients at high risk of upper airway obstruction.

Application of gum elastic bougie to nasal intubation.

Gum elastic bougie (GEB), a useful device for difficult airway management, has seldom been used for nasotracheal intubation. Among 632 patients undergoing dental procedures or oral surgery, GEB was used successfully in 16 patients in whom conventional nasal intubation had failed because of anatomical problems or maldirection of the tip of the tracheal tube. We recommend that GEB should be applied from the first attempt for nasal intubation in patients with difficult airways.

[Pulmonary edema due to laryngospasm immediately after extubation].

We describe a case of negative pressure pulmonary edema (NPPE) followed by laryngospasm occurred immediately after extubation. A 56-year-old man with a tumor at the site of ureteroneocystostomy underwent left ureterectomy and partial resection of the neobladder under general anesthesia. The tracheal intubation was difficult with glade 3 of Cormack classification. Anesthesia was maintained with sevoflurane, nitrous oxide, and oxygen. After fully awake extubation, the upper airway obstruction due to laryngospasm was observed. A nasal airway was inserted, but face mask ventilation was impossible. Ventilation became possible with SpO2 of around 40%, and spontaneous respiration appeared. The patient was nasally intubated with a fiberoptic bronchoscope. Furosemide was administered in ICU and mechanical ventilation with 5cmH2O PEEP was started. Seventeen hours later, the pulmonary edema disappeared and he was successfully extubated without any complications. It was warned that laryngospasm would occur even after the full emergence, leading to NPPE.

Donepezil reverses buprenorphine-induced central respiratory depression in anesthetized rabbits

Buprenorphine is a mixed opioid receptor agonist-antagonist used in acute and chronic pain management. Although this agent's analgesic effect increases in a dose-dependent manner, buprenorphine-induced respiratory depression shows a marked ceiling effect at higher doses, which is considered to be an indicator of safety. Nevertheless, cases of overdose mortality or severe respiratory depression associated with buprenorphine use have been reported. Naloxone can reverse buprenorphine-induced respiratory depression, but is slow-acting and unstable, meaning that new drug candidates able to specifically antagonize buprenorphine-induced respiratory depression are needed in order to enable maximal analgesic effect without respiratory depression. Acetylcholine is an excitatory neurotransmitter in central respiratory control. We previously showed that a long-acting acetylcholinesterase inhibitor, donepezil, antagonizes morphine-induced respiratory depression. We have now investigated how donepezil affects buprenorphine-induced respiratory depression in anesthetized, paralyzed, and artificially ventilated rabbits. We measured phrenic nerve discharge as an Índex of respiratory rate and amplitude, and compared discharges following the injection of buprenorphine with discharges following the injection of donepezil. Buprenorphine-induced suppression of the respiratory rate and respiratory amplitude was antagonized by donepezil (78.4 ± 4.8 percent, 92.3 percent ± 22.8 percent of control, respectively). These findings indicate that systemically administered donepezil restores buprenorphine-induced respiratory depression in anesthetized rabbits.

Perioperative management of obstructive sleep apnea with nasal continuous positive airway pressure.

The high risks associated with general anesthesia in obstructive sleep apnea syndrome (OSAS) patients have been reported. Many authors have suggested that the intraoperative administration of opioids and sedatives should be limited or avoided because these drugs selectively impair muscle activity in the upper airway. We report the case of an OSAS patient who was managed with nasal continuous positive airway pressure (NCPAP) and treated safely in spite of the use of conventional anesthetic and analgesic agents typically used for patients without OSAS. She had little pain during the perioperative period. It is suggested that NCPAP is an effective treatment for not only preventing airway obstructive apnea but for allowing the administration of anesthetic and analgesic drugs without major complications.

Application of nasal flexible laryngeal mask airway in anesthesia for oral surgery.

The laryngeal mask airway has been used increasingly in clinics but is seldom applied in anesthesia for oral surgery, as the mask occupies the middle of the mouth and tends to obstruct the surgical field. Here, we report the successful placement and usage of a nasal flexible laryngeal mask airway (FLMA) in an oral surgical procedure. Fifteen patients undergoing dental procedures under general anesthesia were studied. We clinically applied a previously reported method for inserting an FLMA with some modifications. There was no significant bleeding from the intubated nostril in any of the patients. None of the patients complained of sore throat, coughing, hoarseness, or any discomfort in the nose. Although we anticipate that further refinements of the technique may be possible and that the safety of this method using a nasal FLMA needs to be assessed in a greater number of patients, in this preliminary study we provide a proof-of-principle demonstration of the efficacy of nasal LMA ventilation as a method of airway management for oral surgery.

Archaeal-type rhodopsins in Chlamydomonas: model structure and intracellular localization.

Phototaxis in the unicellular green alga Chlamydomonas reinhardtii is mediated by rhodopsin-type photoreceptor(s). Recent expressed sequence tag database from the Kazusa DNA Research Institute has provided the basis for unequivocal identification of two archaeal-type rhodopsins in it. Here we demonstrate that one is located near the eyespot, wherein the photoreceptor(s) has long been thought to be enriched, along with the results of bioinformatic analyses. Secondary structure prediction showed that the second putative transmembrane helices (helix B) of these rhodopsins are rich in glutamate residues, and homology modeling suggested that some additional intra- or intermolecular interactions are necessary for opsin-like folding of the N-terminal ca. 300-aa membrane spanning domains of 712 and 737-aa polypeptides. These results complement physiological and electrophysiological experiments combined with the manipulation of their expression [O.A. Sineshchekov, K.H. Jung, J.H. Spudich, Proc. Natl. Sci. USA 99 (2002) 8689; G. Nagel, D. Olig, M. Fuhrmann, S. Kateriya, A.M. Musti, E. Bamberg, P. Hegemann, Science 296 (2002) 2395].