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2.
J Pharmacol Exp Ther ; 368(1): 50-58, 2019 01.
Article in English | MEDLINE | ID: mdl-30409832

ABSTRACT

An injury of the somatosensory system causes neuropathic pain, which is usually refractory to conventional analgesics, thus warranting the development of novel drugs against this kind of pain. The mechanism of neuropathic pain in rats that had undergone left L5 spinal nerve transection was analyzed. Ten days after surgery, these rats acquired neuropathic pain. The patch-clamp technique was used on the isolated bilateral L5 dorsal root ganglion neurons. The current-clamped neurons on the ipsilateral side exhibited significantly higher excitability than those on the contralateral side. However, only neurons with diameters of 40-50 µm on the ipsilateral side exhibited significantly larger voltage sags in response to hyperpolarizing current pulses than those on the contralateral side. Under the voltage clamp, only these neurons on the ipsilateral side showed a significantly larger density of an inward current at < -80 mV [hyperpolarization-activated nonselective cation (I h) current] with a rightward-shifted activation curve than that on the contralateral side. Ivabradine-an I h current inhibitor-inhibited I h currents in these neurons on both sides in a similar concentration-dependent manner, with an IC50 value of ∼3 µM. Moreover, the oral administration of ivabradine significantly alleviated the neuropathic pain on the ipsilateral side. An inhibitor of adenylyl cyclase or an antagonist of prostanoid EP4 receptors (CJ-023423) inhibited ipsilateral, but not contralateral I h, currents in these neurons. Furthermore, the intrathecal administration of CJ-023423 significantly attenuated neuropathic pain on the ipsilateral side. Thus, ivabradine and/or CJ-023423 may be a lead compound for the development of novel therapeutics against neuropathic pain.


Subject(s)
Ganglia, Spinal/physiology , Neuralgia/physiopathology , Neurons/physiology , Receptors, Prostaglandin E, EP4 Subtype/physiology , Animals , Dose-Response Relationship, Drug , Ganglia, Spinal/drug effects , Injections, Spinal , Ivabradine/administration & dosage , Male , Membrane Potentials/drug effects , Membrane Potentials/physiology , Neuralgia/drug therapy , Neurons/drug effects , Organ Culture Techniques , Rats , Rats, Sprague-Dawley , Receptors, Prostaglandin E, EP4 Subtype/antagonists & inhibitors , Sulfonamides/administration & dosage
3.
Masui ; 65(8): 811-816, 2016 Sep.
Article in Japanese | MEDLINE | ID: mdl-30351592

ABSTRACT

BACKGROUND: Moyamoya disease (MD) is an occlu- sive cerebrovascular disease with risks of cerebral ischemia or hemorrhage. Although cesarean section (CS) is the prevailing delivery mode for these parturi- ents to stabilize cerebral circulation, the preferable mode remains controversial. We have conducted vagi- nal delivery with neuraxial analgesia (NA) because safety with the procedure is equivalent to that with CS. The aim of this study is to investigate peripartum outcomes, particularly delivery mode and occurrence of cerebrovascular events, in women with MD. METHODS: We retrospectively analyzed the data of parturients with MD for the previous 8 years. RESULTS: Among 13 pregnancies during this period, eight were vaginal deliveries with NA, while CS was executed in five cases according to obstetric indica- tions. Instrumental deliveries were conducted in five among eight vaginal delivery cases. No cerebrovascular event occurred during delivery. A transient ischemic attack in one case of vaginal delivery and cerebral ischemia in CS were noted in the postpartum period. CONCLUSIONS: We successfully managed vaginal deliveries in the eight patients with MD using NA. NA provides pain relief and assures maternal hemody- namic and respiratory stability during delivery. Instru- mental delivery plays a key role in reducing the dura- tion of the second stage of labor.


Subject(s)
Analgesia, Obstetrical , Moyamoya Disease , Pregnancy Complications, Cardiovascular , Adult , Cesarean Section/methods , Delivery, Obstetric , Female , Humans , Pregnancy , Retrospective Studies
4.
Masui ; 64(12): 1273-6, 2015 Dec.
Article in Japanese | MEDLINE | ID: mdl-26790332

ABSTRACT

A 39-year-old female with facioscapulohumeral muscular dystrophy (FSHD) was scheduled for thoracoscopic resection of an anterior mediastinal tumor. She had slowly progressive weakness and atrophy in the fascial and shoulder girdle muscles. General anesthesia was induced and maintained with propofol, remifentanil, and fentanyl combined with thoracic paravertebral block. Rocuronium-induced neuromuscular blockade was evaluated with acceleromyography at the corrugator supercilii, masseter, and adductor pollicis muscles. There was no reaction at the atrophic corrugator supercilii muscle in response to train-of-four (TOF) stimulation even before rocuronium administration. In contrast twitch responses at the masseter and adductor pollicis muscles to TOF stimulation could be evoked and the duration of action of rocuronium was found to be similar to that of the normal population. The perioperative course was uneventful. Neuromuscular monitoring sites should be carefully selected in FSHD patients because of possible inability to monitor neuromuscular function at the atrophic muscles.


Subject(s)
Androstanols/pharmacology , Anesthetics/pharmacology , Mediastinal Neoplasms/surgery , Muscular Dystrophy, Facioscapulohumeral/complications , Adult , Anesthesia, General , Facial Muscles , Female , Humans , Mediastinal Neoplasms/complications , Muscle, Skeletal/drug effects , Neuromuscular Blockade , Neuromuscular Monitoring , Rocuronium
5.
Masui ; 62(7): 859-62, 2013 Jul.
Article in Japanese | MEDLINE | ID: mdl-23905412

ABSTRACT

An emergency caesarean section was performed in a 38-year-old parturient with pregnancy-induced hypertension at week 31 of gestation because of nonreassuring fetal status. A chest X-ray revealed mild spinal scoliosis. We attempted a combined spinal-epidural anesthesia in the parturient because the Cobb angle was only 28 degrees. However, we failed to achieve epidural puncture at the T12-L1 and L1-2 interspaces using a paramedian approach. In addition, we failed to achieve the puncture of the subarachnoid spaces at L3-4 and L4-5 using medial and paramedian approaches. Finally, we succeeded in puncturing the subarachnoid space at L5-S1 using the median approach, and injected 11 mg of hyperbaric bupivacaine. Analgesia was achieved from the T6 to S regions, and the caesarean section was completed uneventfully. A postoperative X-ray and computed tomography scan revealed that the rotation of the lumbar spine was so severe that the spaces between the laminae of the lumbar regions were shifted to the left and narrowed. Therefore, the puncture of the epidural and subarachnoid spaces was difficult, suggesting that the degree of lumbar spine rotation is more important than the thoracic spine curvature for successful epidural and spinal anesthesia in parturients with scoliosis.


Subject(s)
Anesthesia, Epidural/methods , Anesthesia, Obstetrical/methods , Anesthesia, Spinal/methods , Cesarean Section , Pregnancy Complications , Scoliosis/complications , Adult , Emergencies , Female , Humans , Pregnancy
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