Antinociceptive effect of intracerebroventricular administration of glycine transporter-2 inhibitor ALX1393 in rat models of inflammatory and neuropathic pain.

Glycinergic transmission has an important role in regulating nociception in the spinal cord. The glycine transporter-2 (GlyT2) is localized at presynaptic terminals of glycinergic neurons and eliminates glycine from the synaptic cleft to terminate glycinergic transmission. Systemic and intrathecal administration of GlyT2 inhibitors alleviate various types of pain. Although the GlyT2s and glycine receptors are widely distributed in the central nervous system, little is known about the role of glycinergic transmission in pain perception at supraspinal regions. The present study examined the antinociceptive effect of intracerebroventricular (i.c.v.) administration of the selective GlyT2 inhibitor ALX1393 on inflammatory and neuropathic pain in experimental models. For i.c.v. administration, a guide cannula was implanted into the right lateral ventricle of male Sprague-Dawley rats. Normal rats were used to assess inflammatory nociception using the formalin test and motor function using the rotarod test. Chronic constriction injury (CCI) to the sciatic nerve was induced in the rats. The CCI rats were then used to assess mechanical, cold, and thermal hyperalgesia using the electronic von Frey test, cold plate test, and the plantar test, respectively. ALX1393 (25, 50, and 100 µg) was administered i.c.v. to examine its effects on supraspinal antinociception. Supraspinal ALX1393 in normal rats suppressed the late-phase response in the formalin test but did not affect motor performance. In the CCI rats, ALX1393 inhibited mechanical and cold hyperalgesia in a dose-dependent manner. The antihyperalgesic effects of ALX1393 (100 µg) were reversed completely by i.c.v. pretreatment with a glycine receptor antagonist strychnine (10 µg). These results suggest that GlyT2 contributes to nociceptive transmission at supraspinal level and that the selective GlyT2 inhibitor is a promising candidate for the treatment of inflammatory and neuropathic pain without causing motor dysfunction.

[A Case of General Anesthesia in a Patient with Spinal and Bulbar Muscular Atrophy].

We report a successful management of anesthesia in a 55-year-old male patient with spinal and bulbar muscular atrophy (SBMA). His respiratory and swallowing functions were preserved preoperatively. He underwent an osteosynthesis for a femoral neck fracture under general anesthesia using nondepolarizing muscle relaxant. The anesthetic concerns in patients with SBMA are the possibility of postoperative respiratory dysfunction due to anesthetics or muscle relaxants and that of postoperative neurological deterioration due to spinal or epidural anesthesia. In this case, the effect of an intubating dose of rocuronium (0.5 mg · kg(-1)) was markedly prolonged, but it was completely reversed by sugammadex (2 mg · kg(-1)). Postoperative course was uneventful and clinical symptoms of SBMA did not become exacerbated.

[Anesthetic considerations for thymectomy in a patient having an anti-acetylcholine receptor antibody without myasthenia gravis].

A patient having an anti-acetylcholine receptor (AChR) antibody without myasthenia gravis was scheduled for thymectomy. Neuromuscular blockade monitoring showed a normal response to vecuronium in the patient. This finding suggests that sensitivities to neuromuscular blocking agents in the patients depend not on the titers of the antibody but also on the presence or absence of the preoperative symptoms such as muscle weakness. It is, however, recommended that neuromuscular blocking agents should be administered carefully under monitoring the neuromuscular function, as is the case for myasthenia gravis, because little is understood about the effect of neuromuscular blocking agent on the neuromuscular function in the asymptomatic patients having anti-AChR antibody.

[General anesthesia with remifentanil for a patient having sinoatrial block and constrictive pulmonary disorder].

There is little report describing the effect of remifentanil on cardiac conduction system. We present a successful anesthetic management with remifentanil in a patient with sick sinus syndrome. A 66-year-old woman (31-kg, 121-cm) having sinoatrial (SA) block was diagnosed as having hepatic cell carcinoma, and radiofrequency ablation (RFA) was scheduled. She was also suffering from kyphosis due to the past history of tuberculous spondylitis. Preoperative examination of her respiratory function indicated a severe constrictive pulmonary disorder. Anesthesia was induced with propofol (30 mg), and maintained with sevoflurane (1-2%) and oxygen/air in combination with remifentanil (0.5 microg x kg(-1) x min(-1)). Temporary pacemaker was prepared during anesthesia. Neither remifentanil nor sevoflurane deteriorated SA block and her heart rate was well controlled. Respiratory dysfunction was not seen in the postoperative course. Our case suggests that remifentanil may be a suitable analgesic for patients with cardiac conduction abnormalities.