RESUMEN
BACKGROUND: Yokukansan, a traditional Japanese medicine (Kampo), has been widely used to treat neurosis, dementia, and chronic pain. Previous in vitro studies have suggested that Yokukansan acts as a partial agonist of the 5-HT1A receptor, resulting in amelioration of chronic pain through inhibition of nociceptive neuronal activity. However, its effectiveness for treating postoperative pain remains unknown, although its analgesic mechanism of action has been suggested to involve serotonin and glutamatergic neurotransmission. This study aimed to investigate the effect of Yokukansan on postoperative pain in an animal model. METHODS: A mouse model of postoperative pain was created by plantar incision, and Yokukansan was administered orally the day after paw incision. Pain thresholds for mechanical and heat stimuli were examined in a behavioral experiment. In addition, to clarify the involvement of the serotonergic nervous system, we examined the analgesic effects of Yokukansan in mice that were serotonin-depleted by para-chlorophenylalanine (PCPA) treatment and intrathecal administration of NAN-190, 5-HT1A receptor antagonist. RESULTS: Orally administered Yokukansan increased the pain threshold dose-dependent in postoperative pain model mice. Pretreatment of para-chlorophenylalanine dramatically suppressed serotonin immunoreactivity in the spinal dorsal horn without changing the pain threshold after the paw incision. The analgesic effect of Yokukansan tended to be attenuated by para-chlorophenylalanine pretreatment and significantly attenuated by intrathecal administration of 2.5 µg of NAN-190 compared to that in postoperative pain model mice without para-chlorophenylalanine treatment and NAN-190 administration. CONCLUSION: This study demonstrated that oral administration of Yokukansan has acute analgesic effects in postoperative pain model mice. Behavioral experiments using serotonin-depleted mice and mice intrathecally administered with a 5-HT1A receptor antagonist suggested that Yokukansan acts as an agonist at the 5-HT1A receptor, one of the serotonin receptors, to produce analgesia.
Asunto(s)
Analgésicos , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Dolor Postoperatorio , Animales , Ratones , Medicamentos Herbarios Chinos/farmacología , Masculino , Dolor Postoperatorio/tratamiento farmacológico , Analgésicos/farmacología , Serotonina/metabolismo , Receptor de Serotonina 5-HT1A/metabolismo , Receptor de Serotonina 5-HT1A/efectos de los fármacos , Administración Oral , Ratones Endogámicos ICRRESUMEN
BACKGROUND: Some anesthetic drugs reduce the amplitude of transcranial electrical motor-evoked potentials (MEPs). Remimazolam, a new benzodiazepine, has been suggested to have little effect on MEP amplitude. This prospective, preliminary, dose-escalation study aimed to assess whether remimazolam is associated with lower MEP amplitude in a dose-dependent manner. METHODS: Ten adult patients scheduled for posterior spinal fusion were included in this study. General anesthesia was induced with a continuous infusion of remifentanil and remimazolam. After the patient lost consciousness, the infusion rate of remimazolam was set to 1 mg/kg/h, and the patient underwent tracheal intubation. Baseline MEPs were recorded under 1 mg/kg/h of remimazolam in a prone position. Thereafter, the infusion rate of remimazolam was increased to 2 mg/kg/h, with a bolus of 0.1 mg/kg. Ten minutes after the increment, the evoked potentials were then recorded again. The primary endpoint was the MEP amplitude recorded in the left gastrocnemius muscle at 2 time points. RESULTS: There was no difference in MEP amplitude recorded from the left gastrocnemius muscle before and after increasing remimazolam (median [interquartile range]: 0.93 [0.65 to 1.25] mV and 0.70 [0.43 to 1.26] mV, respectively; P=0.08). The average time from the cessation of remimazolam administration to neurological examination after surgery was 4 minutes using flumazenil. CONCLUSIONS: This preliminary study suggests that increasing remimazolam from 1 to 2 mg/kg/h might have an insignificant effect on transcranial electric MEPs.
RESUMEN
BACKGROUND: Dexamethasone is used perioperatively as an antiemetic for postoperative nausea and vomiting. Evidence and mechanism linking dexamethasone and hypertensive attack of pheochromocytoma during anesthesia have not been reported. CASE DESCRIPTION: We report a case of a hypertensive attack during anesthetic induction immediately after dexamethasone administration in a 35-year-old woman with adrenal pheochromocytoma. Approximately 2 min after the anesthetic drugs and dexamethasone were administered, her arterial blood pressure suddenly increased from 143/79 to 243/116 mmHg during manual mask ventilation. Since tracheal intubation had not been performed yet, dexamethasone could be a causative agent of hypertensive episodes. The surgery and anesthesia were uneventful. She was admitted to the intensive care unit to have her blood pressure controlled subsequently. CONCLUSIONS: Dexamethasone should be used with caution in patients with adrenal pheochromocytoma on account of the risk of hypertensive attacks.