Opioid usage for pain therapy is limited by its undesirable clinical effects, including paradoxical hyperalgesia, also known as opioid-induced hyperalgesia (OIH). However, the mechanisms associated with the development and maintenance of OIH remain unclear. Here, we investigated the effect of serotonin inhibition by the 5-HT 3 receptor antagonist, ondansetron (OND), as well as serotonin deprivation via its synthesis inhibitor para-chlorophenylalanine, on mouse OIH models, with particular focus on astrocyte activation. Co-administering of OND and morphine, in combination with serotonin depletion, inhibited mechanical hyperalgesia and astrocyte activation in the spinal dorsal horn of mouse OIH models. Although previous studies have suggested that activation of astrocytes in the spinal dorsal horn is essential for the development and maintenance of OIH, herein, treatment with carbenoxolone (CBX), a gap junction inhibitor that suppresses astrocyte activation, did not ameliorate mechanical hyperalgesia in mouse OIH models. These results indicate that serotonin in the spinal dorsal horn, and activation of the 5-HT 3 receptor play essential roles in OIH induced by chronic morphine, while astrocyte activation in the spinal dorsal horn serves as a secondary effect of OIH. Our findings further suggest that serotonergic regulation in the spinal dorsal horn may be a therapeutic target of OIH. Perspective: The current study revealed that the descending serotonergic pain-facilitatory system in the spinal dorsal horn is crucial in OIH, and that activation of astrocytes is a secondary phenotype of OIH. Our study offers new therapeutic targets for OIH and may help reduce inappropriate opioid use.
We report the anesthetic management of a patient scheduled for tumor resection with a giant ovarian tumor containing 83 l of fluid. A 59-year-old woman [height 154 cm; weight 146 kg (ideal: 52 kg)] with a giant ovarian tumor was scheduled for tumor resection. Her preoperative abdominal circumference was 194 cm, which made supine positioning difficult. The thoracoabdominal computed tomography revealed a right giant cystic ovarian tumor with an estimated mass of 100 kg. Evidence of malignant tumor was not observed. In the operation room, she was intubated using a video laryngoscope (Airway Scope®, Hoya, Tokyo, Japan) in a semirecumbent position under conscious sedation. Following general anesthesia, the tumor fluid was gradually aspirated at a rate of 500 ml/min, and during this procedure, spontaneous respiration was preserved with pressure support ventilation. After the fluid was drained, the tumor was resected in a supine position. There were no major perioperative complications in hemodynamic and respiratory status, such as supine hypotensive syndrome or re-expansion pulmonary edema. Her weight decreased to 50 kg postoperatively. Maintenance of spontaneous respiration and slow aspiration of the tumor fluid prevented respiratory and hemodynamic failure and resulted in safe anesthesia management during giant ovarian tumor resection.
We retrospectively reviewed outcomes of video-assisted thoracoscopic surgery of the esophagus (VATS-E) in the left lateral position (group L, n=70) and in the prone position (group P, n=70) in our hospital. The maximum arterial carbon dioxide tension was higher and a marked reduction in percutaneous arterial oxygen saturation was more common in group P. Moreover, the induction time of anesthesia was longer in group P, in which it was more difficult to change postural position. However, the amount of bleeding, total infusion volume, intraoperative water balance, the incidence of arrhythmia, and poor surgical field visibility during thoracic manipulation were significantly lower in group P than in group L. Thus, VATS-E in the prone position provided stable hemodynamics and safe management of patients, although there remain issues to be resolved, including respiratory care and changes in postural position.
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