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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.

Background: Nasogastric tubes can be easily inserted in patients under general anesthesia. However, for difficult cases, insertion techniques that can be used in routine clinical practice are limited. SUZY forceps are designed for the removal of pharyngolaryngeal foreign bodies under guidance of a McGrath videolaryngoscope. We hypothesized that using SUZY forceps under McGrath videolaryngoscopic guidance may facilitate nasogastric tube insertion and tested this in a randomized controlled trial. Methods: Adult patients who underwent gastrointestinal or hepato-pancreato-biliary surgery were randomly allocated to 2 groups; the SUZY group and the Magill group. Patients, nurses, and all clinical staff except for the attending anesthesiologist were blinded to group assignment throughout the study. After anesthesia induction, insertion of the nasogastric tube was performed by skilled anesthesiologists with either SUZY or Magill forceps according to group allocation under McGrath videolaryngoscopic guidance. The primary endpoint was insertion time which was defined as the time required to advance the nasogastric tube by 55 cm from the nostril. Secondary endpoints were the success rates of the nasogastric tube insertion, which were defined as a 55-cm advancement from the nostril at the 1st, 2nd, and 3rd attempt, proper insertion rate, the severity of pharyngolaryngeal complications, and hemodynamic parameters during nasogastric tube insertion. Results: Sixty patients were randomized and none of these patients were excluded from the final analysis. The median [interquartile range] insertion time was 25 [18–33] seconds in the SUZY group, and 33 [21–54] seconds in the Magill group ( P = .02). Success rates were not different between the groups (97% and 80% in the SUZY and Magill group at 1st attempt, respectively, P = .10). Both, the severity score of the mucosal injury and the severity of sore throat were higher in the Magill than in the SUZY group, whereas the degree of hoarseness did not differ between the 2 groups. Hemodynamic parameters were not significantly different between the groups. Conclusion: Using SUZY forceps under McGrath videolaryngoscopic guidance reduced the time required to insert a nasogastric tube and the severity of pharyngolaryngeal complications, when compared to using Magill forceps.

Antireflection (AR) layer coated semiconductor laser diodes may have many applications, particularly as external cavity diodes for optical memory heads. The electron cyclotron resonance (ECR) sputtering system was used for preparing AR coatings which consist of both SiO2 and Si3N4 phases. The refractive index and the thickness of the AR coatings were adjusted by controlling numerous deposition parameters, including the relative flow ratio of O2 and N2 gas flow, the total gas flow rate, the RF and ECR power, and the deposition time. AR coated AlGaAs laser diodes do not show a sharp threshold in the light output-current characteristic curve and have good potential for application in the lensless optical floppy systems.

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