Inhibition of spinal ferroptosis-like cell death alleviates hyperalgesia and spontaneous pain in a mouse model of bone cancer pain.

Bone cancer pain (BCP) impairs patients' quality of life. However, the underlying mechanisms are still unclear. This study investigated the role of spinal interneuron death using a pharmacological inhibitor of ferroptosis in a mouse model of BCP. Lewis lung carcinoma cells were inoculated into the femur, resulting in hyperalgesia and spontaneous pain. Biochemical analysis revealed that spinal levels of reactive oxygen species and malondialdehyde were increased, while those of superoxide dismutase were decreased. Histological analysis showed the loss of spinal GAD65+ interneurons and provided ultrastructural evidence of mitochondrial shrinkage. Pharmacologic inhibition of ferroptosis using ferrostatin-1 (FER-1, 10 mg/kg, intraperitoneal for 20 consecutive days) attenuated ferroptosis-associated iron accumulation and lipid peroxidation and alleviated BCP. Furthermore, FER-1 inhibited the pain-associated activation of ERK1/2 and COX-2 expression and prevented the loss of GABAergic interneurons. Moreover, FER-1 improved analgesia by the COX-2 inhibitor Parecoxib. Taken together, this study shows that pharmacological inhibition of ferroptosis-like cell death of spinal interneurons alleviates BCP in mice. The results suggest that ferroptosis is a potential therapeutic target in patients suffering on BCP and possibly other types of pain.

Esketamine versus Sufentanil Applied Prior to Placement of Suspension Laryngoscope.

OBJECTIVE: In laryngeal microsurgery, the insertion of the suspension laryngoscope is a strong stimulus that may cause hemodynamic fluctuations and adverse cardiovascular events. The purpose of this study was to compare the effect of preemptive treatment with esketamine and sufentanil on maintaining hemodynamics and reducing the occurrence of adverse cardiovascular events during the insertion of suspension laryngoscope. METHODS: In this double-blind randomized controlled trial, patients undergoing general anesthesia for laryngeal microsurgery were randomly assigned (1:1) to esketamine 0.5 mg kg-1 (esketamine group) and sufentanyl 0.125 µg kg-1 (sufentanil group) before inserting the laryngoscope, respectively. RESULTS: During the insertion of suspension laryngoscope, the incidence of bradycardia (HR < 60 beats/min) was 39.3% (22/56) in esketamine group, lower than 60.0% (33/55) in sufentanil group (odds ratio [OR], 2.32 [95% CI, 1.11-5.08]; p = 0.029). The incidence of hypotension (MAP <65 mmHg) was 33.9% (19/56) in esketamine group, lower than 56.4% (31/55) in sufentanil group (odds ratio [OR], 2.52 [95% CI, 1.91-5.27]; p = 0.018). The frequency of hypotension in esketamine group was lower than that in sufentanil group (0.36 ± 0.52 vs. 0.56 ± 0.50, p = 0.035). The time-weighted average of HR dropping above 30% of baseline was smaller in esketamine group than in sufentanil group (0.52 ± 2.06 vs. 1.08 ± 2.77, p = 0.006). CONCLUSIONS: These findings showed that compared with preemptive treatment of sufentanil (0.125 µg kg-1 ), esketamine (0.5 mg kg-1 ) was effective in reducing the incidence of cardiovascular adverse events, including bradycardia and hypotension induced by the insertion of suspension laryngoscope during the laryngeal microsurgery. LEVEL OF EVIDENCE: 2 Laryngoscope, 133:3021-3027, 2023.

Effect of Intravenous Ketamine on Hypocranial Pressure Symptoms in Patients with Spinal Anesthetic Cesarean Sections: A Systematic Review and Meta-Analysis.

BACKGROUND: Pregnant women are more likely to suffer post-puncture symptoms such as headaches and nausea due to the outflow of cerebrospinal fluid after spinal anesthesia. Because ketamine has the effect of raising intracranial pressure, it may be able to improve the symptoms of perioperative hypocranial pressure and effectively prevent the occurrence of hypocranial pressure-related side effects. METHOD: Keywords such as ketamine, cesarean section, and spinal anesthesia were searched in databases including Medline, Embase, Web of Science, and Cochrane from 1976 to 2021. Thirteen randomized controlled trials were selected for the meta-analysis. RESULTS: A total of 12 randomized trials involving 2099 participants fulfilled the inclusion criteria. There was no significant association between ketamine and the risk of headaches compared to the placebo (RR = 1.12; 95% CI: 0.53, 2.35; p = 0.77; I² = 62%). There was no significant association between ketamine and nausea compared to the placebo (RR = 0.66; 95% CI: 0.40, 1.09; p = 0.10; I² = 57%). No significant associations between ketamine or the placebo and vomiting were found (RR = 0.94; 95% CI: 0.53, 1.67; p = 0.83; I² = 72%). CONCLUSION: Intravenous ketamine does not improve the symptoms caused by low intracranial pressure after spinal anesthesia in patients undergoing cesarean section.