Tolerance seriously impedes the application of morphine in clinical medicine. Thus, it is necessary to investigate the exact mechanisms and efficient treatment. Microglial activation and neuroinflammation in the spinal cord are thought to play pivotal roles on the genesis and maintaining of morphine tolerance. Activation of adenosine monophosphate-activated kinase (AMPK) has been associated with the inhibition of inflammatory nociception. Metformin, a biguanide class of antidiabetic drugs and activator of AMPK, has a potential anti-inflammatory effect. The present study evaluated the effects and potential mechanisms of metformin in inhibiting microglial activation and alleviating the antinociceptive tolerance of morphine. The microglial cell line BV-2 cells and mouse brain-derived endothelial cell line bEnd3 cells were used. Cytokine expression was measured using quantitative polymerase chain reaction. Cell signaling was assayed by western blot and immunohistochemistry. The antinociception and morphine tolerance were assessed in CD-1 mice using tail-flick tests. We found that morphine-activated BV-2 cells, including the upregulation of p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation, pro-inflammatory cytokines, and Toll-like receptor-4 (TLR-4) mRNA expression, which was inhibited by metformin. Metformin suppressed morphine-induced BV-2 cells activation through increasing AMPK phosphorylation, which was reversed by the AMPK inhibitor compound C. Additionally, in BV-2 cells, morphine did not affect the cell viability and the mRNA expression of anti-inflammatory cytokines. In bEnd3 cells, morphine did not affect the mRNA expression of interleukin-1β (IL-1β), but increased IL-6 and tumor necrosis factor-α (TNF-α) mRNA expression; the effect was inhibited by metformin. Morphine also did not affect the mRNA expression of TLR-4 and chemokine ligand 2 (CCL2). Furthermore, systemic administration of metformin significantly blocked morphine-induced microglial activation in the spinal cord and then attenuated the development of chronic morphine tolerance in mice. Metformin significantly attenuated morphine antinociceptive tolerance by suppressing morphine-induced microglial activation through increasing AMPK phosphorylation.

The lumbar sympathetic nerve block stands as a pivotal approach in managing complex regional pain syndrome (CRPS) in the lower limbs. Retroperitoneal hemorrhage is an extremely rare and severe complication of lumbar sympathetic nerve block. Here, we report for the first time a case of retroperitoneal hemorrhage that initially presented with symptoms of femoral nerve compression. An 81-year-old elderly female was diagnosed with CRPS. After undergoing an ultrasound-guided lumbar sympathetic nerve block at our hospital, discomfort in her right lower back was experienced, followed by stabbing pain, numbness in the anterior thigh, and significant lower limb movement impairment. We considered that the femoral nerve might be compressed by a hematoma or abscess. An emergency percutaneous drainage was performed, resulting in partial symptom relief. However, two days later, signs of hemorrhagic shock were observed in the patient. An emergency lumbar arterial embolization was performed, effectively stabilizing her vital signs. One week later, lower limb pain and numbness disappeared, and right lower limb motor function fully recovered. When retroperitoneal hemorrhage is suspected, prompt computed tomography (CT) or bedside ultrasound should be conducted. Once imaging supports the diagnosis, immediate digital subtraction angiography (DSA) could be utilized to identify the bleeding source and conduct embolization.

Background: Emergence agitation after general anesthesia may cause several undesirable events in the clinic during patient anesthesia recovery, and acute alcohol intoxication, while rare in surgery, is one of the risk factors. Case presentation: A 66-year-old male patient was found to have pancreatic tail neoplasm upon computed tomography (CT) examination. The surgeon planned to resect the pancreatic tail under general anesthesia. However, the surgeon found extensive tumor metastasis in the abdominal cavity, and thus performed a neurolytic celiac plexus block (NCPB) with 40 ml 95% ethyl alcohol and finished the surgery in approximately 1 h. Twenty minutes later, the patient was extubated and developed significant emergence agitation in the postoperative care unit, characterized by restlessness, uncontrollable movements, confusion and disorientation. The patient was flushed and febrile with an alcohol smell in his breath and was unable to follow commands. Patient symptoms were suspected to be due to acute alcohol intoxication. Thus, the patient was given 40 mg of propofol intravenously. Following treatment, the patient recovered with less confusion and disorientation after approximately 10 min. After treatment with propofol twice more, he regained consciousness, was calm and cooperative, had no pain, and could obey instructions approximately 1 h and 40 min following the last treatment. Following this treatment, the patient was transferred to the inpatient ward and felt well. Conclusions: It is paramount to correctly identify the underlying cause of emergence agitation in order to successfully manage patient symptoms, since treatment plans vary between different etiological causes. Emergence agitation may be due to acute alcohol intoxication after intraoperative use of alcohol.

Rationale: Parkinson disease (PD) is a chronic neurodegenerative condition often suffered by the elderly. Upper airway obstruction, though rare in patients with PD, can be life threatening and is associated with vocal cord paralysis, laryngeal spasm, and dystonia of jaw and neck muscles. Patient concerns: We describe a life-threatening upper airway obstruction caused by bilateral vocal cord paralysis, in an elderly man with PD, during extubation after general anesthesia. Diagnoses: Based on clinical presentation and visual laryngoscopy, the patient was diagnosed with laryngeal spasm and bilateral vocal cord paralysis after extubation. Interventions: Re-intubation was carried out and dopamine hydrazine tablets were administered via a nasal feeding tube. Outcomes: After re-intubation and further treatment, the endotracheal tube was successfully removed and no symptoms of respiratory distress were observed. Lessons: Patients with PD may be at a risk of life-threatening upper airway obstruction after extubation, which should be prevented systematically.