Insulin resistance alters cortical inhibitory neurons and microglia to exacerbate Alzheimer's knock-in mouse phenotypes.

Pain is an unpleasant sensory or emotional sensation resulting from the complex interaction of neuro‐inflammatory activity and complex peripheral and central nervous information‐processing networks []. Variability in pain perception and response to analgesic medication is related to factors such as age, sex, pharmacokinetics, pharmacodynamics, and pharmacogenetic profiles, as well as cognitive, behavioral, cultural, and emotional factors [, ]. Clinical practice needs to be supported by a thorough understanding of the pharmacokinetics of analgesics to ensure safe and effective dosing regimens are used to appropriately manage pain and minimize uncertainties in pharmacokinetic responses, especially in the pediatric population [, ]. Multimodal analgesia aims to provide optimal comfort and minimize distress in the acute perioperative pain setting by utilizing a combination of analgesics that act by different mechanisms, thereby reducing the analgesic requirements of each type of medication and their risk of adverse effects []. Multimodal analgesic combinations may include simple analgesics (acetaminophen and ibuprofen), opioids, local anesthetics, adjuvant analgesics (such as NMDA receptor antagonists, alpha‐2 agonists, and gabapentinoids) with other non‐pharmacological strategies (such as rehabilitation, education, hypnosis, cognitive behavioral therapy, relaxation, imagery, controlled breathing, transcutaneous electrical nerve stimulation, acupuncture, massage, and distraction techniques). A multimodal approach provides significant benefits, including reductions in pain intensity, opioid dose requirements, and opioid‐related adverse events [, ]. Intravenous lidocaine therapy (IVLT) has been used as an adjuvant analgesic agent for multimodal analgesia in both pediatric and adult postoperative pain management [, , , , , ]. Lidocaine is an amide‐type local anesthetic that acts on voltage‐gated ion channels to impede signaling transmission within the peripheral and central nervous system []. Lidocaine has analgesic, anti‐hyperalgesia, and anti‐inflammatory effects and may reduce pain and postoperative nausea and vomiting []. In adults, lidocaine pharmacokinetics are well characterized. With bolus administration and infusions lasting less than 12 h, lidocaine displays biphasic elimination and linear pharmacokinetics with a terminal half‐life of about 100 min []. Lidocaine is metabolized rapidly in the liver to multiple metabolites: active monoethylglycinexylidide (MEGX), active glycinexylidide (GX), and inactive N‐ethylglycine (NEG). Children older than 6–7 months without hepatic, cardiac, or renal impairment eliminate intravenous lidocaine, similarly to adults, by metabolism and excretion of lidocaine and its metabolites [].