Glutamatergic systems in neuropathic pain and emerging non-opioid therapies.

Neuropathic pain, a disease of the somatosensory nervous system, afflicts many individuals and adequate management with current pharmacotherapies remains elusive. The glutamatergic system of neurons, receptors and transporters are intimately involved in pain but, to date, there have been few drugs developed that therapeutically modulate this system. Glutamate transporters, or excitatory amino acid transporters (EAATs), remove excess glutamate around pain transmitting neurons to decrease nociception suggesting that the modulation of glutamate transporters may represent a novel approach to the treatment of pain. This review highlights and summarizes (1) the physiology of the glutamatergic system in neuropathic pain, (2) the preclinical evidence for dysregulation of glutamate transport in animal pain models, and (3) emerging novel therapies that modulate glutamate transporters. Successful drug discovery requires continuous focus on basic and translational methods to fully elucidate the etiologies of this disease to enable the development of targeted therapies. Increasing the efficacy of astrocytic EAATs may serve as a new way to successfully treat those suffering from this devastating disease.

The Utility of BIS™ Monitoring in Anesthesia for Elderly Patients.

Aging leads to anatomic and physiologic changes in the brain, making it more sensitive to the depressant effects of anesthetic medications and increasing the risk of postoperative neurocognitive complications such as postoperative delirium and postoperative cognitive dysfunction. This article explores the implications of anesthesia on elderly patients' brain health, emphasizing the heightened risk of postoperative neurocognitive disorders, and describes the BIS™ Monitoring System as a neuromonitoring tool for anesthesia professionals to assess the depth of anesthesia. The integration of the BIS Monitoring System into clinical practice can contribute to a more tailored and patient-centered approach to anesthesia management, ultimately improving perioperative outcomes and safety.

Time to Post-Anesthesia Neurological Evaluation and Hemodynamic Stability in Carotid Endarterectomy Comparing Three General Anesthetic Techniques Targeted to a Preset Bispectral Index Value: A Pilot Study.

Carotid endarterectomy (CEA) has a 1-5% risk of periprocedural stroke. The ability to emerge patients from anesthesia quickly to detect neurological abnormalities immediately after surgery is vital in this patient population. The objective of this pilot study was to assess if any of three general anesthetic techniques for CEA are associated with a shorter time to a reliable postoperative neurological exam. Secondary objectives were to assess postoperative cognitive dysfunction (POCD), postoperative delirium (POD), and hemodynamic stability. Twenty-one patients undergoing CEA were enrolled and randomized to different combinations of inhalational and intravenous anesthesia: Group A: propofol, remifentanil, and desflurane; Group B: dexmedetomidine, remifentanil, and desflurane; Group C: remifentanil and desflurane. Anesthetic depth was titrated using a bispectral index (BIS) monitor to a goal of 50-60. Time was recorded from surgery end to first meaningful neurological exam. Neurocognitive testing was completed preoperatively and up to 1 week postoperatively to assess POD (3D-CAM) and POCD (Short Blessed Test). Time to first reliable neurological exam was 2 minutes longer in group A (9 min ± 4 min) compared to group B and group C (7 min ± 3 min; 7 min ± 4 min), although this was not statistically significant. In addition, extubation time was significantly longer in group A (11 min) compared to group B and group C (5 min; 6 min) (P = 0.03). 3D -CAM and Short Blessed Test data along with hemodynamics did not differ significantly between the groups. Time to first useful neurologic exam and hemodynamics did not differ between the groups. However, extubation time was significantly prolonged in patients who received propofol, but not dexmedetomidine, as part of their anesthetic for CEA. These findings are best verified in an adequately powered prospective randomized study.