Anesthesiology
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Randomized Controlled Trial
A Phase 1, Dose-escalation, Double-blind, Block-randomized, Controlled Trial of Safety and Efficacy of Neosaxitoxin Alone and in Combination with 0.2% Bupivacaine, with and without Epinephrine, for Cutaneous Anesthesia.
Neosaxitoxin (NeoSTX) is a site-1 sodium channel blocker that produces prolonged local anesthesia in animals and humans. Under a Food and Drug Administration-approved phase 1 Investigational New Drug trial, the authors evaluated safety and efficacy of NeoSTX alone and combined with 0.2% bupivacaine (Bup) with and without epinephrine. ⋯ NeoSTX combinations have a tolerable side effect profile and appear promising for prolonged local anesthesia.
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Isoflurane induces cell death in neurons undergoing synaptogenesis via increased production of pro-brain-derived neurotrophic factor (proBDNF) and activation of postsynaptic p75 neurotrophin receptor (p75). Astrocytes express p75, but their role in neuronal p75-mediated cell death remains unclear. The authors investigated whether astrocytes have the capacity to buffer increases in proBDNF and protect against isoflurane/p75 neurotoxicity. ⋯ The presence of astrocytes provides protection to growing neurons by buffering increased levels of proBDNF induced by isoflurane. These findings may hold clinical significance for the neonatal and injured brain where increased levels of proBDNF impair neurogenesis.
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Patients with neuropathic pain show reduced endogenous analgesia induced by a conditioned noxious stimulus. Here, the authors tested whether peripheral nerve injury impairs descending noradrenergic inhibition from the locus coeruleus (LC) after L5-L6 spinal nerve ligation (SNL) in rats. ⋯ These results suggest that increased extracellular glutamate in the LC consequent to down-regulation of GLT-1 contributes to LC dysfunction and impaired pain-evoked endogenous analgesia after nerve injury.
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Editorial Comment
Epigenetics: The Epicenter for Future Anesthesia Research?