Abstract
Ketamine is a non-competitive N-Methyl-D-Aspartate (NMDA) receptor antagonist whose effect in subanesthetic doses has been studied for chronic pain and mood disorders treatment. It has been proposed that ketamine could change the perception of nociceptive stimuli by modulating the cortical connectivity and altering the top-down mechanisms that control conscious pain perception. As this is a strictly central effect, it would be relevant to provide fresh insight into ketamine's effect on cortical response to external stimuli. Event-related potentials (ERPs) reflect the combined synchronic activity of postsynaptic potentials of many cortical pyramidal neurons similarly oriented, being a well-established technique to study cortical responses to sensory input. Therefore, the aim of this study was to examine the current evidence of subanesthetic ketamine doses on patterns of cortical activity based on ERPs in healthy subjects. To answer the question whether ERPs could be potential markers of the cortical effects of ketamine, we conducted a systematic review of ketamine's effect on ERPs after single and repeated doses. We have searched PubMed, EMBASE and Cochrane Databases and pre-selected 141 articles, 18 of which met the inclusion criteria. Our findings suggest that after ketamine administration some ERP parameters are reduced (reduced N2, P2, and P3 amplitudes, PN and MMN) while others remain stable or are even increased (P50 reduction, PPI, P1, and N1 amplitudes). The current understanding of these effects is that ketamine alters the perceived contrast between distinct visual and auditory stimuli. The analgesic effect of ketamine might also be influenced by a decreased affective discrimination of sensorial information, a finding from studies using ketamine as a model for schizophrenia, but that can give an important hint not only for the treatment of mood disorders, but also to treat pain and ketamine abuse.
Highlights
Ketamine is an antagonist of the N-methyl-D-aspartate (NMDA) receptor
Considering the recent meta-analysis regarding the effects of ketamine on mismatch negativity (MMN), three papers that exclusively studied MMN were not reviewed in detail here (Roser et al, 2011; Schmidt et al, 2012; Hamilton et al, 2018)
We discussed the effects of ketamine on different Event-related potentials (ERPs) components mostly reflecting pre-attentive and attentional processes
Summary
Ketamine is an antagonist of the N-methyl-D-aspartate (NMDA) receptor. It was first synthesized in 1962 and approved by the FDA as an induction agent of general anesthesia in 1970 (Domino, 2010). Ketamine is a dissociative anesthetic with hallucinogenic potential. Effects of Ketamine on ERPs therapy to treat both postoperative acute and chronic pain (Noppers et al, 2010; Michelet et al, 2017). Ketamine has been used to mimic symptoms of schizophrenia in mechanistic studies with healthy subjects (Jeon and Polich, 2003) and in the treatment of refractory major depression (Mathew et al, 2012). The misuse of ketamine as a recreational drug has remarkably increased over the last decade (Degenhardt et al, 2005; Kalsi et al, 2011)
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