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S-Ketamine's Effect Changes the Cortical Electrophysiological Activity Related to Semantic Affective Dimension of Pain: A Placebo- Controlled Study in Healthy Male Individuals.
Front Neurosci 2019; 13:959FN

Abstract

Background

Previous studies using the electroencephalogram (EEG) technique pointed out that ketamine decreases the amplitude of cortical electrophysiological signal during cognitive tasks, although its effects on the perception and emotional-valence judgment of stimuli are still unknown.

Objective

We evaluated the effect of S-ketamine on affective dimension of pain using EEG and behavioral measures. The hypothesis was that S-ketamine would be more effective than placebo, both within and between groups, to attenuate the EEG signal elicited by target and non-target words.

Methods

This double-blind parallel placebo-controlled study enrolled 24 healthy male volunteers between 19 and 40 years old. They were randomized to receive intravenous S-ketamine (n = 12) at a plasmatic concentration of 60 ng/ml or placebo (n = 12). Participants completed a computerized oddball paradigm containing written words semantically related to pain (targets), and non-pain related words (standard). The volunteers had to classify the words either as "positive," "negative" or "neutral" (emotional valence judgment). The paradigm consisted in 6 blocks of 50 words each with a fixed 4:1 target/non-target rate presented in a single run. Infusion started during the interval between the 3rd and 4th blocks, for both groups. EEG signal was registered using four channels (Fz, Pz, Pz, and Oz, according to the 10-20 EEG system) with a linked-earlobe reference. The area under the curve (AUC) of the N200 (interval of 100-200 ms) and P300 (300-500 ms) components of event-related potentials (ERPs) was measured for each channel.

Results

S-ketamine produced substantial difference (delta) in the AUC of grand average ERP components N200 (P = 0.05) and P300 (P = 0.02) at Pz during infusion period when compared to placebo infusion for both targets and non-targets. S-ketamine was also associated with a decrease in the amount of pain-related words judged as negative from before to after infusion [mean = 0.83 (SD = 0.09) vs. mean = 0.73 (SD = 0.11), respectively; P = 0.04].

Conclusion

Our findings suggest that S-ketamine actively changed the semantic processing of written words. There was an increase in electrophysiological response for pain-related stimuli and a decrease for standard stimuli, as evidenced by the increased delta of AUCs. Behaviorally, S-ketamine seems to have produced an emotional and discrimination blunting effect for pain-related words.

Clinical Trial Registration

www.ClinicalTrials.gov, identifier NCT03915938.

Authors+Show Affiliations

Post-graduation Program in Medicine: Medical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. Laboratory of Pain and Neuromodulation, Clinical Hospital of Porto Alegre, Porto Alegre, Brazil.Post-graduation Program in Medicine: Medical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. Laboratory of Pain and Neuromodulation, Clinical Hospital of Porto Alegre, Porto Alegre, Brazil.Post-graduation Program in Medicine: Medical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. Laboratory of Pain and Neuromodulation, Clinical Hospital of Porto Alegre, Porto Alegre, Brazil.Post-graduation Program in Medicine: Medical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. Laboratory of Pain and Neuromodulation, Clinical Hospital of Porto Alegre, Porto Alegre, Brazil.Post-graduation Program in Medicine: Medical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. Laboratory of Pain and Neuromodulation, Clinical Hospital of Porto Alegre, Porto Alegre, Brazil.Clinical Research Center, Clinical Hospital of Porto Alegre, Porto Alegre, Brazil.Post-graduation Program in Biological Sciences: Physiology, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. Pharmacology of Pain and Neuromodulation: Pre-clinical Investigations, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA, United States.Post-graduation Program in Psychology, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.Post-graduation Program in Medicine: Medical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. Laboratory of Pain and Neuromodulation, Clinical Hospital of Porto Alegre, Porto Alegre, Brazil.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31611759

Citation

Schwertner, André, et al. "S-Ketamine's Effect Changes the Cortical Electrophysiological Activity Related to Semantic Affective Dimension of Pain: a Placebo- Controlled Study in Healthy Male Individuals." Frontiers in Neuroscience, vol. 13, 2019, p. 959.
Schwertner A, Zortea M, Torres FV, et al. S-Ketamine's Effect Changes the Cortical Electrophysiological Activity Related to Semantic Affective Dimension of Pain: A Placebo- Controlled Study in Healthy Male Individuals. Front Neurosci. 2019;13:959.
Schwertner, A., Zortea, M., Torres, F. V., Ramalho, L., Alves, C. F. D. S., Lannig, G., ... Caumo, W. (2019). S-Ketamine's Effect Changes the Cortical Electrophysiological Activity Related to Semantic Affective Dimension of Pain: A Placebo- Controlled Study in Healthy Male Individuals. Frontiers in Neuroscience, 13, p. 959. doi:10.3389/fnins.2019.00959.
Schwertner A, et al. S-Ketamine's Effect Changes the Cortical Electrophysiological Activity Related to Semantic Affective Dimension of Pain: a Placebo- Controlled Study in Healthy Male Individuals. Front Neurosci. 2019;13:959. PubMed PMID: 31611759.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - S-Ketamine's Effect Changes the Cortical Electrophysiological Activity Related to Semantic Affective Dimension of Pain: A Placebo- Controlled Study in Healthy Male Individuals. AU - Schwertner,André, AU - Zortea,Maxciel, AU - Torres,Felipe Vasconcelos, AU - Ramalho,Leticia, AU - Alves,Camila Fernanda da Silveira, AU - Lannig,Guilherme, AU - Torres,Iraci L S, AU - Fregni,Felipe, AU - Gauer,Gustavo, AU - Caumo,Wolnei, Y1 - 2019/09/13/ PY - 2019/05/26/received PY - 2019/08/26/accepted PY - 2019/10/16/entrez PY - 2019/10/16/pubmed PY - 2019/10/16/medline KW - ERPs KW - P300 KW - ketamine KW - oddball KW - pain SP - 959 EP - 959 JF - Frontiers in neuroscience JO - Front Neurosci VL - 13 N2 - Background: Previous studies using the electroencephalogram (EEG) technique pointed out that ketamine decreases the amplitude of cortical electrophysiological signal during cognitive tasks, although its effects on the perception and emotional-valence judgment of stimuli are still unknown. Objective: We evaluated the effect of S-ketamine on affective dimension of pain using EEG and behavioral measures. The hypothesis was that S-ketamine would be more effective than placebo, both within and between groups, to attenuate the EEG signal elicited by target and non-target words. Methods: This double-blind parallel placebo-controlled study enrolled 24 healthy male volunteers between 19 and 40 years old. They were randomized to receive intravenous S-ketamine (n = 12) at a plasmatic concentration of 60 ng/ml or placebo (n = 12). Participants completed a computerized oddball paradigm containing written words semantically related to pain (targets), and non-pain related words (standard). The volunteers had to classify the words either as "positive," "negative" or "neutral" (emotional valence judgment). The paradigm consisted in 6 blocks of 50 words each with a fixed 4:1 target/non-target rate presented in a single run. Infusion started during the interval between the 3rd and 4th blocks, for both groups. EEG signal was registered using four channels (Fz, Pz, Pz, and Oz, according to the 10-20 EEG system) with a linked-earlobe reference. The area under the curve (AUC) of the N200 (interval of 100-200 ms) and P300 (300-500 ms) components of event-related potentials (ERPs) was measured for each channel. Results: S-ketamine produced substantial difference (delta) in the AUC of grand average ERP components N200 (P = 0.05) and P300 (P = 0.02) at Pz during infusion period when compared to placebo infusion for both targets and non-targets. S-ketamine was also associated with a decrease in the amount of pain-related words judged as negative from before to after infusion [mean = 0.83 (SD = 0.09) vs. mean = 0.73 (SD = 0.11), respectively; P = 0.04]. Conclusion: Our findings suggest that S-ketamine actively changed the semantic processing of written words. There was an increase in electrophysiological response for pain-related stimuli and a decrease for standard stimuli, as evidenced by the increased delta of AUCs. Behaviorally, S-ketamine seems to have produced an emotional and discrimination blunting effect for pain-related words. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03915938. SN - 1662-4548 UR - https://www.unboundmedicine.com/medline/citation/31611759/S-Ketamine's_Effect_Changes_the_Cortical_Electrophysiological_Activity_Related_to_Semantic_Affective_Dimension_of_Pain:_A_Placebo-_Controlled_Study_in_Healthy_Male_Individuals L2 - https://doi.org/10.3389/fnins.2019.00959 DB - PRIME DP - Unbound Medicine ER -