Ketamine's Effect Changes the Cortical Electrophysiological Activity Related to Semantic Affective Dimension of Pain

Ketamine's Effect Changes the Cortical Electrophysiological Activity Related to Semantic Affective Dimension of Pain

Ketamine's Effect Changes the Cortical Electrophysiological Activity Related to Semantic Affective Dimension of Pain: a Placebo-controlled Study in Healthy Male Subjects

This is a clinical trial that intend to determine the effects of S-ketamine on event-related potentials associated with semantic affective pain-processing

Ketamine is a unique anesthetic with neural effects that are distinct from more commonly-used γ-aminobutyric acid agonists. Evidence suggest that analgesic effect of ketamine is primarily related to the affective than the sensorial aspects of pain interpretation. The investigators investigated whether ketamine, a noncompetitive NMDA antagonist, would modify the perceived emotional valence of pain-related words when compared to non-pain-related ones in healthy volunteers. Using a single session double-blind parallel placebo-controlled design, 24 healthy volunteers were randomized to receive intravenous S-ketamine (n=12) or placebo (n=12). During infusion (plasmatic target of 60 ng/ml), the effects of ketamine were recorded using EEG and oddball behavioral data was monitored. Evoked potentials (N200 and P300 components) were recorded during performance of a semantic written word oddball task containing pain-related (targets) and non-pain-related words (standards). Expected results: The findings of this study can help in the understanding of neurophysiologic mechanisms involved in ketamine's effects both in psychiatric diseases as in the treatment of postoperative acute and chronic pain.

S-Ketamine will be diluted in normal saline and administrated in a target controlled infusion using an infusion pump to obtain a plasma target of 60 ng/ml according to Domino's model. Infusion will start during the interval between the 3rd and 4th blocks of the task.

A previously prepared identical solution containing only normal saline will be infused at the same infusion rates of group ketamine.

S-ketamine will be administered in precalculated infusion rates to obtain a plasmatic level of 60 ng/ml

EEG will be recorded during all task time. The main outcome will be the area under de curve (AUC) of the grand averaged mean differences between event-related potencials (ERPs) elicited by target and non-target words at 100-200, 300-500 and 800-900 ms after stimulus presentation for parietal electrophysiological signal (Pz). The ERPs represent the averaged voltage of several trials.

After viewing each word, volunteers were asked to classify them according to the semantic valence in the following categories: "positive," "negative" or "neutral."

Sedation will be rated using an analogue visual scale ranging of 0 (completely awake) to 100 (sleeping).

Inclusion Criteria: male healthy subjects with higher education level Exclusion Criteria: do not understand Portuguese language obese patients (BMI > 27 kg/m2) use of NSAID, steroids, analgesics, anticonvulsant drugs, as well as alpha and beta-blockers score ≥ 13 on Beck II Questionnaire sleep deprivation in the night before evaluation

Schwertner A, Zortea M, Torres FV, Ramalho L, Alves CFDS, Lannig G, Torres ILS, Fregni F, Gauer G, Caumo W. 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 Sep 13;13:959. doi: 10.3389/fnins.2019.00959. eCollection 2019.