Electroencephalography and analgesics

Abstract

To assess centrally mediated analgesic mechanisms in clinical trials with pain patients, objective standardized methods such as electroencephalography (EEG) has many advantages. The aim of this review is to provide the reader with an overview of present findings in analgesics assessed with spontaneous EEG and evoked brain potentials (EPs) in humans. Furthermore, EEG methodologies will be discussed with respect to translation from animals to humans and future perspectives in predicting analgesic efficacy. We searched PubMed with MeSH terms 'analgesics', 'electroencephalography' and 'evoked potentials' for relevant articles. Combined with a search in their reference lists 15 articles on spontaneous EEG and 55 papers on EPs were identified. Overall, opioids produced increased activity in the delta band in the spontaneous EEG, but increases in higher frequency bands were also seen. The EP amplitudes decreased in the majority of studies. Anticonvulsants used as analgesics showed inconsistent results. The N-methyl-D-aspartate receptor antagonist ketamine showed an increase in the theta band in spontaneous EEG and decreases in EP amplitudes. Tricyclic antidepressants increased the activity in the delta, theta and beta bands in the spontaneous EEG while EPs were inconsistently affected. Weak analgesics were mainly investigated with EPs and a decrease in amplitudes was generally observed. This review reveals that both spontaneous EEG and EPs are widely used as biomarkers for analgesic drug effects. Methodological differences are common and a more uniform approach will further enhance the value of such biomarkers for drug development and prediction of treatment response in individual patients.

Keywords: analgesics; electroencephalography; evoked potentials; pain; pharmacologic actions.

Figure 1

Spontaneous EEG representing the overall cortical neural processing is a mix of several brain oscillations. (A) Oscillations can be presented in a time domain. (B) The frequency distribution can be presented in a time–frequency domain. (C) Traditionally the oscillations are decomposed into specific frequency bands, with the slowest oscillations in the delta band (1.5–6 Hz) and the fastest oscillations into the beta band (12.5–30 Hz). Thus the frequency distribution can be presented in the frequency domain as the relative contributions of each frequency band to the overall power of the EEG

Figure 2

Interactions among brain regions hypothesized to constitute the homeostatic system that generates and regulates the electroencephalographic power spectrum

Figure 3

Evoked brain potential during painful electrical stimulation at the median nerve. The potential is an average of several repeated and identical stimulations. The cortical processing of the painful stimuli is traditionally assessed as amplitude and latency characteristics of both negative and positive peaks