A novel approach to pharmaco‐EEG for investigating analgesics: assessment of spectral indices in single‐sweep evoked brain potentials

• Published in: British journal of clinical pharmacology Vol. 76; no. 6; pp. 951 - 963
• Main Authors: Gram, Mikkel, Graversen, Carina, Nielsen, Anders K., Arendt‐Nielsen, Thomas, Mørch, Carsten D., Andresen, Trine, Drewes, Asbjørn M.
• Format: Journal Article
• Language: English
• Published: England Blackwell Science Inc 01.12.2013
• Subjects: Adult; analgesic; Analgesics, Opioid - administration & dosage; Analgesics, Opioid - pharmacology; Analgesics, Opioid - therapeutic use; Brain - drug effects; Brain - physiopathology; Buprenorphine - administration & dosage; Buprenorphine - pharmacology; Buprenorphine - therapeutic use; Cross-Over Studies; Data Interpretation, Statistical; Double-Blind Method; Electric Stimulation; electroencephalographic; Electroencephalography - drug effects; evoked potentials; Evoked Potentials - drug effects; Evoked Potentials - physiology; Fentanyl - administration & dosage; Fentanyl - pharmacology; Fentanyl - therapeutic use; Healthy Volunteers; Humans; Male; Methods in Clinical Pharmacology; opioids; Pain - drug therapy; Pain - physiopathology; Pain Measurement; pharmaco‐EEG; single‐sweep; Transdermal Patch; Young Adult; electroencephalographic; analgesic; EP; single-sweep; evoked potentials; opioids; pharmaco-EEG
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1111/bcp.12120

Aims To compare results from analysis of averaged and single‐sweep evoked brain potentials (EPs) by visual inspection and spectral analysis in order to identify an objective measure for the analgesic effect of buprenorphine and fentanyl. Methods Twenty‐two healthy males were included in a randomized study to assess the changes in EPs after 110 sweeps of painful electrical stimulation to the median nerve following treatment with buprenorphine, fentanyl or placebo patches. Bone pressure, cutaneous heat and electrical pain ratings were assessed. EPs and pain assessments were obtained before drug administration, 24, 48, 72 and 144 h after beginning of treatment. Features from EPs were extracted by three different approaches: (i) visual inspection of amplitude and latency of the main peaks in the average EPs, (ii) spectral distribution of the average EPs and (iii) spectral distribution of the EPs from single‐sweeps. Results Visual inspection revealed no difference between active treatments and placebo (all P > 0.05). Spectral distribution of the averaged potentials showed a decrease in the beta (12–32 Hz) band for fentanyl (P = 0.036), which however did not correlate with pain ratings. Spectral distribution in the single‐sweep EPs revealed significant increases in the theta, alpha and beta bands for buprenorphine (all P < 0.05) as well as theta band increase for fentanyl (P = 0.05). For buprenorphine, beta band activity correlated with bone pressure and cutaneous heat pain (both P = 0.04, r = 0.90). Conclusion In conclusion single‐sweep spectral band analysis increases the information on the response of the brain to opioids and may be used to identify the response to analgesics.