The analgesic effect of pregabalin in patients with chronic pain is reflected by changes in pharmaco‐EEG spectral indices

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Pregabalin is an anticonvulsive agent prescribed as a secondary analgesic for patients when standard pain treatment is insufficient. • The analgesic effect resides in the central nervous system. • The central analgesic effect can be evaluated by electroencephalography. WHAT THIS STUDY ADDS • The analgesic effect of pregabalin is reflected as a slowing of brain oscillations. • The slowing of brain oscillations for each individual patient is correlated with subjective pain scores. • The developed methodology may be used as a mechanistic approach to monitor the analgesic effect of pregabalin in pharmacological studies. AIM To identify electroencephalographic (EEG) biomarkers for the analgesic effect of pregabalin in patients with chronic visceral pain. METHODS This was a double‐blind, placebo‐controlled study in 31 patients suffering from visceral pain due to chronic pancreatitis. Patients received increasing doses of pregabalin (75 mg–300 mg twice a day) or matching placebo during 3 weeks of treatment. Pain scores were documented in a diary based on a visual analogue scale. In addition, brief pain inventory‐short form (BPI) and quality of life questionnaires were collected prior to and after the study period. Multi‐channel resting EEG was recorded before treatment onset and at the end of the study. Changes in EEG spectral indices were extracted, and individual changes were classified by a support vector machine (SVM) to discriminate the pregabalin and placebo responses. Changes in individual spectral indices and pain scores were correlated. RESULTS Pregabalin increased normalized intensity in low spectral indices, most prominent in the theta band (3.5–7.5 Hz), difference of −3.18, 95% CI −3.57, −2.80; P = 0.03. No changes in spectral indices were seen for placebo. The maximum difference between pregabalin and placebo treated patients was seen in the parietal region, with a classification accuracy of 85.7% ( P = 0.009). Individual changes in EEG indices were correlated with changes in pain diary ( P = 0.04) and BPI pain composite scores ( P = 0.02). CONCLUSIONS Changes in spectral indices caused by slowing of brain oscillations were identified as a biomarker for the central analgesic effect of pregabalin. The developed methodology may provide perspectives to assess individual responses to treatment in personalized medicine.