Morphine modifies the cingulate-operculum network underlying painful rectal evoked potentials

The effect of opioids on brain networks underlying rectal evoked potentials (EPs) has never been investigated. This study utilized brain source connectivity to explore whether morphine induced changes in brain networks underlying painful rectal EPs would reflect changes in pain scores due to morphine. Twenty healthy volunteers were included in this placebo-controlled cross-over study. Sensory and pain thresholds to electrically induced rectal stimulation were taken before (baseline) and 70 min after placebo/morphine (30 mg) administration. The stimulation intensity required to evoke moderate pain at baseline was employed for EPs. The pain score of this stimulation intensity was recorded again 70 min after placebo/morphine administration. 62-channel EPs were recorded for both arms. Amplitudes and latencies were analysed and brain source connectivity analysis was done. Changes in any of the parameters describing EPs were correlated to changes in subjective pain ratings. Morphine increased sensory and pain thresholds by 28.8% and 27.5% (P ≤ 0.02). The pain score corresponding to moderate pain at baseline was attenuated in both placebo and morphine arms by 14.5% and 37.5% (P < 0.05). There was a 33.9% reduction in EP amplitudes due to placebo (P < 0.05), whereas EP amplitudes remained stable due to morphine. A dominating cingulate-operculum network to rectal pain was seen. Cingulate source shifted anteriorly in the morphine arm (P < 0.001) and this shift was positively correlated to the change in the pain score (r = 0.6, P < 0.05). These findings indicate that visceral pain relief due to morphine is associated with reorganization within cingulate cortex, which may be used as a biomarker of opioid effects.