PT  - JOURNAL ARTICLE
AU  - Alexandra Tinnermann
AU  - Christian Sprenger
AU  - Christian Büchel
TI  - The role of network interactions in opioid analgesia
AID  - 10.1101/2021.05.11.443635
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.05.11.443635
4099  - http://biorxiv.org/content/early/2021/05/13/2021.05.11.443635.short
4100  - http://biorxiv.org/content/early/2021/05/13/2021.05.11.443635.full
AB  - Opioids are potent and widely prescribed analgesic drugs with widespread cortical and subcortical targets. In particular, several brain regions such as the thalamus, the insula, the anterior cingulate cortex as well as the descending modulatory pain system including the spinal cord exhibit high µ-opioid receptor density and are thus crucial for opioid analgesia. Given the high degree of functional integration within these systems, we followed a network systems approach and investigated the entire pain system with a particular emphasis on the role of functional interactions underlying opioid analgesia. Male participants either received the rapid-acting µ-opioid receptor agonist remifentanil or saline while undergoing heat pain stimulation. In order to study the entire central pain system, we employed cortico-spinal fMRI which allows measuring BOLD responses simultaneously in the brain, brainstem and spinal cord and therefore enables investigating how opioids modulate interactions across the entire central pain system. Remifentanil reduced activity in several pain-related brain regions such as the insula, operculum and thalamus, but also in the spinal cord dorsal horn. In contrast, activity in the prefrontal cortex was higher during opioid treatment resulting from the absence of a pain-related deactivation. Importantly, activation in many of these regions correlated with individually perceived analgesia. Finally, functional interactions along the descending pain system, i.e. between the prefrontal cortex, periaqueductal gray and spinal cord were differentially modulated by remifentanil, indicating that coupling between the prefrontal cortex, brainstem and the spinal cord is a key mechanism of opioid analgesia.Competing Interest StatementThe authors have declared no competing interest.