Cortico-spinal coupling along descending pain system differentiates between opioid and saline treatment in healthy participants

Opioids are potent analgesic drugs with widespread cortical, subcortical
and spinal targets. In particular, the central pain system comprising
ascending and descending pain pathways has high opioid receptor densities
and is thus crucial for opioid analgesia. Here, we investigated effects of
the opioid remifentanil in a large sample (n=78) of healthy male
participants using combined cortico-spinal fMRI. This approach offers the
possibility to measure BOLD responses simultaneously in the brain and
spinal cord allowing us to investigate the role of cortico-spinal coupling
in opioid analgesia. Our data show that opioids altered activity in
regions involved in pain processing such as somatosensory regions
including the spinal cord and pain modulation such as prefrontal regions.
Moreover, coupling strength along the descending pain system, i.e. between
the medial prefrontal cortex, periaqueductal gray and spinal cord was
stronger in participants who reported stronger analgesia during opioid
treatment while the reversed pattern was observed in the control group.
These results indicate that coupling along the descending pain pathway is
a potential mechanism of opioid analgesia and can differentiate between
opioid analgesia and unspecific reductions in pain such as habituation.