Conditioned pain modulation recruits the descending pain modulatory system to inhibit spinal activity

Abstract Conditioned pain modulation (CPM) is a phenomenon where the perception of pain is reduced in the presence of a second painful stimulus. In rodents, a similar phenomenon involves descending control pathways that rely on the brainstem to modulate spinal cord activity while in humans, descending mechanisms including the spinal cord remain elusive. In this study, we applied functional MRI to simultaneously record brain and spinal cord responses during CPM in healthy participants. CPM developed over time and was associated with reduced activity in key pain-related brain regions and the spinal cord dorsal horn. Conversely, regions involved in descending pain modulation showed increased activity during CPM. Functional connectivity analyses revealed reduced coupling during CPM between spinal and descending control regions. Our findings demonstrate that CPM involves both the descending pain control system to inhibit spinal activity and bottom-up pain signalling of attenuated spinal responses.