Stable individual differences in habituation and sensitization to prolonged painful stimulation are underpinned by activity in the hippocampus, amygdala, and sensorimotor cortices.

Abstract

Acute pain serves to warn an organism of potential damage. Two plausible theoretical response scenarios for prolonged painful stimulation could be hypothesised: If the organism does not sense potential harm an individual may habituate. Whereas, if harm is possible, pain sensitization may be more probable. Examining how an individual adapts to prolonged stimulation will provide unique insight into the mechanisms underlying pain habituation and sensitisation and, potentially, a valuable perspective on the development of chronic pain. However, currently little is known about the stability of these individual differences or their underlying neural mechanisms. To address this, 85 participants completed an MRI session, involving a noxious stimulation task and a resting-state scan. Habituation/sensitization was operationalized as the slope of change in pain ratings across the task. Habituation was associated with increasing activity in the anterior hippocampus and amygdala over time, with sensitization associated with increasing activity in the sensorimotor cortices. These regions were then used as seeds for a resting-state functional connectivity analysis, which revealed that habituation was associated with higher connectivity between the hippocampus and ventromedial prefrontal cortex, as well as higher connectivity between sensorimotor regions and the hippocampus, amygdala, and insula cortex. We have shown that habituation/sensitization to pain is a stable trait underpinned by differential activity in brain regions supporting sensory processing and appraisal. The perspective of these stable phenotypical patterns could have clinical applications and potential for improving our understanding of the development of chronic pain.