Temporal dynamics of hippocampal activity predict stable patterns of sensitization or habituation to noxious stimulation across sessions.

Abstract

Acute pain serves to warn an organism of potential damage. When nociceptive stimulation persists, two possible responses emerge: If no risk of harm is anticipated, habituation may occur. If harm is considered possible, pain sensitization is likely. An individuals adaptation to prolonged pain may provide insight into their ability to manage resources, and possibly their likelihood of developing chronic pain. Yet, little is known about the stability of these individual differences or their underlying neural mechanisms. Eighty-five participants undertook a repetitive noxious stimulation task and a resting-state scan in an MRI scanner, in a first session. They then completed the same task outside the scanner on three separate days. Pain adaptation was operationalized as the slope of change in pain ratings within session. Intraclass correlations were calculated between slopes across the four sessions, which demonstrated high stability and association with emotional disposition. Individuals who habituated to repeated stimuli showed increasing activity in the anterior hippocampus and amygdala, while individuals who sensitized showed increasing activity in the sensorimotor cortices. These clusters were then used as seeds in resting state analysis, with habituation associated with higher functional connectivity between hippocampus/amygdala and ventromedial prefrontal cortex(vmPFC), and higher connectivity between sensorimotor regions and the hippocampus, amygdala and insula cortex. Our findings suggest that pain adaptation is a stable phenotypic trait, which may have implications for the prediction of chronic pain. This study implicates neural sensory and appraisal systems in these stable responses, offering insight into the mechanisms underlying trait-like responses to prolonged nociceptive input.