Processing of Pain by the Developing Brain: Evidence of Differences Between Adolescent and Adult Females

Abstract

Adolescence is a sensitive period for both brain development and the emergence of chronic pain particularly in females. However, the brain mechanisms supporting pain perception during adolescence remain unclear. This study compares perceptual and brain responses to pain in female adolescents and adults to characterize pain processing in the developing brain. Thirty adolescent (ages 13-17) and thirty adult (ages 35-55) females underwent a functional MRI scan involving acute experimental pain. Participants received 12 ten-second noxious pressure stimuli which were applied to the left thumbnail at 2.5 and 4 kg/cm2, and rated pain intensity and unpleasantness on a visual analogue scale. We found a significant group-by-stimulus intensity interaction on pain ratings. Compared to adults, adolescents reported greater pain intensity and unpleasantness in response to 2.5 kg/cm2, but not 4 kg/cm2. Adolescents showed greater medial-lateral prefrontal cortex (PFC) and supramarginal gyrus activation in response to 2.5 kg/cm2, and greater medial PFC and rostral anterior cingulate responses to 4 kg/cm2. Adolescents showed augmented pain-evoked responses in the Neurologic Pain Signature and greater activation in the default mode (DMN) and ventral attention (VAN) networks. Also, the amygdala and associated regions played a stronger role in predicting pain intensity in adolescents, and activity in DMN and VAN regions more strongly mediated the relationship between stimulus intensity and pain ratings. This study provides the first evidence of augmented pain-evoked brain responses in healthy female adolescents involving regions important for nociceptive, affective and cognitive processing, in line with their augmented sensitivity to low-intensity noxious stimuli.