AMIGO · A multi-ingredient brain function model predicting chronic pain in youth: a window into future well-being

Chronic pain is endemic and difficult to treat. The first surge occurs in adolescence, a critical period for brain development associated with high vulnerability. The number of adolescents with disabling pain has soared, and in most cases, pain persists into adulthood, strongly impacting long-term wellbeing. The impact of chronic pain in adolescence urgently calls for a better understanding of its causes, longitudinal predictors, and underlying biopsychosocial mechanisms. Psychosocial and physical stress in youth are critical risk factors for chronic pain in adolescence. Yet it is unknown how they interfere with individual brain physiology to predict who will develop chronic pain. I will use a longitudinal design involving adolescents undergoing major surgeries, coupled with an experimental neuroimaging approach, precision fMRI and machine learning methods to: (i) test the directionality of the association between risk factors, brain physiology and future onset of chronic pain (WP1); (ii) identify a neurophysiological multi-ingredient model that predicts, before surgery, who will (and via what mechanisms) develop chronic postsurgical pain (WP2); and, in a subset of pre-selected patients, (iii) test whether target neurophysiological pathways track pain along subacute and chronic pain phases and after treatment (WP3). I hypothesize that target brain pathways during pain, multisensory unpleasantness and self-evaluation in an affective context will: (i) synergistically predict future onset of pain at the individual adolescent level; (ii) be associated with major risk sources, (iii) exacerbate with chronic pain and attenuate after effective treatment. The results will lay foundational tools that can be used prospectively for early identification of (patho)physiology predicting future pain and patient subtypes. AMIGO has the potential for a profound impact on understanding, early detection, and mechanistically informed treatment recommendations in high-risk adolescents.