Dysregulation of Hedonic Processing in Chronic Pain: Insights from Preclinical Data

Abstract

Chronic pain has been increasingly recognized not only as a sensory disorder but also as a condition that profoundly disrupts affective and motivational processes. Preclinical research indicates that persistent nociceptive input drives maladaptive changes in brain reward circuits, particularly within the mesocorticolimbic dopamine system. These alterations contribute to anhedonia, diminished motivation, and aberrant reward valuation, core symptoms frequently observed in patients with chronic pain. In this review, we synthesize evidence from rodent models demonstrating how chronic pain impairs the hedonic experience and motivational aspects of reward through disrupted dopaminergic signaling, neuroinflammatory pathways, and opioid system dysregulation. We also highlight the temporal dynamics in the emergence of hedonic deficits, the sex-dependent mechanisms, and the interplay between pain and drug-seeking behaviors. Finally, we discuss how these findings inform the search for and predict early biomarkers and therapeutic targets aimed at restoring hedonic tone. A deeper understanding of the neurobiological basis of reward dysfunction in chronic pain may provide critical insights for developing more effective, mechanism-based interventions.