Rethinking pain: how modern neuroscience is reshaping our understanding

Abstract

In 2017, the International Association for the Study of Pain defined nociplastic pain as pain arising from central nervous system plasticity without clear evidence of tissue injury or neuropathy. This “third category” challenges the conventional view that pain always results from identifiable pathology and can be eliminated by treating its cause. In parallel, the WHO introduced “primary chronic pain” in ICD-11, referring to pain persisting over three months without structural or neuropathic origins. To study underlying mechanisms, animal models have been developed in which transient inflammation triggers long-lasting, bilateral hypersensitivity without injury, allowing evaluation of centrally acting analgesics. Evidence from imaging and experimental studies shows that chronic pain involves widespread brain regions, particularly those linked to emotion, such as the parabrachial nucleus and central amygdala. A paradigm shift views pain as a survival-related signal generated by the brain, whose chronicity reflects maladaptive plasticity requiring therapeutic re-conceptualization.