2.1.2 Pain chronification from a biological perspective
As pain becomes chronic, the persistent activation of neural circuitry responsible for emotional processing can lead to further psychological and physical consequences, thereby worsening the perception of pain and its functional impact over time18. Neurobiologically, pain chronification requires disruptions in multiple complex pathways crucial for the neural processing of the pain experience. The mechanisms behind these disruptions are diverse19-21. At the cellular level, they involve glutamate excitotoxicity and reductions in inhibitory gamma-aminobutyric acid (GABA) levels, intensifying pain sensitivity in the periphery22. At the central nervous system level, shifts occur in the activation patterns of brain sensory cortical areas, gradually stressing limbic areas over time22. Eventually, this progression leads to neuroplastic changes, manifesting as a pathological rewiring of brain and spinal cord circuitry22. Notably, the activation of limbic areas plays a pivotal role in driving the development and escalation of chronic pain22. This process occurs through emotional activation, triggering the conversion of an acute sensory experience into an emotional, chronic and, debilitating one. Consequently, the individual’s experience of reality and decision-making become heavily impacted by the pain experience21. The fundamental link between pain and OUD stems from disruptions in the endogenous opioid system, which significantly influence the cellular and central nervous system changes described, with inappropriate neuronal rewiring and neuroplastic changes as a result, leading to perpetuation of pain and reward system imbalances19, 20.