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.