Review Article

The Role of Stress Regulation on Neural Plasticity in Pain Chronification

Figure 1

Stress models of chronic pain. (a) The neurotoxic model, from the perspective of environmental influences, conceptualizes that chronic pain intensity or pain duration may lead to the maladaptive stress response, affecting the structure and function of the hippocampal formation and the parahippocampal gyrus (PHG) [32]. (b) The vulnerability model, from the perspective of genetic predispositions, conceptualizes that the small hippocampal volume as a vulnerable factor affects the levels of stress hormones, which in turn lead to enhanced activations of the parahippocampal gyrus and increased persistent pain intensity [32]. (c) The proposed integrated model, from the perspective of the combination of environmental influences and genetic predispositions, conceptualizes that vulnerable factors (e.g., properties of particular brain structures) and environmental factors (e.g., injury) codetermine the levels of basal cortisol, which result in the brain alterations. Thereafter, these physiological responses either return to normal levels with an adaptive manner or initiate a vicious cycle of cortisol dysfunction, brain reorganizations, and persistent pain state.
(a) Neurotoxic model
(b) Vulnerability model
(c) Proposed model of pain chronification