The neural basis linking threat appraisal and pain outcomes in chronic pain: roles of the left DLPFC and PCC

<p indent="0mm">Chronic pain is defined as pain that persists or recurs for more than three months after the initial healing of a wound. In recent years, the rising prevalence of chronic pain among young people has become a significant concern, profoundly impacting their physical and mental well-being. While pain serves as an important signal of potential harm to health and survival, consistently interpreting it as a threat can contribute to the onset, persistence, and worsening of chronic pain. Threat appraisal, the process of evaluating pain as either actual or potential bodily damage, plays a crucial role in the development and maintenance of chronic pain. However, the neural mechanisms linking threat appraisal to chronic pain outcomes remain unclear. This study aimed to explore these neural correlates using the voxel-based morphometry (VBM) technique. Forty-eight young individuals with chronic pain (34 females, average age <sc>22.51 years,</sc> ranging from 19 to 30) completed questionnaires on demographics, threat appraisal, as well as chronic pain outcomes, including pain intensity (current, worst, and average pain intensity over the past three months) and pain interference (the negative impact of pain on daily activities, socialization and work over the past three months). Participants then underwent magnetic resonance imaging (MRI) to obtain structural brain images. Behavioral results revealed significant positive correlations between threat appraisal and both pain intensity and pain interference; specifically, higher threat appraisal levels were associated with more severe chronic pain outcomes. These results align with previous findings, and provide evidence for the fear-avoidance model of chronic pain. At the neuroimaging level, VBM analysis indicated that higher threat appraisal was linked to reduced gray matter volume in the left dorsolateral prefrontal cortex (DLPFC) and the left posterior cingulate cortex (PCC). Individuals with chronic pain exhibited decreased gray matter volume in these regions, suggesting potential impairments in pain inhibition, environmental threat appraisal, and emotional self-regulation, which may be linked to greater levels of threat appraisal, potentially creating a vicious circle. Further mediation analysis showed that threat appraisal mediated the relationships between gray matter volume in the left DLPFC and PCC and pain outcomes. Higher levels of threat appraisal were associated with reduced functioning in these brain areas, leading to increased sensitivity to perceived threats, diminished cognitive control over pain, and impaired emotional regulation. These factors may predispose individuals to adopt negative coping strategies, resulting in greater pain intensity and more significant disruption to daily life, which can hinder the healing process of chronic pain. In conclusion, the left DLPFC and PCC may serve as critical neural substrates linking threat appraisal to chronic pain outcomes. This research provides empirical evidence for the neural mechanisms connecting threat appraisal and chronic pain, supporting the development of early prevention strategies and interventions for managing chronic pain.