Dysregulated anterior insula reactivity as robust functional biomarker for chronic pain—Meta‐analytic evidence from neuroimaging studies

Neurobiological pain models propose that chronic pain is accompanied by neurofunctional changes that mediate pain processing dysfunctions. In contrast, meta‐analyses of neuroimaging studies in chronic pain conditions have not revealed convergent evidence for robust alterations during experimental pain induction. Against this background, the present neuroimaging meta‐analysis combined three different meta‐analytic approaches with stringent study selection criteria for case–control functional magnetic resonance imaging experiments during acute pain processing with a focus on chronic pain disorders. Convergent neurofunctional dysregulations in chronic pain patients were observed in the left anterior insula cortex. Seed‐based resting‐state functional connectivity based on a large publicly available dataset combined with a meta‐analytic task‐based approach identified the anterior insular region as a key node of an extended bilateral insula‐fronto‐cingular network, resembling the salience network. Moreover, the meta‐analytic decoding showed that this region presents a high probability to be specifically activated during pain‐related processes, although we cannot exclude an involvement in autonomic processes. Together, the present findings indicate that dysregulated left anterior insular activity represents a robust neurofunctional maladaptation and potential treatment target in chronic pain disorders.