Chronic pain affects a substantial portion of the global population, significantly impacting quality of life and well-being. This condition involves complex mechanisms, including dysfunction of the autonomic nervous system, which plays a crucial role in pain perception. The insula, a key brain region involved in pain processing, plays a critical role in pain perception and modulation. Lesions in the insula can result in pain asymbolia, where pain perception remains intact but emotional responses are inappropriate. The insula is anatomically and functionally divided into anterior and posterior regions, with the posterior insula processing nociceptive input based on intensity and location before relaying it to the anterior insula for emotional mediation. Understanding the insula's intricate role in pain processing is crucial, as it is involved in encoding prediction errors and mediating emotional dimensions of pain perception. The focus of this review was on synthesizing existing literature on the role of the insula in chronic pain and associated structural changes. The goal was to integrate findings from various sources to provide a comprehensive overview of the topic. The search strategy included a combination of Medical Subject Headings (MeSH) and relevant keywords related to insula and chronic pain. The following databases were surveyed: PubMed, Embase, Scopus, and Web of Science. We identified a total of 2515 articles, and after following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline based on eligibility criteria, 46 articles were used to synthesize this review. Our study highlights the pivotal role of the insula in chronic pain processing and associated structural changes, integrating findings from diverse studies and neuroimaging investigations. Beyond mere pain sensation, the insula contributes to emotional awareness, attention, and salience detection within the pain network. Various chronic pain conditions reveal alterations in insular activity and connectivity, accompanied by changes in gray matter volume and neurochemical profiles. Interventions targeting the insula show promise in alleviating chronic pain symptoms. However, further research is needed to understand underlying mechanisms, which can aid in developing more effective therapeutic interventions for pain.
Keywords: anterior cingulate cortex; chronic pain; functional magnetic resonance imaging; insula; pain matrix.
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