Differential patterns of functional brain connectivity in long-term pain

<p dir="ltr">Long-term pain affects over a fifth of the population and is the leading cause of disability worldwide. The cause of developing long-term pain remains unknown for most of the patients. However, mechanistically it is known to involve aberrant signal processing in the central nervous system. Functional neuroimaging methods, like magnetic resonance imaging, have been proven helpful to better understand the dynamics of a brain in pain. Especially prevalent has been the observed differences in spontaneous low-frequency brain signal fluctuations that occur during rest.</p><p dir="ltr">This thesis focuses on resting-state functional magnetic resonance imaging to better understand the representation of pain in the brain. Functional magnetic resonance imaging data were pairwise correlated and compared between timepoints and groups depending on the research question. To be able to explore differential brain connectivity patterns and their association with pain chronification, the four studies included participants from (1) long-term pain cohorts, (2) previously treated long-term pain cohorts, and (3) healthy volunteers.</p><p dir="ltr">In a long-term follow-up for lumbar disc herniation in young individuals (Study I), we identified a distinct pattern of brain communication that was associated with receiving surgery in adolescence. A smaller group of individuals who received non- operative treatment for lumbar disc herniation in adolescence did not share these patterns. This finding is the first to demonstrate long-term effects of long-term pain conditions on the resting-state functional connectome, challenging the previously assumed reversibility upon successful treatment.</p><p dir="ltr">The brain network differences in Study I involved many connections between the canonical resting state networks "somatomotor" and "default mode". The same network pair was also significantly different in another comparison between patients treated with either genuine or sham surgery for sacroiliac joint pain (Study II). Study IV used a prospective approach to compare functional brain images at baseline between pain-free individuals and those who later developed a pain condition. In this comparison, a distinct pattern of brain communication was identified as well, which did not however contain the same extent of somatomotor-default mode network connections. This suggests that default mode network aberrations seen in long-term pain may reflect a disturbance of rest rather than a sign of neural pathophysiology in long-term pain. The growing database (described in Study III) will allow for future replications and investigations in larger samples. Soon, it may be possible to predict the development of long-term pain.</p><h3 dir="ltr">List of scientific papers</h3><p dir="ltr">I. Blomé, S., Kastrati, G., Pontén, S., Jonsjö, M., Lagerbäck, T., Skorpil, M., Möller, H., Lalouni, M., Fransson, P., Gerdhem, P., Thompson, W. H., & Jensen, K. (2025). Long-term effects on functional brain networks in adolescents treated for lumbar disc herniation. Molecular pain, 21.<br><a href="https://doi.org/10.1177/17448069251376189" rel="noreferrer" target="_blank">https://doi.org/10.1177/17448069251376189<br><br></a></p><p dir="ltr">II. Pontén, M., Thompson, W. H., Blomé, S., Vadenmark, V., Kaptchuk, T. J., Gerdhem, P., Lalouni, M., & Jensen, K. (2025). Comparing genuine and sham surgery for sacroiliac joint pain using self-assessments, pain testing, and neuroimaging. Pain reports, 10(6), e1340.<br><a href="https://doi.org/10.1097/pr9.0000000000001340" rel="noreferrer" target="_blank">https://doi.org/10.1097/pr9.0000000000001340<br><br></a></p><p dir="ltr">III. Gedin, F., Blomé, S., Kastrati, G., Lalouni, M., Åhs, F., Fransson, P., Rosén, J., Thompson, W. H., & Jensen, K. (2024). Predicting long-term pain by combining brain imaging, genetics and health questionnaire data with Swedish national registries using a prospective superstruct design. Molecular pain, 20.<br><a href="https://doi.org/10.1177/17448069241301628" rel="noreferrer" target="_blank">https://doi.org/10.1177/17448069241301628<br><br></a></p><p dir="ltr">IV. Blomé, S., Gedin, F., Kastrati, G., Rosén, J., Lalouni, M., Fransson, P., Thompson, W. H., & Jensen, K (2026). Intrinsic brain patterns associated with later symptomology - a step in predicting long-term pain. [Manuscript]</p>