Chronic Pain and Locus Coeruleus Integrity in Older Adults

Animal studies have suggested essential links between chronic pain and the locus coeruleus (LC), a brainstem region important for attention, but also pain and cognitive modulation. Recently developed MRI sequences now allow us to assess LC integrity in vivo. Our study examined the association between late midlife chronic pain and LC integrity in older adults via neuromelanin-contrast imaging. For this study, 484 community-dwelling men participating in the third wave of the Vietnam Era Twin Study of Aging (mean age=67.55; SD=2.60) underwent MRI-assessed neuromelanin signal detection in the LC. Contrast-to-noise ratios between LC regions and a pontine tegmentum reference region were used to assess LC integrity. The LC was subdivided into rostral and caudal portions. Rostral LC is more cortical-projecting, while caudal LC projects more to the cerebellum and spinal cord. Reporting of pain intensity on the SF-36 Bodily Pain scale from all three study waves was used to classify those with chronic pain, defined as moderate to severe pain across all three waves (n = 80, 16.5%). Bootstrapped multivariable regression models examined associations between late midlife chronic pain and LC integrity, adjusting for age, depressive symptoms, medical comorbidities, opioid usage, and twin clustering. Late midlife chronic pain was associated with .13 standard deviation lower rostral LC integrity (95%CI: -.63 to -.07). Meanwhile, late midlife chronic pain was associated with .12 standard deviation lower caudal LC integrity (95%CI: -.70 to -.21). Chronic pain across late midlife was associated with greater LC integrity in older adults. Pain was not differentially associated with rostral or caudal LC. Future work should seek to understand mechanisms underlying LC-pain associations in older adults, especially regarding the roles of inflammation and accumulating pathology. R01AG050595.