Locus Coeruleus MR Measured Signal Intensity in Fibromyalgia Relative to Healthy Controls

Background: Fibromyalgia is a chronic pain condition without an established aetiology. However, noradrenergic dysfunction is a possible mechanism to explain the constellation of symptoms associated with fibromyalgia. Noradrenaline synthesis in the locus coeruleus (LC) results in a paramagnetic by-product, neuromelanin. Recently, a magnetic resonance imaging sequence sensitive to neuromelanin has been used to assay LC signal intensity, a proxy for noradrenergic system function. Here, we use MR imaging to investigate the noradrenergic-locus coeruleus system in participants with fibromyalgia and healthy controls. Methods: Forty-six participants with fibromyalgia and 41 healthy controls were recruited for a cross-sectional characterisation of LC signal intensity at 3 T, quantified from a 2D gradient echo acquisition. Participants completed the Revised Fibromyalgia Impact Questionnaire, as well as measures of anxiety, depression, sleep and the THINC-it cognitive battery. Results: An independent groups t-test revealed no differences in LC signal intensity between participants with fibromyalgia and healthy controls. For the participants with fibromyalgia, partial correlations accounting for age showed no association between LC signal intensity and fibromyalgia history, fibromyalgia symptom severity, anxiety, depression, insomnia or cognitive performance. Almost 90% of participants with fibromyalgia had been exposed to medications targeting noradrenergic function complicating the interpretation of these findings. Conclusions: LC signal intensity as measured by MR did not distinguish participants with fibromyalgia and healthy controls, nor was it associated with core fibromyalgia pain symptoms or associated symptoms. Dynamic measures of noradrenergic function may be required to understand noradrenergic contributions to fibromyalgia. Significance Statement: This study is the first report using MR measured signal intensity of the LC to examine noradrenergic function in participants with fibromyalgia. There was no difference in signal intensity when comparing patients to controls, nor did it associate with any symptoms or associated features of fibromyalgia. This suggests that lifetime noradrenergic function may not distinguish fibromyalgia.