Recent translational work has shown that
fibromyalgia might be an autoimmune condition with pathogenic mechanisms mediated by a peripheral,
pain-inducing action of
immunoglobulin G (
IgG)
antibodies binding to satellite glia cells (SGC) in the dorsal root ganglia. A first clinical assessment of the postulated autoimmunity showed that
fibromyalgia subjects (FMS) had elevated levels of
antibodies against SGC (termed anti-SGC
IgG) compared to healthy controls and that anti-SGC
IgG were associated with a more severe disease status. The overarching aim of the current study was to determine whether the role of anti-SGC
IgG in driving
pain is exclusively through peripheral mechanisms, as indirectly shown so far, or could be attributed also to central mechanisms. To this end, we wanted to first confirm, in a larger cohort of FMS, the relation between anti-SGC
IgG and
pain-related clinical measures. Secondly, we explored the associations of these
autoantibodies with brain metabolite concentrations (assessed via magnetic resonance spectroscopy, MRS) and pressure-evoked cerebral
pain processing (assessed via functional magnetic resonance imaging, fMRI) in FMS.
Proton MRS was performed in the thalamus and rostral anterior cingulate cortex (rACC) of FMS and concentrations of a wide spectrum of metabolites were assessed. During fMRI, FMS received individually calibrated painful pressure stimuli corresponding to low and high
pain intensities. Our results confirmed a positive correlation between anti-SGC
IgG and clinical measures assessing condition severity. Additionally, FMS with high anti-SGC
IgG levels had higher
pain intensity and a worse disease status than FMS with low anti-SGC
IgG levels. Further, anti-SGC
IgG levels negatively correlated with metabolites such as
scyllo-inositol in thalamus and rACC as well as with total
choline and macromolecule 12 in thalamus, thus linking anti-SGC
IgG levels to the concentration of metabolites in the brain of FMS. However, anti-SGC
IgG levels in FMS were not associated with the sensitivity to pressure
pain or the cerebral processing of evoked pressure
pain. Taken together, our results suggest that anti-SGC
IgG might be clinically relevant for spontaneous, non-evoked
pain. Our current and previous translational and clinical findings could provide a rationale to try new antibody-related treatments in FMS.