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We recently showed elevated levels of the 18kDa translocator protein (TSPO), a marker of neuroinflammation, in chronic low back pain patients (cLBP) compared to healthy controls(Loggia et al., 2015). Here, we test whether TSPO signal 1) can further subtype cLBP patients based on their clinical presentation, and 2) is associated with functional connectivity measures (because neuroinflammation may affect neuronal communication(Clark et al., 2015)). Patients with axial (cLBPAX; n=26; 43.7±16.6 y.o.) or radicular cLBP (cLBPRAD; n=28; 48.3±13.2 y.o.) received an integrated PET/MRI scan with the TSPO ligand [11C]PBR28. TSPO signal was quantified using standardized uptake values normalized by whole-brain signal (SUVR). Functional connectivity from primary somatosensory cortex (S1) (i.e., a region significant in the PET group comparison) was calculated from BOLD resting-state fMRI data. Connectivity and PET measures were compared across groups, correlated with and against each other and against the Fibromyalgia Screening Questionnaire (FSQ) scores, measure of pain “centralization”. Because two different scanners were used (BrainPET: 10 cLBPAX, 15 cLBPRAD; Biograph mMR: 16 cLBPAX, 13 cLBPRAD), scanner was included as a covariate in all analyses. Moreover, PET analyses also included Ala147Thr TSPO genotype, which predicts binding affinity to [11C]PBR28. In S1, TSPO signal and functional connectivity to the thalamus were: 1) higher in cLBPRAD compared to cLBPAX; 2) positively correlated with each other and 3) positively correlated with FSQ scores. Our data support the existence of different “neuroinflammatory signatures” in patients with different clinical presentation and that S1 neuroinflammatory signal is more pronounced in patients with higher pain “centralization”. Further, because S1 TSPO signal was correlated to S1-thalamus connectivity, our data support an association between neuroinflammatory changes and changes in neuronal communication, possibly indicating that the observed alterations reflect “neurogenic neuroinflammation”. Future studies are needed to determine whether neuroinflammation and related connectivity changes are possible therapeutic targets for chronic pain. 1R21NS087472-01A1; 1R01NS095937-01A; 1R01NS094306-01A1; W81XWH-14-1-0543.

The weak association between disability levels and “peripheral” (i.e., knee) findings suggests that central nervous system alterations may contribute to the pathophysiology of knee osteoarthritis (KOA). Here, we evaluated brain metabolite alterations in KOA patients, before and after total knee arthroplasty (TKA), using 1H-magnetic resonance spectroscopy (MRS). Thirty-four pre-surgical KOA patients and 13 healthy controls were scanned using a PRESS sequence (TE=30ms, TR=1.7s, voxel size=15 × 15 × 15mm). Additionally, a subset of patients (n=13) were re-scanned 4.1±1.6 (mean±SD) weeks post-TKA. When using Creatine (Cr)-normalized levels, pre-surgical KOA patients demonstrated lower N-acetylaspartate (NAA) (p≤0.01) and higher myoinositol (mIns) (p≤0.001), compared to healthy controls. The mIns levels were positively correlated with pain severity scores (r=0.37, p 0.05), irrespective of metric. Additionally, patients demonstrated post-surgical increases in Cr-normalized (p