(101) - Glial activation in chronic back pain: replication of the original observation and association with negative affect

Abstract

Using positron emission tomography and the radioligand [11C]PBR28, we recently demonstrated elevated brain levels of the 18 kDa translocator protein (TSPO)1, a glial activation marker, in chronic low back pain (cLBP) patients. Here we scanned additional cLBP patients (N = 11) and controls (N = 18) to determine the reproducibility of the initial findings, and interrogate the association between glial activation and negative affect. Standardized uptake value (SUV60-90 min) images, normalized by whole brain (SUVR), were used as an outcome metric. SUVR from thalamic and cortical (paracentral, precentral and postcentral) regions demonstrating significant group differences in the original study were compared between the new cohorts, controlling for the Ala147Thr TSPO polymorphism (which predicts binding affinity to [11C]PBR28), and injected dose (which was lower in the cLBP patients; P < .05). Regressions (controlling for genotype) were used to investigate the relationship between pain or Beck Depression Inventory [BDI] scores and SUVR from thalamus, as well as anterior insula (aINS), medial prefrontal cortex (mPFC), dorsal anterior cingulate cortex (dACC), regions-of-interest previously implicated in pain and negative affect. By comparing the new cohorts, we observed that patients demonstrate elevated thalamic SUVR (left: P = .048; right: P = .031), but not in cortical clusters; in the new patient cohort we did not replicate the previously-observed negative association between thalamic SUVR and clinical pain (P > .12). In the full patient sample (N = 21), BDI scores were higher than controls (5.33 ± 4.5 vs 1.35 ± 2.0; P < .001), and demonstrated significant positive associations with SUVR in aINS (P = .011), mPFC (P = .023), and dACC (P = .021), but not thalami (p's > .36). These results replicate our original observation that cLBP is associated with elevated thalamic levels of the glial marker TSPO. They also suggest a potential role of glial activation in negative affect. These observations further support the exploration of glial cells as therapeutic targets for chronic pain and related comorbidities. (1. Loggia, Brain 2015). Support: 1R21NS087472-01A1/1R01NS095937-01A1 (MLL).