2022年 · 第102卷第35期

Although a large amount of evidence has confirmed that microglia and astrocytes have been found to play a crucial role in the occurrence and maintenance of persistent pain in animal model experiments, the role of glial cells in human pain disorders is still unknown. To this end, a new technique of positron emission tomography-magnetic resonance imaging (PET/MRI) and a recently developed radioligand (11) C-PBR28 were used to investigate, and the results showed elevated levels of transporter (TSPO), one of the markers of glial cell activation, in the brain of patients with chronic low back pain. Given that the polymorphism of Ala147Thr in the TSPO genotype affects the binding affinity to (11) C-PBR28, the authors of this study screened nine pairs of diseased groups and controls from a larger sample of subjects and compared them using a paired design. Each patient corresponded to a control group with TSPO gene polymorphism, age and sex matching (there were 7 Ala/Ala genotypes and 2 Ala/Thr genotypes, each group included 5 males and 4 females; median age difference: 1 year; age range: 29 to 63 years in the patient group and 28 to 65 years in the control group). The patient group had significantly higher standardized uptake values for multiple brain regions, including the thalamus and the presumed lumbar spine and leg somatosensory regions, compared with the control group, taking the whole brain as the standard. As predicted by animal studies, TSPO levels in the thalamus are inversely correlated with clinical pain and circulating levels of the pro-inflammatory cytokine interleukin-6, further demonstrating that TSPO expression plays a pain protective/anti-inflammatory role in humans. Due to the putative role of activated glial cells in the generation and/or maintenance of persistent pain, the present findings have important clinical implications and may help guide future pathophysiological studies of various persistent pain and pain management.

Alcohol use disorder (AUD) is a very common, refractory medical condition. Symptoms of AUD are caused by dysfunction of several neural circuits centered on the nucleus accumbens (NAc). Case reports and animal studies suggest that deep nucleus accumbens brain stimulation (NAc-DBS) treatment may be an effective harm reduction treatment for severe AUD. Six patients with severe refractory AUD received NAc-DBS, and safety measures and clinical results were recorded. Glucose metabolism in NAc was measured using positron emission tomography (FDG-PET) at baseline and at 6 months. Functional magnetic resonance imaging (fMRI) was used to characterize postoperative changes in functional connectivity of NAc to the rest of the brain, as well as the responsiveness of NAc and dorsal striatum to alcohol visual cues. The study is registered with ClinicalTrials.gov (NCT03660124). The degree of craving was reduced in all patients. Alcohol consumption, alcohol-related compulsions, and anxiety were significantly reduced at 12 months. There was no significant change in depression. FDG-PET analysis showed a decrease in NAc metabolism after 6 months, which was associated with an improvement in compulsive drinking behavior. Clinical improvement was associated with reduced functional connectivity between NAc and the visual symphysis cortex. Active deep brain stimulation (DBS) is associated with reduced activation of the dorsal striatum during passive viewing of alcohol-containing pictures. NAc-DBS is feasible and safe in patients with severe refractory AUD. It has been linked to a decrease in appetite and addictive behavior. The underlying mechanisms of this process are down-regulation of NAc, disruption of its functional connectivity to the visual symphyseal cortex, and interference with cue-evoked dorsal striatal reactivity.