Effects of Chronic Pain Treatment on Altered Functional and Metabolic Activities in the Brain: A Systematic Review and Meta-Analysis of Functional Neuroimaging Studies

Front Neurosci. 2021 Jul 5;15:684926. doi: 10.3389/fnins.2021.684926. eCollection 2021.


Previous studies have identified altered brain changes in chronic pain patients, however, it remains unclear whether these changes are reversible. We summarized the neural and molecular changes in patients with chronic pain and employed a meta-analysis approach to quantify the changes. We included 75 studies and 11 of these 75 studies were included in the activation likelihood estimation (ALE) analysis. In the 62 functional magnetic resonance imaging (fMRI) studies, the primary somatosensory and motor cortex (SI and MI), thalamus, insula, and anterior cingulate cortex (ACC) showed significantly decreased activity after the treatments compared to baseline. In the 13 positron emission tomography (PET) studies, the SI, MI, thalamus, and insula showed significantly increased glucose uptake, blood flow, and opioid-receptor binding potentials after the treatments compared to baseline. A meta-analysis of fMRI studies in patients with chronic pain, during pain-related tasks, showed a significant deactivation likelihood cluster in the left medial posterior thalamus. Further studies are warranted to understand brain reorganization in patients with chronic pain compared to the normal state, in terms of its relationship with symptom reduction and baseline conditions.

Keywords: activation likelihood estimation; chronic pain; functional neuroimaging; meta-analysis; systematic review.

Publication types

  • Systematic Review