A Dysfunctional Descending Pain Modulation System in Chronic Nonspecific Low Back Pain: A Systematic Review and ALE Meta-Analysis

Abstract

Pain, a physiological protective mechanism, turns into a complex dynamic neural response when it becomes chronic. The role of neuroplastic brain changes is more evident than the peripheral factors in the maintenance, modulation and amplification of chronic low back pain (cLBP). In this background, we summarise the brain changes in cLBP in a coordinate-based activation likelihood estimation (ALE) meta-analysis of previous functional magnetic resonance imaging (fMRI) studies. Databases ('PubMed', 'Scopus' and 'Sleuth') were searched till May 2022 and the activity pattern was noted under the 'without stimulation' and 'with stimulation' groups. A total of 312 studies were selected after removing duplicates. Seventeen (553 cLBP patients, 192 activation foci) studies were fulfilled the eligibility criteria and included in the 'without stimulation' group. Twelve statistically significant clusters are localized in the prefrontal cortex, primary somatosensory cortex, primary motor cortex, parietal cortex, anterior cingulate cortex, caudate, putamen, globus pallidus amygdala, occipital lobe, temporal lobe and associated white matter in this group. Ten studies (353 cLBP patients, 125 activation foci) were selected in the' with stimulation' groups. In this group, seven statistically significant clusters were found in the frontal cortex, orbitofrontal cortex, premotor cortex, parietal cortex, claustrum and insula. These statistically significant clusters indicate a probable imbalance in GABAergic modulation of brain circuits and dysfunction in the descending pain modulation system. This disparity in the pain neuro-matrix is the source of spontaneous and persisting pain in cLBP.

Keywords: Activation likelihood estimation meta-analysis; GABAergic circuitry in brain; chronic nonspecific low back pain; descending pain modulation system; functional magnetic resonance imaging.