Neural correlates of co-occurring pain and depression: an activation-likelihood estimation (ALE) meta-analysis and systematic review

Abstract

The relationship between pain and depression is thought to be bidirectional and the underlying neurobiology ‘shared’ between the two conditions. However, these claims are often based on qualitative comparisons of brain regions implicated in pain or depression, while focused quantitative studies of the neurobiology of pain-depression comorbidity are lacking. Particularly, the direction of comorbidity, i.e., pain with depression vs. depression with pain, is rarely addressed. In this systematic review (PROSPERO registration CRD42020219876), we aimed to delineate brain correlates associated with primary pain with concomitant depression, primary depression with concurrent pain, and equal pain and depression comorbidity, using activation likelihood estimation (ALE) meta-analysis. Neuroimaging studies published in English until the 28th of September 2021 were evaluated using PRISMA guidelines. A total of 70 studies were included, of which 26 reported stereotactic coordinates and were analysed with ALE. All studies were assessed for quality by two authors, using the National Institute of Health Quality Assessment Tool. Our results revealed paucity of studies that directly investigated the neurobiology of pain-depression comorbidity. The ALE analysis indicated that pain with concomitant depression was associated with the right amygdala, while depression with concomitant pain was related primarily to the left dorsolateral prefrontal cortex (DLPFC). We provide evidence that pain and depression have a cumulative negative effect on a specific set of brain regions, distinct for primary diagnosis of depression vs. pain.

The basolateral amygdala-anterior cingulate pathway contributes to depression-like behaviors and comorbidity with chronic pain behaviors in male mice

“…While similar lateralization has already been reported in the central amygdala during chronic pain 26 , 27 , especially at a later timepoint 28 , our results extend these findings to the BLA in the context of NPID. Also, a recent systematic review of 70 human imaging studies further supports our observation, as pain concomitant with depression was found to strongly associate with enhanced connectivity of the right amygdala, particularly with the prefrontal cortex 29 . Finally, as a complementary strategy to assess the connectivity of the ACC and the BLA, we took advantage of imaging data recently generated in our NPID model using resting-state functional Magnetic Resonance Imaging (rs-fMRI).…”

Galcanezumab for the treatment of chronic migraine and medication overuse headache: Real‐world clinical evidence in a severely impaired patient population

“…A study from Tassorelli's group demonstrated that patients with anxiety disorders are less likely to respond to anti‐CGRP mAbs (Bottiroli et al., 2021), confirming the results obtained in another study among CM sufferers treated with galcanezumab in 2020 (Smitherman et al., 2020). Pain and depression are processed by the same brain areas, thus determining a possible overlapping between the two conditions (Zheng et al., 2022), and this may explain why the two conditions are often correlated. Moreover, stating the incapability of the anti‐CGRP mAb to cross the BBB and to reach the abovementioned areas, it should be arguable that depressive symptoms may be refractory toward anti‐CGRP mAbs (Irimia et al., 2021).…”

Study of Risk Factors and Correlates of Migraine and Depression Comorbidity

“…Relevant studies have confirmed that the relationship between pain and depression is bidirectional. For the first time, a study (Zheng C J, Van Drunen S & Egorova-Brumley N., 2022) analyzed the neural correlation between pain and depression co-morbidities through ALE Meta-analysis. ALE analysis showed that pain accompanied by depression was related to the right amygdala, while depression accompanied by pain was mainly related to the left dorsolateral prefrontal cortex (DLPFC).…”