Enhanced Temporal Coupling between Thalamus and Dorsolateral Prefrontal Cortex Mediates Chronic Low Back Pain and Depression

Abstract

Numerous neuroimaging studies have demonstrated that the brain plasticity is associated with chronic low back pain (cLBP). However, there is a lack of knowledge regarding the underlying mechanisms of thalamic pathways for chronic pain and psychological effects in cLBP caused by lumbar disc herniation (LDH). Combining psychophysics and magnetic resonance imaging (MRI), we investigated the structural and functional brain plasticity in 36 patients with LDH compared with 38 age- and gender-matched healthy controls. We found that (1) LDH patients had increased psychophysical disturbs (i.e., depression and anxiety), and depression (Beck-Depression Inventory, BDI) was found to be an outstanding significant factor to predict chronic pain (short form of the McGill Pain Questionnaire, SF-MPQ); (2) the LDH group showed significantly smaller fractional anisotropy values in the region of posterior corona radiate while gray matter volumes were comparable in both groups; (3) resting state functional connectivity analysis revealed that LDH patients exhibited increased temporal coupling between the thalamus and dorsolateral prefrontal cortex (DLPFC), which further mediate the relationship from chronic pain to depression. Our results emphasized that thalamic pathways underlying prefrontal cortex might play a key role in regulating chronic pain and depression of the pathophysiology of LDH.

Comorbid depressive symptoms can aggravate the functional changes of the pain matrix in patients with chronic back pain: A resting-state fMRI study

“…Follow-up mediation analysis then found that comorbid depressive symptoms could act as a mediator of the relationship between pain intensity and PDI scores, while the pain intensity could act as a mediator of the relationship between comorbid depressive symptoms and PDI scores. These results indicated that, similar to previous studies ( Li, 2021 ), depressive symptoms do affect the clinical characteristics associated with chronic pain. After determining the interaction, we next made two assumptions about the relationship between CBP and depression: (1) CBP and depression accelerate disease progression by affecting the neural basis of each other and (2) CBP and depression fundamentally share some of their neurological underpinnings.…”

“…For example, a preclinical study has identified a novel neural pathway from the dorsal raphe nucleus (involving 5-hydroxytryptamine projections) to the central nucleus of the amygdala (somatostatin-expressing neurons) that not only mediates depressive symptoms, but also affects painful symptoms ( Zhou et al, 2019 ). A neuroimaging study found that functional connectivity (FC) between the thalamus and dorsolateral prefrontal cortex (involved in the pain descending regulation system) modulated the relationship between depression and chronic low back pain ( Li, 2021 ). A study on heat pain sensitivity found that heat pain sensitivity was associated with thalamic, amygdala, cingulate cortex and sensory cortex activity in both chronic low back pain patients and depressed patients ( Rodriguez-Raecke et al, 2014 ).…”

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“…Followup mediation analysis then found that comorbid depressive symptoms could act as a mediator of the relationship between pain intensity and PDI scores, while the pain intensity could act as a mediator of the relationship between comorbid depressive symptoms and PDI scores. These results indicated that, similar to previous studies (Li, 2021), depressive symptoms do affect the clinical characteristics associated with chronic pain. After determining the interaction, we next made two assumptions about the relationship between CBP and depression: (1) CBP and depression accelerate disease progression by affecting the neural basis of each other and (2) CBP and depression fundamentally share some of their neurological underpinnings.…”

Regional brain atrophy in patients with chronic ankle instability: A voxel-based morphometry study

“…In the present study, voxel-wise correlation analysis showed that the left thalamus was positively correlated with FAAM-ADL score. The thalamus, which has extensive connections with the cerebral cortex, is known for its relay function and plays an important role in the top-down transmission and regulation of acute and chronic pain (Li et al, 2021 ). In addition, the thalamus plays a crucial part in motor control and motor learning (Sommer, 2003 ; Hasegawa et al, 2020 ).…”