Functional brain reconfiguration during sustained pain

Lee, Jae‐Joong; Lee, Sung‐Woo; Lee, Dong Hee; Woo, Choong‐Wan

doi:10.7554/elife.74463

Cited by 11 publications

(5 citation statements)

References 85 publications

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“…These functional analyses all implicate the brain, providing genetic support to the current understanding of the pathophysiology of pain severity 93 . Genes predominantly expressed in the CNS, particularly in the cerebellum, cerebellar hemisphere, and cortex region, rather than in the DRG, appear to play a salient role in modulating the intensity of pain, consistent with prior associations of sustained chronic pain intensity with increased activity in these brain regions [94][95][96] . Our ndings are also consistent with prior reports 24,25,97,98 of enriched gene expression in brain that contribute to pain intensity in a dose-and time-dependent manner and may involve speci c neuronal processes in brain regions implicated in emotional processing 93 .…”

Section: Discussionsupporting

confidence: 74%

The genetic architecture of pain intensity in a sample of 598,339 U.S. veterans

Kranzler

Toikumo

Vickers-Smith

et al. 2023

Preprint

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Chronic pain is a common problem, with more than one-fifth of adult Americans reporting pain daily or on most days. It adversely affects quality of life and imposes substantial personal and economic costs. Efforts to treat chronic pain using opioids played a central role in precipitating the opioid crisis. Despite an estimated heritability of 25–50%, the genetic architecture of chronic pain is not well characterized, in part because studies have largely been limited to samples of European ancestry. To help address this knowledge gap, we conducted a cross-ancestry meta-analysis of pain intensity in 598,339 participants in the Million Veteran Program, which identified 125 independent genetic loci, 82 of which are novel. Pain intensity was genetically correlated with other pain phenotypes, level of substance use and substance use disorders, other psychiatric traits, education level, and cognitive traits. Integration of the GWAS findings with functional genomics data shows enrichment for putatively causal genes (n = 142) and proteins (n = 14) expressed in brain tissues, specifically in GABAergic neurons. Drug repurposing analysis identified anticonvulsants, beta-blockers, and calcium-channel blockers, among other drug groups, as having potential analgesic effects. Our results provide insights into key molecular contributors to the experience of pain and highlight attractive drug targets.

show abstract

Section: Discussionsupporting

confidence: 74%

The genetic architecture of pain intensity in a sample of 598,339 U.S. veterans

Kranzler

Toikumo

Vickers-Smith

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…. Genes predominantly expressed in the CNS, particularly in the cerebellum, cerebellar hemisphere, and cortex region, rather than in the DRG, appear to play a salient role in modulating the intensity of pain, consistent with prior associations of sustained chronic pain intensity with increased activity in these brain regions [94][95][96] . Our findings are also consistent with prior reports 24,25,97,98 of enriched gene expression in brain that contribute to pain intensity in a dose-and time-dependent manner and may involve specific neuronal processes in brain regions implicated in emotional processing .…”

supporting

confidence: 75%

The genetic architecture of pain intensity in a sample of 598,339 U.S. veterans

Toikumo

Vickers‐Smith

Jinwala³

et al. 2023

Preprint

View full text Add to dashboard Cite

Chronic pain is a common problem, with more than one-fifth of adult Americans reporting pain daily or on most days. It adversely affects quality of life and imposes substantial personal and economic costs. Efforts to treat chronic pain using opioids played a central role in precipitating the opioid crisis. Despite an estimated heritability of 25-50%, the genetic architecture of chronic pain is not well characterized, in part because studies have largely been limited to samples of European ancestry. To help address this knowledge gap, we conducted a cross-ancestry meta-analysis of pain intensity in 598,339 participants in the Million Veteran Program, which identified 125 independent genetic loci, 82 of which are novel. Pain intensity was genetically correlated with other pain phenotypes, level of substance use and substance use disorders, other psychiatric traits, education level, and cognitive traits. Integration of the GWAS findings with functional genomics data shows enrichment for putatively causal genes (n = 142) and proteins (n = 14) expressed in brain tissues, specifically in GABAergic neurons. Drug repurposing analysis identified anticonvulsants, beta-blockers, and calcium-channel blockers, among other drug groups, as having potential analgesic effects. Our results provide insights into key molecular contributors to the experience of pain and highlight attractive drug targets.

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“…Research indicates a positive correlation between spontaneous activity in SFG and perceived stress, with excessive perceived stress typically stemming from negative emotions such as anxiety and depression (54). The thalamus also plays a role in mediating noxious input to the cortex, and the functional reorganization of the SFG is crucial in top-down modulation of pain experiences, with strong FC between them potentially contributing to the sustained perception of pain (55). The thalamus and SFG's FC serve as a shared pathway in the experiences of breathlessness and pain perception (56, 57).…”

Section: Discussionmentioning

confidence: 99%

Functional connectivity alterations in the thalamus among patients with bronchial asthma

Wang,

Huang,

Dai

et al. 2024

Front. Neurol.

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ObjectiveBronchial Asthma (BA) is a common chronic respiratory disease worldwide. Earlier research has demonstrated abnormal functional connectivity (FC) in multiple cognition-related cortices in asthma patients. The thalamus (Thal) serves as a relay center for transmitting sensory signals, yet the modifications in the thalamic FC among individuals with asthma remain uncertain. This research employed the resting-state functional connectivity (rsFC) approach to explore alterations in thalamic functional connectivity among individuals with BA.Patients and methodsAfter excluding participants who did not meet the criteria, this study finally included 31 patients with BA, with a gender distribution of 16 males and 15 females. Subsequently, we recruited 31 healthy control participants (HC) matched for age, gender, and educational background. All participants underwent the Montreal Cognitive Assessment (MoCA) and the Hamilton Depression Rating Scale (HAMD) assessment. Following this, both groups underwent head magnetic resonance imaging scans, and resting-state functional magnetic resonance imaging (rs-fMRI) data was collected. Based on the AAL (Automated Anatomical Labeling) template, the bilateral thalamic regions were used as seed points (ROI) for subsequent rsFC research. Pearson correlation analysis was used to explore the relationship between thalamic functional connectivity and neuropsychological scales in both groups. After controlling for potential confounding factors such as age, gender, intelligence, and emotional level, a two-sample t-test was further used to explore differences in thalamic functional connectivity between the two groups of participants.ResultCompared to the HC group, the BA group demonstrated heightened functional connectivity (FC) between the left thalamus and the left cerebellar posterior lobe (CPL), left postcentral gyrus (PCG), and right superior frontal gyrus (SFG). Concurrently, there was a decrease in FC with both the Lentiform Nucleus (LN) and the left corpus callosum (CC). Performing FC analysis with the right thalamus as the Region of Interest (ROI) revealed an increase in FC between the right thalamus and the right SFG as well as the left CPL. Conversely, a decrease in FC was observed between the right thalamus and the right LN as well as the left CC.ConclusionIn our study, we have verified the presence of aberrant FC patterns in the thalamus of BA patients. When compared to HCs, BA patients exhibit aberrant alterations in FC between the thalamus and various brain areas connected to vision, hearing, emotional regulation, cognitive control, somatic sensations, and wakefulness. This provides further confirmation of the substantial role played by the thalamus in the advancement of BA.

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Functional brain reconfiguration during sustained pain

Cited by 11 publications

References 85 publications

The genetic architecture of pain intensity in a sample of 598,339 U.S. veterans

The genetic architecture of pain intensity in a sample of 598,339 U.S. veterans

The genetic architecture of pain intensity in a sample of 598,339 U.S. veterans

Functional connectivity alterations in the thalamus among patients with bronchial asthma

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