Alterations in Somatomotor Network Functional Connectivity in Painful Diabetic Neuropathy—A Resting State Functional Magnetic Resonance Imaging Study

Selvarajah, Dinesh; Awadh, Mohammed; Gandhi, Rajiv; Wilkinson, Iain D.; Tesfaye, Solomon

doi:10.2337/db18-61-or

Cited by 4 publications

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“…Compared with the previous seedbased connectivity analysis with the thalamus as the single seed region, the network analysis in this study provided a comprehensive view through the entire pain-related network including (1) reduced connectivity in brain areas of the limbic, somatosensory, and cognition-integration systems, (2) correlations of the response to anti-neuralgia medications and the degree of skin nerve degeneration with reduced brain functional connectivity, particularly the insular connectivity, and (3) coupling of structural and functional connectivity reductions in the limbic, striatal, and cognition-integration areas. The current findings corroborate previous studies that documented reduced functional and structural connectivity in neuropathic pain of diabetes and trigeminal neuralgia, 14,36,37 providing evidence that links peripheral nerve degeneration with connectivity changes across the pain-related network.…”

Section: Discussionsupporting

confidence: 91%

“…rsfMRI is able to detect alterations in brain circuits that continuously encode and process spontaneous pain. 11,[13][14][15][16][17] Compared to stimulus-related fMRI, rsfMRI is more suitable for mapping the functional connectome of the brain that can be dynamically affected by different diseases. 18 We also acquired diffusion-weighted imaging (DWI) data to investigate the structural basis of the altered brain functional connectivity in SFN and further identify regions with correlated structural and functional dysconnectivity.…”

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confidence: 99%

“…In the current report, we investigated pain‐related brain alterations in pathologically confirmed SFN, applying the network‐based statistic (NBS) method 12 to analyze resting‐state fMRI (rsfMRI) data to identify functional dysconnectivity of the pain‐related brain network. rsfMRI is able to detect alterations in brain circuits that continuously encode and process spontaneous pain 11,13–17 . Compared to stimulus‐related fMRI, rsfMRI is more suitable for mapping the functional connectome of the brain that can be dynamically affected by different diseases 18 .…”

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confidence: 99%

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Limbic Connectivity Underlies Pain Treatment Response in Small‐Fiber Neuropathy

Chao

Hsieh

Lin

et al. 2022

Annals of Neurology

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Objective Small‐fiber neuropathy (SFN) is characterized by neuropathic pain due to degeneration of small‐diameter nerves in the skin. Given that brain reorganization occurs following chronic neuropathic pain, this study investigated the structural and functional basis of pain‐related brain changes after skin nerve degeneration. Methods Diffusion‐weighted and resting‐state functional MRI data were acquired from 53 pathologically confirmed SFN patients, and the structural and functional connectivity of the pain‐related network was assessed using network‐based statistic (NBS) analysis. Results Compared with age‐ and sex‐matched controls, the SFN patients exhibited a robust and global reduction of functional connectivity, mainly across the limbic and somatosensory systems. Furthermore, lower functional connectivity was associated with skin nerve degeneration measured by reduced intraepidermal nerve fiber density and better therapeutic response to anti‐neuralgia medications, particularly for the connectivity between the insula and the limbic areas including the anterior and middle cingulate cortices. Similar to the patterns of functional connectivity changes, the structural connectivity was robustly reduced among the limbic and somatosensory areas, and the cognition‐integration areas including the inferior parietal lobule. There was shared reduction of structural and functional connectivity among the limbic, somatosensory, striatal, and cognition‐integration systems: (1) between the middle cingulate cortex and inferior parietal lobule and (2) between the thalamus and putamen. These observations indicate the structural basis underlying altered functional connectivity in SFN. Interpretation Our findings provide imaging evidence linking structural and functional brain dysconnectivity to sensory deafferentation caused by peripheral nerve degeneration and therapeutic responses for neuropathic pain in SFN. ANN NEUROL 2023;93:655–667

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Section: Discussionsupporting

confidence: 91%

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confidence: 99%

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confidence: 99%

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Limbic Connectivity Underlies Pain Treatment Response in Small‐Fiber Neuropathy

Chao

Hsieh

Lin

et al. 2022

Annals of Neurology

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“…Several factors contribute to the development of neu-ropathic pain in diabetic neuropathy. AGE advanced glycation end products, HIF-1α hypoxia-induced factor 1α, PKC protein kinase C, TRPA1 transient receptor potential ankyrin 1, VGSC voltage-gated sodium channel, vWF von Willebrand factor are also described in patients with pDN: cortical atrophy within the somatomotor cortex and insula (Selvarajah et al 2018b;Shillo et al 2016), abnormal cortical interactions within the somatomotor network (Selvarajah et al 2018a), and increased cerebral blood flow in the anterior cingulate cortex (Watanabe et al 2018). It is still unknown whether the described CNS changes are only a response to afferent input of the peripheral nervous system or a primary mechanism responsible for the maintenance of pDN.…”

Section: Central Mechanisms Of Painful Diabetic Neuropathymentioning

confidence: 99%

Challenges of neuropathic pain: focus on diabetic neuropathy

et al. 2020

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Neuropathic pain is a frequent condition caused by a lesion or disease of the central or peripheral somatosensory nervous system. A frequent cause of peripheral neuropathic pain is diabetic neuropathy. Its complex pathophysiology is not yet fully elucidated, which contributes to underassessment and undertreatment. A mechanism-based treatment of painful diabetic neuropathy is challenging but phenotype-based stratification might be a way to develop individualized therapeutic concepts. Our goal is to review current knowledge of the pathophysiology of peripheral neuropathic pain, particularly painful diabetic neuropathy. We discuss state-of-the-art clinical assessment, validity of diagnostic and screening tools, and recommendations for the management of diabetic neuropathic pain including approaches towards personalized pain management. We also propose a research agenda for translational research including patient stratification for clinical trials and improved preclinical models in relation to current knowledge of underlying mechanisms.

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“…In painful-DPN, cortical atrophy is localized within the somatomotor cortex and insula. We have also demonstrated abnormal cortical interactions within the somatomotor network at rest which correlated with measures of pain and behavior in subjects with painful-DPN [147]. A recent study performed single-photon emission computed tomography to assess cerebral blood flow (CBF) in 24 subjects with painful- and 20 painless-DPN [148].…”

Section: Pathogenesis Of Painful-dpnmentioning

confidence: 99%

Painful and Painless Diabetic Neuropathies: What Is the Difference?

et al. 2019

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Purpose of Review The prevalence of diabetes mellitus and its chronic complications are increasing to epidemic proportions. This will unfortunately result in massive increases in diabetic distal symmetrical polyneuropathy (DPN) and its troublesome sequelae, including disabling neuropathic pain (painful-DPN), which affects around 25% of patients with diabetes. Why these patients develop neuropathic pain, while others with a similar degree of neuropathy do not, is not clearly understood. This review will look at recent advances that may shed some light on the differences between painful and painless-DPN. Recent Findings Gender, clinical pain phenotyping, serum biomarkers, brain imaging, genetics, and skin biopsy findings have been reported to differentiate painful- from painless-DPN. Summary Painful-DPN seems to be associated with female gender and small fiber dysfunction. Moreover, recent brain imaging studies have found neuropathic pain signatures within the central nervous system; however, whether this is the cause or effect of the pain is yet to be determined. Further research is urgently required to develop our understanding of the pathogenesis of pain in DPN in order to develop new and effective mechanistic treatments for painful-DPN.

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Alterations in Somatomotor Network Functional Connectivity in Painful Diabetic Neuropathy—A Resting State Functional Magnetic Resonance Imaging Study

Cited by 4 publications

References 0 publications

Limbic Connectivity Underlies Pain Treatment Response in Small‐Fiber Neuropathy

Limbic Connectivity Underlies Pain Treatment Response in Small‐Fiber Neuropathy

Challenges of neuropathic pain: focus on diabetic neuropathy

Painful and Painless Diabetic Neuropathies: What Is the Difference?

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