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  1. Article ; Online: Tapentadol and oxycodone affect resting-state functional brain connectivity: A randomized, placebo-controlled trial.

    Croosu, Suganthiya S / Frøkjaer, Jens B / Drewes, Asbjørn M / Hansen, Tine M

    Journal of neuroimaging : official journal of the American Society of Neuroimaging

    2021  Volume 31, Issue 5, Page(s) 956–961

    Abstract: Background and purpose: The changes in functional brain connectivity induced by treatment with analgesics are poorly investigated. Unfortunately, results from clinical studies investigating treatments in patients with pain are often confounded by co- ... ...

    Abstract Background and purpose: The changes in functional brain connectivity induced by treatment with analgesics are poorly investigated. Unfortunately, results from clinical studies investigating treatments in patients with pain are often confounded by co-medication and comorbidity. Thalamus is central in sensory processing, and we hypothesized that functional connectivity between thalamus and other brain areas in healthy volunteers was different in treatment with oxycodone, representing a pure opioid, compared to treatment with tapentadol, which has a dual effect on the opioidergic and adrenergic systems.
    Methods: Twenty-one healthy male volunteers were included in a randomized, double-blind, three-armed, placebo-controlled, cross-over study. All received tapentadol (50 mg extended release), oxycodone (10 mg extended release), or placebo twice daily for 14 days. Resting-state functional magnetic resonance imaging data were obtained before and after treatment. Seed-based functional connectivity analyses were performed between thalamus and other brain regions.
    Results: Compared to placebo, tapentadol increased functional connectivity between left thalamus and precentral cortex (P = .048), whereas oxycodone decreased functional connectivity between bilateral thalamus and the anterior cingulate cortex (P ≤ .005).
    Conclusions: This study has shown that the functional connectivity between thalamus and other brain areas central in pain processing was different for the tapentadol and oxycodone treatments compared to placebo. This supports that the two treatments exert different mechanism of action. Further studies with larger sample sizes need to be carried out in order to validate this.
    MeSH term(s) Analgesics, Opioid/pharmacology ; Brain/diagnostic imaging ; Cross-Over Studies ; Double-Blind Method ; Humans ; Male ; Oxycodone/pharmacology ; Phenols/pharmacology ; Tapentadol
    Chemical Substances Analgesics, Opioid ; Phenols ; Oxycodone (CD35PMG570) ; Tapentadol (H8A007M585)
    Language English
    Publishing date 2021-07-01
    Publishing country United States
    Document type Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
    ZDB-ID 1071724-9
    ISSN 1552-6569 ; 1051-2284
    ISSN (online) 1552-6569
    ISSN 1051-2284
    DOI 10.1111/jon.12902
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  2. Article ; Online: Gray Matter Brain Alterations in Type 1 Diabetes - Findings Based on Detailed Phenotyping of Neuropathy Status.

    Croosu, Suganthiya S / Hansen, Tine M / Røikjer, Johan / Mørch, Carsten D / Ejskjaer, Niels / Frøkjær, Jens B

    Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association

    2022  Volume 130, Issue 11, Page(s) 730–739

    Abstract: Aims: This study investigated brain structure in patients of type 1 diabetes with diabetic peripheral neuropathy (DPN) and type 1 diabetes with neuropathic pain and the associations to clinical, peripheral, and cognitive measurements.: Methods: Sixty ...

    Abstract Aims: This study investigated brain structure in patients of type 1 diabetes with diabetic peripheral neuropathy (DPN) and type 1 diabetes with neuropathic pain and the associations to clinical, peripheral, and cognitive measurements.
    Methods: Sixty individuals with type 1 diabetes and 20 healthy controls were included in the study. Nineteen individuals with type 1 diabetes and neuropathic pain, 19 with type 1 diabetes and DPN, 18 with type 1 diabetes without DPN, and 20 healthy controls were included in the brain analyses. We utilized structural brain magnetic resonance imaging to investigate total and regional gray matter volume.
    Results: Significant lower gray matter volume was found in type 1 diabetes with neuropathic pain and in type 1 diabetes without DPN compared to healthy controls (
    Conclusion: We demonstrated lower gray matter volume in individuals with type 1 diabetes regardless of the presence of DPN and neuropathic pain. Hence, central gray matter alteration was not associated with peripheral alterations.
    MeSH term(s) Humans ; Diabetes Mellitus, Type 1/complications ; Gray Matter/diagnostic imaging ; NAD ; Brain/diagnostic imaging ; Magnetic Resonance Imaging ; Neuralgia ; Diabetic Neuropathies/diagnostic imaging ; Diabetic Neuropathies/etiology
    Chemical Substances NAD (0U46U6E8UK)
    Language English
    Publishing date 2022-06-03
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1225416-2
    ISSN 1439-3646 ; 0947-7349
    ISSN (online) 1439-3646
    ISSN 0947-7349
    DOI 10.1055/a-1835-1877
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  3. Article ; Online: Alterations in Functional Connectivity of Thalamus and Primary Somatosensory Cortex in Painful and Painless Diabetic Peripheral Neuropathy.

    Croosu, Suganthiya S / Røikjer, Johan / Mørch, Carsten D / Ejskjaer, Niels / Frøkjær, Jens B / Hansen, Tine M

    Diabetes care

    2022  Volume 46, Issue 1, Page(s) 173–182

    Abstract: Objective: In this study we aimed to investigate the functional connectivity of brain regions involved in sensory processing in diabetes with and without painful and painless diabetic peripheral neuropathy (DPN) and the association with peripheral nerve ...

    Abstract Objective: In this study we aimed to investigate the functional connectivity of brain regions involved in sensory processing in diabetes with and without painful and painless diabetic peripheral neuropathy (DPN) and the association with peripheral nerve function and pain intensity.
    Research design and methods: In this cross-sectional study we used resting-state functional MRI (fMRI) to investigate functional brain connectivity of 19 individuals with type 1 diabetes and painful DPN, 19 with type 1 diabetes and painless DPN, 18 with type 1 diabetes without DPN, and 20 healthy control subjects. Seed-based connectivity analyses were performed for thalamus, postcentral gyrus, and insula, and the connectivity z scores were correlated with peripheral nerve function measurements and pain scores.
    Results: Overall, compared with those with painful DPN and healthy control subjects, subjects with type 1 diabetes without DPN showed hyperconnectivity between thalamus and motor areas and between postcentral gyrus and motor areas (all P ≤ 0.029). Poorer peripheral nerve functions and higher pain scores were associated with lower connectivity of the thalamus and postcentral gyrus (all P ≤ 0.043). No connectivity differences were found in insula (all P ≥ 0.071).
    Conclusions: Higher functional connectivity of thalamus and postcentral gyrus appeared only in diabetes without neuropathic complications. Thalamic/postcentral gyral connectivity measures demonstrated an association with peripheral nerve functions. Based on thalamic connectivity, it was possible to group the phenotypes of type 1 diabetes with painful/painless DPN and type 1 diabetes without DPN. The results of the current study support that fMRI can be used for phenotyping, and with validation, it may contribute to early detection and prevention of neuropathic complications.
    MeSH term(s) Humans ; Diabetic Neuropathies/diagnosis ; Diabetes Mellitus, Type 1/complications ; Somatosensory Cortex/diagnostic imaging ; Cross-Sectional Studies ; Pain/complications ; Magnetic Resonance Imaging/methods ; Thalamus/diagnostic imaging
    Language English
    Publishing date 2022-12-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 441231-x
    ISSN 1935-5548 ; 0149-5992
    ISSN (online) 1935-5548
    ISSN 0149-5992
    DOI 10.2337/dc22-0587
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  4. Article ; Online: Cognitive function in individuals with and without painful and painless diabetic polyneuropathy-A cross-sectional study in type 1 diabetes.

    Croosu, Suganthiya S / Gjela, Mimoza / Røikjer, Johan / Hansen, Tine M / Mørch, Carsten D / Frøkjaer, Jens B / Ejskjaer, Niels

    Endocrinology, diabetes & metabolism

    2023  Volume 6, Issue 4, Page(s) e420

    Abstract: Introduction: Previous studies suggest that cognitive impairment is more prevalent in individuals with painful and painless diabetic peripheral neuropathy (DPN). However, the current evidence is not well described. This study investigated cognitive ... ...

    Abstract Introduction: Previous studies suggest that cognitive impairment is more prevalent in individuals with painful and painless diabetic peripheral neuropathy (DPN). However, the current evidence is not well described. This study investigated cognitive function in adults with type 1 diabetes mellitus (T1DM) and the association to painful/painless DPN and clinical parameters.
    Methods: This cross-sectional, observational, case-control study included 58 participants with T1DM, sub-grouped into 20 participants with T1DM and painful DPN, 19 participants with T1DM and painless DPN, 19 participants with T1DM without DPN, and 20 healthy controls were included. The groups were matched for sex and age. The participants performed Addenbrooke's examination III (ACE-III), which assesses attention, memory, verbal fluency, language and visuospatial skills. Working memory was evaluated using an N-back task. Cognitive scores were compared between the groups and correlated to age, diabetes duration, HbA1c and nerve conduction measurements.
    Results: Compared to healthy controls, T1DM participants showed lower total ACE-III (p = .028), memory (p = .013) and language scores (p = .028), together with longer reaction times in the N-back task (p = .041). Subgroup analyses demonstrated lower memory scores in those with painless DPN compared with healthy controls (p = .013). No differences were observed between the three T1DM subgroups. Cognitive scores and clinical parameters were not associated.
    Conclusions: This study supports the notion of cognitive alterations in T1DM and indicates that cognitive function is altered in T1DM regardless of underlying neuropathic complications. The memory domain appears altered in T1DM, particularly in those with painless DPN. Further studies are needed to verify the findings.
    MeSH term(s) Adult ; Humans ; Diabetes Mellitus, Type 1/complications ; Diabetic Neuropathies/diagnosis ; Diabetic Neuropathies/etiology ; Cross-Sectional Studies ; Case-Control Studies ; Cognition
    Language English
    Publishing date 2023-04-18
    Publishing country England
    Document type Observational Study ; Journal Article
    ISSN 2398-9238
    ISSN (online) 2398-9238
    DOI 10.1002/edm2.420
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  5. Article ; Online: Altered functional connectivity between brain structures in adults with type 1 diabetes and polyneuropathy.

    Croosu, Suganthiya S / Hansen, Tine Maria / Brock, Birgitte / Mohr Drewes, Asbjørn / Brock, Christina / Frøkjær, Jens Brøndum

    Brain research

    2022  Volume 1784, Page(s) 147882

    Abstract: Objective: Alterations of the central nervous system are increasingly being recognized as a part of diabetes, especially in the thalamus and the default mode network (DMN). However, the functional involvement in diabetic peripheral neuropathy (DPN) is ... ...

    Abstract Objective: Alterations of the central nervous system are increasingly being recognized as a part of diabetes, especially in the thalamus and the default mode network (DMN). However, the functional involvement in diabetic peripheral neuropathy (DPN) is poorly understood. This study aimed to investigate functional connectivity of thalamus and DMN in individuals with DPN and the associations to clinical characteristics.
    Methods: Forty-seven type 1 diabetes mellitus (T1DM) individuals with DPN and 28 healthy controls underwent resting-state functional magnetic resonance imaging. Seed-to-voxel and ROI-to-ROI analyses were performed for thalamus and DMN. The connectivity for both thalamus and DMN were correlated to clinical parameters.
    Results: Alterations in the functional connectivity of the thalamus and DMN were observed in individuals with T1DM and DPN. Thalamus showed decreased connectivity to the middle frontal, superior frontal, and precentral cortex (all p
    Conclusion: Individuals with DPN had disrupted connectivity between thalamus/DMN and other brain structures and disrupted overall mean connectivity within DMN. Our findings support the existing knowledge of central nervous system involvement in diabetes and provide support for the involvement of thalamus and DMN in people with T1DM and DPN.
    MeSH term(s) Adult ; Brain/diagnostic imaging ; Brain Mapping/methods ; Diabetes Mellitus, Type 1/complications ; Humans ; Magnetic Resonance Imaging/methods ; Polyneuropathies
    Language English
    Publishing date 2022-03-11
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1200-2
    ISSN 1872-6240 ; 0006-8993
    ISSN (online) 1872-6240
    ISSN 0006-8993
    DOI 10.1016/j.brainres.2022.147882
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  6. Article: [No title information]

    Croosu, Suganthiya S. / Hansen, Tine M. / Røikjer, Johan / Mørch, Carsten D. / Ejskjaer, Niels / Frøkjær, Jens B.

    Experimental and Clinical Endocrinology & Diabetes

    2022  Volume 130, Issue 11, Page(s) 730–739

    Abstract: Aims: This study investigated brain structure in patients of type 1 diabetes with diabetic peripheral neuropathy (DPN) and type 1 diabetes with neuropathic pain and the associations to clinical, peripheral, and ... ...

    Abstract Aims: This study investigated brain structure in patients of type 1 diabetes with diabetic peripheral neuropathy (DPN) and type 1 diabetes with neuropathic pain and the associations to clinical, peripheral, and cognitive measurements.
    Methods: Sixty individuals with type 1 diabetes and 20 healthy controls were included in the study. Nineteen individuals with type 1 diabetes and neuropathic pain, 19 with type 1 diabetes and DPN, 18 with type 1 diabetes without DPN, and 20 healthy controls were included in the brain analyses. We utilized structural brain magnetic resonance imaging to investigate total and regional gray matter volume.
    Results: Significant lower gray matter volume was found in type 1 diabetes with neuropathic pain and in type 1 diabetes without DPN compared to healthy controls ( p =0.024 and p =0.019, respectively). Lower insula volume was observed in all three diabetes groups (all p ≤0.050). Thalamus and hippocampus volume was lower in type 1 diabetes with neuropathic pain, cerebellum volume was lower in type 1 diabetes with DPN, and somatosensory cortex volume was lower in type 1 diabetes without DPN (all p ≤0.018). Attenuated memory was associated with lower gray matter volume in type 1 diabetes with DPN. No associations were found between gray matter volume and clinical/peripheral measurements.
    Conclusion: We demonstrated lower gray matter volume in individuals with type 1 diabetes regardless of the presence of DPN and neuropathic pain. Hence, central gray matter alteration was not associated with peripheral alterations.
    Keywords Diabetes ; Magnetic resonance imaging ; Diabetic peripheral neuropathy ; Brain structure ; Brain volume alterations
    Language English
    Publishing date 2022-06-03
    Publisher Georg Thieme Verlag KG
    Publishing place Stuttgart ; New York
    Document type Article
    ZDB-ID 1225416-2
    ISSN 1439-3646 ; 0947-7349
    ISSN (online) 1439-3646
    ISSN 0947-7349
    DOI 10.1055/a-1835-1877
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