A new minimally invasive technique to show nerve ischaemia in diabetic neuropathy

Ibrahim, Siti Fatimah; Harris, Nigel; Radatz, Matthias; Selmi, F; Rajbhandari, Satyan; Brady, Lesley; Jakubowski, Jan; Ward, J. D.

doi:10.1007/s001250051222

Cited by 51 publications

(38 citation statements)

References 31 publications

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“…Vascular defects also result in changes in endoneural vessels. Changes in blood flow correlate with changes in oxygen saturation (39) and reduced sural nerve endoneurial oxygen tension. These changes are potentiated by increased expression or action of vasoconstrictors such as endothelin and angiotensin and decreased activity of vasodilators such as prostacyclin, substance P, calcitonin gene-related peptide, endothelial-derived hyperpolarizing factor, and bradykinin (40).…”

Section: Statisticsmentioning

confidence: 93%

Pioglitazone Treatment Improves Nitrosative Stress in Type 2 Diabetes

et al. 2006

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OBJECTIVE -The purpose of this study was to determine the effect of 24 weeks of treatment with 45 mg/day pioglitazone on peripheral skin blood flow (SkBF) and skin nitric oxide (NO) production in vivo in patients with type 2 diabetes.RESEARCH DESIGN AND METHODS -This was a randomized, parallel, cross-over, double-blind, within-and between-subject study designed to compare vascular responses before and after treatment. We studied 12 subjects with type 2 diabetes (average age 58.6 Ϯ 30.8 years, HbA 1c 7.9 Ϯ 00.4%, BMI 31.3 Ϯ 1.2 kg/m 2 ). SkBF was measured using laser Doppler techniques in response to ischemia reperfusion and local skin warming, and NO production was assessed in vivo using an amperometric NO meter inserted directly into the skin. These measurements were performed before treatment and at 6 and 24 weeks.RESULTS -The SkBF response was not significantly improved after 24 weeks in either of the groups. NO production was significantly decreased in the pioglitazone-treated group in the basal condition (area under the curve 6.4 Ϯ 1.0 vs. 2.8 Ϯ 0.8, P Ͻ 0.01), after local heat stimulation at 40°C (12.9 Ϯ 2.2 vs. 5.7 Ϯ 1.7, P Ͻ 0.01), and after nociceptor stimulated flow with local heating at 44°C (36.4 Ϯ 6.3 vs. 16.6 Ϯ 3.4). Differences were not significant in the placebotreated group.CONCLUSIONS -Treatment of patients with type 2 diabetes with pioglitazone for 24 weeks reduced skin NO production, thus probably reducing nitrosative stress without a demonstrable effect on SkBF. Because nitrosative stress is considered to be a factor in the pathogenesis of neurovascular dysfunction, these findings warrant further investigation. Diabetes Care 29:869 -876, 2006W e have previously described both impaired peripheral vasoconstriction and vasodilatation in cutaneous vessels of people with diabetes, which strongly resembles the normal aging effects seen in peripheral vasculature (1). We have suggested both an endothelial and a neuronal component to these defects (2). The neuronal component is only activated at noxious temperatures (Ͼ40°C) or after tissue damage. Endothelial integrity is a major component under normal tissue demands for oxygenation after ischemia. Other investigators have also proposed the notion that there is specific damage to vascular endothelium and/or smooth muscle in diabetes, but localization of such a defect remains elusive.Insulin is a vasodilator hormone and facilitates endothelial release of nitric oxide (NO) and prostacyclin as well as upregulation of prostacyclin receptors on vascular smooth muscle (3). Resistance to the action of insulin could theoretically contribute to impaired neurovascular function. Jaap et al. (4) showed an endothelial or smooth muscle defect associated with insulin resistance that may precede the development of diabetes. We also showed that defective neurovascular function correlates with features of the metabolic syndrome, including insulin resistance, hypertension, dyslipidemia, and obesity (2). Diabetes is now recognized to be part of the metabolic syndrome an...

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Section: Statisticsmentioning

confidence: 93%

Pioglitazone Treatment Improves Nitrosative Stress in Type 2 Diabetes

et al. 2006

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“…The equipment and methods used in the measurement of epineurial intravascular oxygen saturation and blood flow have been validated and described in detail elsewhere [15,19].…”

Section: Methodsmentioning

confidence: 99%

“…As in our previous studies, great care was taken to avoid disturbing the nerve and its vasculature. A needle thermocouple was placed alongside the nerve to monitor temperature throughout the procedure [15].…”

Section: Methodsmentioning

confidence: 99%

“…Measurements were done using the Erlangen microlightguide spectrophotometer II (EMPHO II, Bodenseewerk Gerätetechnik, Überlingen, Germany) [15,19]. Light was shone onto the surface of the nerve through an endoscope and reflected light was collected, fed through a rotating interference filter disc and monochromatised in a range between 502 to 628 nm.…”

Section: Intravascular Oxygen Saturation Measurement (Hbo 2 %)mentioning

confidence: 99%

“…Impaired nerve blood flow and hypoxia are known to be important factors in the pathogenesis of DSP [14,15], although they have not previously been compared in subjects with chronic painful and painless DSP. However, there is reason to suspect that vascular factors could be important in pain.…”

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Increased sural nerve epineurial blood flow in human subjects with painful diabetic neuropathy

et al. 2003

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Aims/hypothesis. The pathogenesis of painful diabetic neuropathy remains unknown. As a consequence we still do not have any effective, rational treatments and a greater understanding of the mechanisms is urgently required. Previous studies have shown no consistent morphological differences in the nerves of patients with and without painful neuropathy. The aim of this study was to compare epineurial haemodynamics in patients with chronic painful and painless neuropathy. Methods. The techniques of microlightguide spectrophotometry and fluorescein angiography were used to measure epineurial intravascular oxygen saturation and blood flow respectively. Eleven patients with painful and eight with painless neuropathy were studied, with the groups matched carefully in terms of severity of neuropathy and diabetes control.Results. Intravascular oxygen saturation was higher in the painful neuropathy group compared to those without pain (median 73.8% vs 67.7%, respectively; p=0.021). Fluorescein rise time was also faster in those with painful symptoms (median 18.3 s vs 53.6 s; p=0.046) indicating higher epineurial blood flow in these subjects. Conclusion/interpretation. These results indicate that there are distinct differences in haemodynamics within the epineurium of the sural nerve in subjects with painful and painless neuropathy. Haemodynamic factors could therefore have an important role in the pathogenesis of neuropathic pain and might offer further insight into potential treatments for this distressing condition. [Diabetologia (2003) 46:934-939]

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Spotlight on Nerves: Portable Multispectral Optoacoustic Imaging of Peripheral Nerve Vascularization and Morphology

et al. 2023

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Various morphological and functional parameters of peripheral nerves and their vascular supply are indicative of pathological changes due to injury or disease. Based on recent improvements in optoacoustic image quality, the ability of multispectral optoacoustic tomography, to investigate the vascular environment and morphology of peripheral nerves is explored in vivo in a pilot study on healthy volunteers in tandem with ultrasound imaging (OPUS). The unique ability of optoacoustic imaging to visualize the vasa nervorum by observing intraneural vessels in healthy nerves is showcased in vivo for the first time. In addition, it is demonstrated that the label‐free spectral optoacoustic contrast of the perfused connective tissue of peripheral nerves can be linked to the endogenous contrast of hemoglobin and collagen. Metrics are introduced to analyze the composition of tissue based on its optoacoustic contrast and show that the high‐resolution spectral contrast reveals specific differences between nervous tissue and reference tissue in the nerve's surrounding. How this showcased extraction of peripheral nerve characteristics using multispectral optoacoustic and ultrasound imaging could offer new insights into the pathophysiology of nerve damage and neuropathies, for example, in the context of diabetes is discussed.

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A new minimally invasive technique to show nerve ischaemia in diabetic neuropathy

Cited by 51 publications

References 31 publications

Pioglitazone Treatment Improves Nitrosative Stress in Type 2 Diabetes

Pioglitazone Treatment Improves Nitrosative Stress in Type 2 Diabetes

Increased sural nerve epineurial blood flow in human subjects with painful diabetic neuropathy

Spotlight on Nerves: Portable Multispectral Optoacoustic Imaging of Peripheral Nerve Vascularization and Morphology

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