Microvascular Reactivity and Inflammatory Cytokines in Painful and Painless Peripheral Diabetic Neuropathy

Doupis, John; Lyons, Thomas E.; Wu, Szu-Huei; Gnardellis, Charalambos; Dinh, Thanh; Veves, Aristidis

doi:10.1210/jc.2008-2385

Cited by 221 publications

(173 citation statements)

References 33 publications

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“…Our results are in line with data from patients with peripheral diabetic neuropathy that assessed differences in immune mediator levels between individuals without and with pain (10). In that study, patients with painful neuropathy had higher circulating levels of CRP and sICAM-1, whereas no differences were found for TNF-a, and IL-6 was not measured (10).…”

Section: Discussionsupporting

confidence: 91%

“…In that study, patients with painful neuropathy had higher circulating levels of CRP and sICAM-1, whereas no differences were found for TNF-a, and IL-6 was not measured (10). The difference compared with our study regarding CRP is interesting given that we previously found associations between CRP and the MNSI score in a sample of diabetic patients (17), but not in the general older population (13), which suggests differences in risk factors of DSPN with respect to diabetic status.…”

Section: Discussionmentioning

confidence: 70%

“…One study of 77 patients with type 1 or type 2 diabetes and DSPN found higher systemic concentrations of C-reactive protein (CRP) and soluble intercellular adhesion molecule (sICAM)-1 in individuals with painful compared with painless DSPN. However, the selection of the study participants and the lack of adjustment for potential confounders precluded inferences to the general population (10).…”

mentioning

confidence: 99%

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Differential Association Between Biomarkers of Subclinical Inflammation and Painful Polyneuropathy: Results From the KORA F4 Study

et al. 2014

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OBJECTIVEInflammatory processes have been implicated in the pathogenesis of painful neuropathy in rodents, but the relationship between inflammatory biomarkers and painful distal sensorimotor polyneuropathy (DSPN) has not been assessed in population-based studies. Therefore, we investigated whether circulating levels of seven pro-and anti-inflammatory immune mediators were associated with painful DSPN in older individuals in a large population-based study. RESEARCH DESIGN AND METHODSThe study population consisted of individuals with painless (n = 337) and painful DSPN (n = 54) from a source population (n = 1,047) of men and women aged 61-82 years who participated in the German KORA F4 survey (2006)(2007)(2008). We measured circulating levels of seven immune mediators and assessed their associations with the presence of painful DSPN using multiple logistic regression models. RESULTSAfter adjustment for age and sex, we found positive associations between serum concentrations of the cytokine interleukin (IL)-6 and the soluble intercellular adhesion molecule (sICAM)-1 and painful DSPN (P = 0.004 and P = 0.005, respectively), whereas no associations were observed for C-reactive protein, IL-18, tumor necrosis factor-a, adiponectin, and IL-1 receptor antagonist (IL-1RA, P = 0.07-0.38). Associations between IL-6 and sICAM-1 and painful DSPN remained significant after additional adjustment for waist circumference, height, hypertension, cholesterol, smoking, alcohol intake, physical activity, history of myocardial infarction and/or stroke, presence of other neurological conditions, and use of nonsteroidal anti-inflammatory drugs (P = 0.005 and P = 0.016, respectively). CONCLUSIONSPainful DSPN is linked to systemic subclinical and vascular inflammation in the older population independent of anthropometric, lifestyle, and metabolic confounders.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 70%

mentioning

confidence: 99%

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Differential Association Between Biomarkers of Subclinical Inflammation and Painful Polyneuropathy: Results From the KORA F4 Study

et al. 2014

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“…Clinical trials in DPN patients with pain and without pain showed that the DPN with pain group had higher inflammation markers. Furthermore, DPN patients with pain and had more increased cytokine concentration compared with DPN patients without pain3. Another small cross‐sectional study4 showed that interleukin (IL)‐6 and IL‐10 were raised in some DPN patients, and correlated with abnormalities in large nerve fibers.…”

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confidence: 99%

Role of inflammatory biomarkers in diabetic peripheral neuropathy

Jin

Park

2018

J of Diabetes Invest

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“…Recent parallel studies by other groups suggest that microvascular dysfunction and the resulting production of reactive oxygen and nitrogen species may contribute to neuropathic pain (including chronic constriction injury (CCI) of the sciatic nerve 2,3,31 , painful diabetic neuropathy (PDN) 21,24,42,45,48,74 and chemotherapy-induced painful neuropathy (CIPN) 20,22,49,50 . Therefore, it is expected that treatments aimed at enhancing tissue oxygenation by reducing arterial vasospasm and capillary slow-flow/no-reflow will also relieve allodynia in animal models of nerve constriction, PDN and CIPN.…”

Section: Introductionmentioning

confidence: 99%

Topical Combinations Aimed at Treating Microvascular Dysfunction Reduce Allodynia in Rat Models of CRPS-I and Neuropathic Pain

Ragavendran

Laferrière

Xiao

et al. 2013

The Journal of Pain

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Growing evidence indicates that various chronic pain syndromes exhibit tissue abnormalities caused by microvasculature dysfunction in the blood vessels of skin, muscle or nerve. We tested whether topical combinations aimed at improving microvascular function would relieve allodynia in animal models of complex regional pain syndrome type I (CRPS-I) and neuropathic pain. We hypothesized that topical administration of either α 2 -adrenergic (α 2A ) receptor agonists or nitric oxide (NO) donors combined with either phosphodiesterase (PDE) or phosphatidic acid (PA) inhibitors would effectively reduce allodynia in these animal models of chronic pain. Single topical agents produced significant dose-dependent anti-allodynic effects in rats with chronic post- CIHR Author ManuscriptCIHR Author Manuscript CIHR Author Manuscript ischemia pain, and the anti-allodynic dose-response curves of PDE and PA inhibitors were shifted 2.5-10 fold leftward when combined with non-analgesic doses of α 2A receptor agonists or NO donors. Topical combinations also produced significant anti-allodynic effects in rats with sciatic nerve injury, painful diabetic neuropathy and chemotherapy-induced painful neuropathy. These effects were shown to be produced by a local action, lasted up to 6 h after acute treatment, and did not produce tolerance over 15 days of chronic daily dosing. The present results support the hypothesis that allodynia in animal models of CRPS-I and neuropathic pain is effectively relieved by topical combinations of α 2A or NO donors with PDE or PA inhibitors. This suggests that topical treatments aimed at improving microvascular function may reduce allodynia in patients with CRPS-I and neuropathic pain.Perspective-This article presents the synergistic anti-allodynic effects of combinations of α 2A or NO donors with PDE or PA inhibitors in animal models of CRPS-I and neuropathic pain. The data suggest effective clinical treatment of chronic neuropathic pain may be achieved by therapies that alleviate microvascular dysfunction in affected areas.

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Microvascular Reactivity and Inflammatory Cytokines in Painful and Painless Peripheral Diabetic Neuropathy

Abstract: Peripheral diabetic neuropathy is associated with increased biochemical markers of inflammation and endothelial dysfunction. Painful neuropathy is associated with further increase in inflammation and markers of endothelial dysfunction and preservation of the nerve axon reflex.

Cited by 221 publications

References 33 publications

Differential Association Between Biomarkers of Subclinical Inflammation and Painful Polyneuropathy: Results From the KORA F4 Study

Differential Association Between Biomarkers of Subclinical Inflammation and Painful Polyneuropathy: Results From the KORA F4 Study

Role of inflammatory biomarkers in diabetic peripheral neuropathy

Topical Combinations Aimed at Treating Microvascular Dysfunction Reduce Allodynia in Rat Models of CRPS-I and Neuropathic Pain

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