Recent clinical advances in diabetic polyneuropathy

Horowitz, Steven H.

doi:10.1097/01.aco.0000245287.37905.c5

Cited by 15 publications

(12 citation statements)

References 54 publications

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“…5 In addition, there have been recent reviews in our specialty's symposium journals addressing mechanisms of chronic pain in the setting of diabetes. 6,7 Interestingly, these excellent reviews did not have any specific citations regarding the care of such patients receiving peripheral nerve blocks for surgical anesthesia-analgesia, presumably because such literature is sparse. There is animal evidence that nerve fibers of patients with diabetes may have a higher sensitivity to local anesthetics.…”

Section: Discussionmentioning

confidence: 99%

Diabetes Mellitus, Independent of Body Mass Index, Is Associated With a "Higher Success" Rate for Supraclavicular Brachial Plexus Blocks

Gebhard¹,

Nielsen²,

Pietrobon

et al. 2009

Regional Anesthesia and Pain Medicine

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We speculate that the "higher success" of SCB in patients with diabetes may be explained by: (i) higher sensitivity of diabetic nerve fibers to local anesthetics, (ii) possible unknown intraneural penetration before injection, and/or (iii) preexisting neuropathy with accompanying decreased sensation. In the absence of additional follow-up on these patients, these data should generate outcomes research addressing dose-response curves for patients with diabetes or at risk for diabetes.

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Section: Discussionmentioning

confidence: 99%

Diabetes Mellitus, Independent of Body Mass Index, Is Associated With a "Higher Success" Rate for Supraclavicular Brachial Plexus Blocks

Gebhard¹,

Nielsen²,

Pietrobon

et al. 2009

Regional Anesthesia and Pain Medicine

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“…Perceived to result from years of hyperglycemia, DPN is now known to manifest itself very early in the progression of the disease. Indeed, a less severe, but identical, form of DPN, known as impaired glucose tolerance neuropathy (IGTN), presents in the prediabetic state (16). Primary among the peripheral sensory neurons impacted by IGTN are the unmyelinated C-fibers, i.e., the same type that appears to mediate hypoglycemic detection at the portal vein.…”

Section: Discussionmentioning

confidence: 99%

Hypoglycemic detection at the portal vein is mediated by capsaicin-sensitive primary sensory neurons

Fujita¹,

Bohland²,

Sanchez‐Watts³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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To elucidate the type of spinal afferent involved in hypoglycemic detection at the portal vein, we considered the potential role of capsaicin-sensitive primary sensory neurons. Specifically, we examined the effect of capsaicin-induced ablation of portal vein afferents on the sympathoadrenal response to hypoglycemia. Under anesthesia, the portal vein was isolated in rats and either capsaicin (CAP) or the vehicle (CON) solution applied topically. During the same surgery, the carotid artery (sampling) and jugular vein (infusion) were cannulated. One week later, all animals underwent a hyperinsulinemic hypoglycemic clamp, with glucose (variable) and insulin (25 mU ⅐ kg Ϫ1 ⅐ min Ϫ1 ) infused via the jugular vein. Systemic hypoglycemia (2.76 Ϯ 0.05 mM) was induced by minute 75 and sustained until minute 105. By design, no significant differences were observed in arterial glucose or insulin concentrations between groups. When hypoglycemia was induced in CON, the plasma epinephrine concentration increased from 0.67 Ϯ 0.05 nM at basal to 36.15 Ϯ 2.32 nM by minute 105. Compared with CON, CAP animals demonstrated an 80% suppression in epinephrine levels by minute 105, 7.11 Ϯ 0.55 nM (P Ͻ 0.001). A similar response to hypoglycemia was observed for norepinephrine, with CAP values suppressed by 48% compared with CON. Immunohistochemical analysis of the portal vein revealed an 85% decrease in the number of calcitonin gene-related peptide-reactive nerve fibers following capsaicin-induced ablation. That the suppression in the sympathoadrenal response was comparable to our previous findings for total denervation of the portal vein indicates that hypoglycemic detection at the portal vein is mediated by capsaicin-sensitive primary sensory neurons.calcitonin gene-related peptide ; sympathoadrenal response; glucose sensing GLUCOSE SENSORS LOCATED IN THE PORTAL VEIN are now recognized as important mediators of the sympathoadrenal response to hypoglycemia. Masking these sensors via local glucose infusion, i.e., normalizing portal vein glycemia, in the presence of systemic hypoglycemia has been shown to substantially suppress the sympathetic response (9,10,13,14). Total denervation of the portal vein via topical application of phenol yields a similar diminished sympathoadrenal response to systemic hypoglycemia (15), indicating a critical role for portal vein afferents in glycemic detection. Glucose-sensitive afferents are known to reside in the hepatic vagus (22, 23), but recent studies suggest that these vagal afferents are not involved in hypoglycemic detection as it relates to neural-hormonal counterregulation (17, 18). In contrast, celiac superior mesenteric ganglionectomy (CSMG), which interrupts the spinal axis, has been shown to suppress the sympathoadrenal response to hypoglycemia (11).That hypoglycemic detection at the portal vein appears mediated by spinal afferents suggests that these glucose sensors may be capsaicin-sensitive primary sensory neurons (CPSN). Calcitonin gene-related peptide (CGRP) is recognized as a reliable m...

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“…Neuropathy is one of the most common complications of diabetes mellitus (Horowitz, 2006;Hughes, 2002;Sinnreich et al, 2005). Patients with diabetic neuropathy frequently experience a variety of aberrant sensations, such as spontaneous pain and hyperalgesia (increased pain responses to normally noxious stimuli) (Calcutt, 2004a;Marchettini et al, 2004;Tesfaye and Kempler, 2005).…”

Section: Introductionmentioning

confidence: 99%

Activation of dorsal horn microglia contributes to diabetes‐induced tactile allodynia via extracellular signal‐regulated protein kinase signaling

Tsuda¹,

Ueno²,

Kataoka³

et al. 2008

Glia

153

106

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Painful neuropathy is one of the most common complications of diabetes, one hallmark of which is tactile allodynia (pain hypersensitivity to innocuous stimulation). The underlying mechanisms of tactile allodynia are, however, poorly understood. Emerging evidence indicates that, following nerve injury, activated microglia in the spinal cord play a crucial role in tactile allodynia. However, it remains unknown whether spinal microglia are activated under diabetic conditions and whether they contribute to diabetes-induced tactile allodynia. In the present study, using streptozotocin (STZ)-induced diabetic rats that displayed tactile allodynia, we found several morphological changes of activated microglia in the dorsal horn. These included increases in Iba1 and OX-42 labeling (markers of microglia), hypertrophic morphology, the thickness and the retraction of processes, and in the number of activated microglia cells. Furthermore, in the dorsal horn of STZ diabetic rats, extracellular signal-regulated protein kinase (ERK) and an upstream kinase, Src-family kinase (SFK), both of which are implicated in microglial functions, were activated exclusively in microglia. Moreover, inhibition of ERK phosphorylation in the dorsal horn by intrathecal administration of U0126, an inhibitor of ERK activation, produced a striking alleviation of existing, long-term tactile allodynia of diabetic rats. We also found that a single administration of U0126 reduced the expression of allodynia. Together, these results suggest that activated dorsal horn microglia may be a crucial component of diabetes-induced tactile allodynia, mediated, in part, by the ERK signaling pathway. Thus, inhibiting microglia activation in the dorsal horn may represent a therapeutic strategy for treating diabetic tactile allodynia.

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Recent clinical advances in diabetic polyneuropathy

Abstract: Tight glycemic control, especially early in diabetes, is the best approach to minimizing the prevalence and severity of diabetic polyneuropathy and makes research into the deleterious effects of even mild hyperglycemia imperative.

Cited by 15 publications

References 54 publications

Diabetes Mellitus, Independent of Body Mass Index, Is Associated With a "Higher Success" Rate for Supraclavicular Brachial Plexus Blocks

Diabetes Mellitus, Independent of Body Mass Index, Is Associated With a "Higher Success" Rate for Supraclavicular Brachial Plexus Blocks

Hypoglycemic detection at the portal vein is mediated by capsaicin-sensitive primary sensory neurons

Activation of dorsal horn microglia contributes to diabetes‐induced tactile allodynia via extracellular signal‐regulated protein kinase signaling

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