A skin blister method to study epidermal nerves in peripheral nerve disease

Kennedy, William R.; Nolano, Maria; Wendelschafer‐Crabb, Gwen; Johnson, T.L.; Tamura, Eiji

doi:10.1002/(sici)1097-4598(199903)22:3<360::aid-mus9>3.0.co;2-j

Cited by 104 publications

(67 citation statements)

References 21 publications

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“…They provide histological data and can be regarded as the gold standard. However, skin biopsies are more invasive than electrical stimulation, and quantitative analysis is time consuming (44). In clinically advanced diabetic neuropathy, skin biopsies show dermal fiber loss.…”

Section: Other Methods To Assess Skin Innervation In Diabetesmentioning

confidence: 99%

Electrically Stimulated Axon Reflexes Are Diminished in Diabetic Small Fiber Neuropathies

et al. 2004

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Axon reflex mediated flare depends on the density and the function of cutaneous C-fibers and may be impaired in diabetic neuropathy. We induced neurogenic axon reflex flare by intracutaneous electrical stimulation and analyzed size and intensity of the flare on the dorsum of the foot and ventral thigh with laser Doppler imaging (LDI). We investigated 12 diabetic subjects with small fiber neuropathies (SFNs), 5 diabetic subjects without neuropathy (NO-Ns), and 14 healthy control subjects. Five of the normal subjects were reassessed after 12 months. In comparing patients with SFN to control subjects, we found that SFN flare size but not the intensity of vasodilation (flux) was reduced on the feet (P < 0.001) and thighs (P < 0.007). Furthermore, electrical thresholds for flare induction were increased (thighs P < 0.001 and feet P < 0.03). In NO-Ns, flare size at the feet (P < 0.02) and flux at both sites (thighs P < 0.001 and feet P < 0.002) were even increased. Test/ retest evaluation of our method revealed a good correlation (r ‫؍‬ 0.83, P < 0.004). Intracutaneous electrical stimulation of C-fibers and scanning the flare with LDI is a sensitive tool to reliably detect small fiber impairment in diabetic SFN subjects and even increased neuropeptide release in NO-Ns. Diabetes 53:769 -774, 2004 S mall fiber neuropathy (SFN) is a common complication in diabetes and other disorders. Clinical features of this disease often include pain and dysesthesia such as burning feet and neurovascular abnormalities (1). Despite its high incidence and clinical importance, there are only a few methods to quantify peripheral small fiber dysfunction. These include quantitative sensory testing (2), analysis of heart rate variability, assessment of sudomotor axon reflexes (3), or skin biopsies (4). However, availability of these procedures in clinical routine is limited and sensitivity of the psychophysical methods may be questioned.Analysis of axon reflexes is a simple and specific test for peripheral C-fiber function. Activation of nociceptive Cfibers in the skin by mechanical (5) or chemical stimuli (6,7) induces a spreading vasodilation, which is visible as a "flare response" surrounding the injured site (8). The flare depends on both the density and function of C-fiber nociceptors in the skin, in particular the subgroup of mechanoinsensitive "silent" nociceptors (9). The neuronal pathway of neurogenic vasodilation is organized as an axon reflex. Activation of peripheral C-nociceptors provokes nerve impulses, which are conducted centrally. At some branching points of the axonal tree these action potentials may invade peripheral branches (10), causing the release of vasodilatory neuropeptides from skin nerve terminals, e.g., calcitonin gene-related peptide and substance P (11,12).In previous studies, quantitative analysis of vasodilation in axon reflex flares (flare intensity) employing single channel laser Doppler flowmetry (5,13) was not sensitive enough to reliably distinguish between control subjects and patients with mild to mode...

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Section: Other Methods To Assess Skin Innervation In Diabetesmentioning

confidence: 99%

Electrically Stimulated Axon Reflexes Are Diminished in Diabetic Small Fiber Neuropathies

et al. 2004

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“…PGP 9.5 is a ubiquitin C-terminal hydrolase and is enriched in epidermal nerve fibers [32][33][34][35]. Multiple studies have emphasized the importance of intraepidermal nerve fiber density (IENFD) assessment using PGP-9.5 immunofluorescent staining in skin biopsy in the evaluation SFN [10,21,22,[36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55]. A punch biopsy is performed following established procedures [47], mostly 10 cm above the lateral malleolus after local anesthesia with 1% lidocaine.…”

Section: Skin Biopsymentioning

confidence: 99%

Small fiber neuropathy: a common and important clinical disorder

Hoitsma

Reulen

Baets

et al. 2004

Journal of the Neurological Sciences

187

135

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“…The minimally invasive method mentioned above for the quantitation of epidermal nerve fibers in skin biopsies [58,59] and blisters [60] is being adopted by several groups as a useful instrument for the morphological assessment of diabetic neuropathy. Recently, a new cutaneous nerve regeneration model using a capsaicin dressing was developed and validated in healthy controls and in diabetic subjects with and without neuropathy [61].…”

Section: Potential New Avenues and Future Prospectsmentioning

confidence: 99%

Advanced Diabetic Neuropathy: A Point of no Return?

Bouc̆ek¹

2006

Rev Diabetic Stud

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■ AbstractDiabetic peripheral neuropathy is the most common complication of long-standing diabetes mellitus which frequently results in clinically significant morbidities e.g. pain, foot ulcers and amputations. During its natural course it progresses from initial functional changes to late, poorly reversible, structural changes. Various interconnected pathogenetic concepts of diabetic neuropathy have been proposed based on metabolic and vascular factors, mostly derived from long-term hyperglycemia. These pathogenetic mechanisms have been targeted in several experimental and clinical trials. This review summarizes available, mainly morphological data from interventions designed to halt the progression or achieve the reversal of established diabetic neuropathy, which include the recovery of normoglycemia by pancreas or islet transplantation, polyol pathway blockade by aldose reductase inhibitors, mitigation of oxidative stress by the use of antioxidants or correction of abnormalities in essential fatty acid metabolism. Unfortunately, to date, no treatment based on pathogenic considerations has shown clear positive effects and thus early institution of optimal glycemic control remains the only available measure with proven efficacy in preventing or halting progression of diabetic neuropathy. Further experimental and clinical research employing objective reproducible parameters is clearly needed. Novel noninvasive or minimally invasive methods e.g. corneal confocal microscopy or epidermal nerve fiber counts may represent potentially useful instruments for the objective assessment of nerve damage and monitoring of treatment effects.

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A skin blister method to study epidermal nerves in peripheral nerve disease

Cited by 104 publications

References 21 publications

Electrically Stimulated Axon Reflexes Are Diminished in Diabetic Small Fiber Neuropathies

Electrically Stimulated Axon Reflexes Are Diminished in Diabetic Small Fiber Neuropathies

Small fiber neuropathy: a common and important clinical disorder

Advanced Diabetic Neuropathy: A Point of no Return?

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