scholarly journals C-Fiber Assays in the Cornea vs. Skin

2019 ◽  
Vol 9 (11) ◽  
pp. 320
Author(s):  
Eric A. Moulton ◽  
David Borsook
Keyword(s):  
Confocal Microscopy ◽  
Nerve Fibers ◽  
High Threshold ◽  
C Fibers ◽  
Corneal Confocal Microscopy ◽  
C Fiber ◽  
Unmyelinated Nerve ◽  
Skin Biopsies ◽  
Patient Centric ◽  
Corneal Imaging

C-fibers are unmyelinated nerve fibers that transmit high threshold mechanical, thermal, and chemical signals that are associated with pain sensations. This review examines current literature on measuring altered peripheral nerve morphology and discusses the most relevant aspects of corneal microscopy, especially whether corneal imaging presents significant method advantages over skin biopsy. Given its relative merits, corneal confocal microscopy would seem to be a more practical and patient-centric approach than utilizing skin biopsies.

scholarly journals Vascular and neural mechanisms of ACh-mediated vasodilation in the forearm cutaneous microcirculation

2002 ◽  
Vol 92 (2) ◽  
pp. 780-788 ◽  
Author(s):  
Martin Berghoff ◽  
Madeera Kathpal ◽  
Sonja Kilo ◽  
Max J. Hilz ◽  
Roy Freeman
Keyword(s):  
Nerve Fibers ◽  
Axon Reflex ◽  
Doppler Flowmetry ◽  
Relative Contribution ◽  
C Fibers ◽  
Cutaneous Microcirculation ◽  
C Fiber ◽  
Dose Dependent Fashion ◽  
Cutaneous Perfusion ◽  
Dose Dependent

The relative contribution of endothelial vasodilating factors to acetylcholine (ACh)-mediated vasodilation in the forearm cutaneous microcirculation is unclear. The aims of this study were to investigate the contributions of prostanoids and cutaneous C fibers to basal cutaneous blood flow (CuBF) and ACh-mediated vasodilation. ACh was iontophoresed into the forearm, and cutaneous perfusion was measured by laser-Doppler flowmetry. To inhibit the production of prostanoids, four doses of acetylsalicylic acid (ASA; 81, 648, 972, and 1,944 mg) were administered orally. Cutaneous nerve fibers were blocked with topical anesthesia. Cyclooxygenase inhibition did not change basal CuBF or endothelium-mediated vasodilation to ACh. In contrast, ASA (972 and 1,944 mg) significantly reduced the C-fiber-mediated axon reflex in a dose-dependent fashion. Blockade of C-fiber function significantly reduced axon reflex-mediated vasodilation but did not affect basal CuBF or endothelium-dependent vasodilation. The findings suggest that prostanoids do not contribute significantly to basal CuBF or endothelium-dependent vasodilation in the forearm microcirculation. In contrast, prostanoids are mediators of the ACh-provoked axon reflex.

scholarly journals Automated Tortuosity Analysis of Nerve Fibers in Corneal Confocal Microscopy

2020 ◽  
Vol 39 (9) ◽  
pp. 2725-2737 ◽  
Author(s):  
Yitian Zhao ◽  
Jiong Zhang ◽  
Ella Pereira ◽  
Yalin Zheng ◽  
Pan Su ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Nerve Fibers ◽  
Corneal Confocal Microscopy

scholarly journals Rare human nerve growth factor-β mutation reveals relationship between C-afferent density and acute pain evaluation

2016 ◽  
Vol 116 (2) ◽  
pp. 425-430 ◽  
Author(s):  
Irene Perini ◽  
Mitra Tavakoli ◽  
Andrew Marshall ◽  
Jan Minde ◽  
India Morrison
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Fiber Density ◽  
Nerve Growth ◽  
Perceptual Evaluation ◽  
Pain Evaluation ◽  
C Fibers ◽  
Small Fiber ◽  
Corneal Confocal Microscopy ◽  
C Fiber

The rare nerve growth factor-β (NGFB) mutation R221W causes a selective loss of thinly myelinated fibers and especially unmyelinated C-fibers. Carriers of this mutation show altered pain sensation. A subset presents with arthropathic symptoms, with the homozygous most severely affected. The aim of the present study was to investigate the relationship between peripheral afferent loss and pain evaluation by performing a quantification of small-fiber density in the cornea of the carriers, relating density to pain evaluation measures. In vivo corneal confocal microscopy (CCM) was used to quantify C-fiber loss in the cornea of 19 R221W mutation carriers (3 homozygous) and 19 age-matched healthy control subjects. Pain evaluation data via the Situational Pain Questionnaire (SPQ) and the severity of neuropathy based on the Neuropathy Disability Score (NDS) were assessed. Homozygotes, heterozygotes, and control groups differed significantly in corneal C-nerve fiber density, with the homozygotes showing a significant afferent reduction. Importantly, peripheral C-fiber loss correlated negatively with pain evaluation, as revealed by SPQ scores. This study is the first to investigate the contribution of small-fiber density to the perceptual evaluation of pain. It demonstrates that the lower the peripheral small-fiber density, the lower the degree of reported pain intensity, indicating a functional relationship between small-fiber density and higher level pain experience.

scholarly journals The Expanded Bead Size of Corneal C-Nerve Fibers Visualized by Corneal Confocal Microscopy Is Associated with Slow Conduction Velocity of the Peripheral Nerves in Patients with Type 2 Diabetes Mellitus

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Fukashi Ishibashi ◽  
Rie Kojima ◽  
Miki Taniguchi ◽  
Aiko Kosaka ◽  
Harumi Uetake ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Conduction Velocity ◽  
Peripheral Nerves ◽  
Nerve Fibers ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Bead Size ◽  
Corneal Confocal Microscopy ◽  
Type 2 Diabetic

This study aims to establish the corneal nerve fiber (CNF) morphological alterations in a large cohort of type 2 diabetic patients and to investigate the association between the bead size, a novel parameter representing composite of accumulated mitochondria, glycogen particles, and vesicles in CNF, and the neurophysiological dysfunctions of the peripheral nerves. 162 type 2 diabetic patients and 45 healthy control subjects were studied in detail with a battery of clinical and neurological examinations and corneal confocal microscopy. Compared with controls, patients had abnormal CNF parameters. In particular the patients had reduced density and length of CNF and beading frequency and increased bead size. Alterations in CNF parameters were significant even in patients without neuropathy. The HbA1c levels were tightly associated with the bead size, which was inversely related to the motor and sensory nerve conduction velocity (NCV) and to the distal latency period of the median nerve positively. The CNF density and length positively correlated with the NCV and amplitude. The hyperglycemia-induced expansion of beads in CNF might be a predictor of slow NCV in peripheral nerves in type 2 diabetic patients.

Excitation of primate spinothalamic neurons by cutaneous C-fiber volleys

1979 ◽  
Vol 42 (5) ◽  
pp. 1354-1369 ◽  
Author(s):  
J. M. Chung ◽  
D. R. Kenshalo ◽  
K. D. Gerhart ◽  
W. D. Willis
Keyword(s):  
Dynamic Range ◽  
High Threshold ◽  
Mechanical Stimuli ◽  
Spinothalamic Tract ◽  
Noxious Heat ◽  
C Fibers ◽  
C Fiber ◽  
Excitatory Action ◽  
Low Threshold ◽  
Lateral Nucleus

1. The responses of spinothalamic tract cells in the lumbosacral spinal cords of anesthetized monkeys were examined following electrical stimulation of the sural nerve or the application of noxious thermal and mechanical stimuli to the skin on the lateral aspect of the foot. 2. The spinothalamic tract neurons were classified as wide dynamic range (WDR), high-threshold (HT), or low-threshold (LT) cells on the basis of their responses to mechanical stimuli. 3. All of the WDR and HT spinothalamic tract cells tested responded to volleys in A- and C-fibers. However, strong C-fiber responses were more common in HT than in WDR cells. 4. The responses atributed to C-fibers were graded with the size of the C-fiber volley. The latencies of the responses attributed to C-fibers indicated that the fastest afferents involved had a mean conduction velocity of 0.9 m/s. The responses remained after anodal blockade of conduction in A-fibers. 5. Temporal summation of the responses of spinothalamic tract cells was demonstrated both to brief trains of stimuli at 33 Hz and to single stimuli repeated at 1- to 2-s intervals. The latter phenomenon is often called "windup." 6. The responses of several spinothalamic tract cells to noxious heat pulses could still be elicited during anodal blockade of conduction in A-fibers. Similarly, it was possible to demonstrate an excitatory action of noxious mechanical stimuli despite interference with conduction in A-fibers by anodal current. 7. The cells investigated were located either in the marginal zone or in the layers of the dorsal horn equivalent to Rexed's laminae IV-VI in the cat. The cells were generally activated antidromically from the caudal part of the ventral posterior lateral nucleus of the thalamus.

Responses of intact and injured sural nerve fibers to cooling and menthol

2014 ◽  
Vol 111 (10) ◽  
pp. 2071-2083 ◽  
Author(s):  
Alina Teliban ◽  
Fabian Bartsch ◽  
Marek Struck ◽  
Ralf Baron ◽  
Wilfrid Jänig
Keyword(s):  
Sural Nerve ◽  
Nerve Fibers ◽  
Afferent Nerve ◽  
High Threshold ◽  
C Fibers ◽  
Afferent Nerve Fibers ◽  
Cold Sensitive ◽  
Low Threshold

Intact and injured cutaneous C-fibers in the rat sural nerve are cold sensitive, heat sensitive, and/or mechanosensitive. Cold-sensitive fibers are either low-threshold type 1 cold sensitive or high-threshold type 2 cold sensitive. The hypothesis was tested, in intact and injured afferent nerve fibers, that low-threshold cold-sensitive afferent nerve fibers are activated by the transient receptor potential melastatin 8 (TRPM8) agonist menthol, whereas high-threshold cold-sensitive C-fibers and cold-insensitive afferent nerve fibers are menthol insensitive. In anesthetized rats, activity was recorded from afferent nerve fibers in strands isolated from the sural nerve, which was either intact or crushed 6–12 days before the experiment distal to the recording site. In all, 77 functionally identified afferent C-fibers (30 intact fibers, 47 injured fibers) and 34 functionally characterized A-fibers (11 intact fibers, 23 injured fibers) were tested for their responses to menthol applied to their receptive fields either in the skin (10 or 20%) or in the nerve (4 or 8 mM). Menthol activated all intact ( n = 12) and 90% of injured ( n = 20/22) type 1 cold-sensitive C-fibers; it activated no intact type 2 cold-sensitive C-fibers ( n = 7) and 1/11 injured type 2 cold-sensitive C-fibers. Neither intact nor injured heat- and/or mechanosensitive cold-insensitive C-fibers ( n = 25) and almost no A-fibers ( n = 2/34) were activated by menthol. These results strongly argue that cutaneous type 1 cold-sensitive afferent fibers are nonnociceptive cold fibers that use the TRPM8 transduction channel.

scholarly journals In vivo corneal confocal microscopy and optical coherence tomography on eyes of participants with type 2 diabetes mellitus and obese participants without diabetes

2021 ◽  
Author(s):  
Noémi Tóth ◽  
David M. Silver ◽  
Szabolcs Balla ◽  
Miklós Káplár ◽  
Adrienne Csutak
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Optical Coherence Tomography ◽  
Type 2 Diabetes Mellitus ◽  
Confocal Microscopy ◽  
Nerve Fibers ◽  
Corneal Confocal Microscopy ◽  
Corneal Nerve

Abstract Purposes To examine corneal nerve and retinal nerve characteristics of participants with type 2 diabetes mellitus (T2DM) compared with obese participants without diabetes to discover potential nerve vulnerabilities. Methods All participants underwent a complete medical examination including a physical examination and blood sample tests. The ophthalmologic examination included best-corrected visual acuity, intraocular pressure, Schirmer test, tear film breakup time, slit-lamp examination, dilated fundus photography, in vivo corneal confocal microscopy (IVCCM), and optical coherence tomography (OCT). Results The study cohort consisted of 83 eyes of 83 individuals: a group of 44 participants with T2DM, and a control group of 39 obese participants with no history of diabetes. Comparing measurements on the two groups, participants with T2DM had lower values with statistical significance for retinal nerve fiber layer (RNFL) nasal superior thickness (p = 0.010) and three corneal nerve (CN) parameters: fiber length (p = 0.025), total branch density (p = 0.013), and fiber area (p = 0.009). There was a borderline significant difference in CN fiber width (p = 0.051) and RNFL nasal inferior thickness (p = 0.056). No other significant differences were observed in the IVCCM and OCT parameters. No statistically significant correlation was found between CN and RNFL parameters. Conclusions Progression from a pre-diabetic obese state to a T2DM condition might entail a loss or diminishment of certain corneal nerve fibers or retinal nerve fibers, but not necessarily a loss of both corneal and retinal nerve fibers simultaneously. Using IVCCM and OCT together enables monitoring of both corneal and retinal health of the eye.

scholarly journals Corneal Confocal Microscopy to Image Small Nerve Fiber Degeneration: Ophthalmology Meets Neurology

2021 ◽  
Vol 2 ◽  
Author(s):  
Ioannis N. Petropoulos ◽  
Gulfidan Bitirgen ◽  
Maryam Ferdousi ◽  
Alise Kalteniece ◽  
Shazli Azmi ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Diabetic Neuropathy ◽  
Nerve Fiber ◽  
Clinical Intervention ◽  
Nerve Fibers ◽  
Fiber Density ◽  
Corneal Confocal Microscopy ◽  
Intraepidermal Nerve Fiber Density ◽  
Corneal Nerve ◽  
Small Nerve

Neuropathic pain has multiple etiologies, but a major feature is small fiber dysfunction or damage. Corneal confocal microscopy (CCM) is a rapid non-invasive ophthalmic imaging technique that can image small nerve fibers in the cornea and has been utilized to show small nerve fiber loss in patients with diabetic and other neuropathies. CCM has comparable diagnostic utility to intraepidermal nerve fiber density for diabetic neuropathy, fibromyalgia and amyloid neuropathy and predicts the development of diabetic neuropathy. Moreover, in clinical intervention trials of patients with diabetic and sarcoid neuropathy, corneal nerve regeneration occurs early and precedes an improvement in symptoms and neurophysiology. Corneal nerve fiber loss also occurs and is associated with disease progression in multiple sclerosis, Parkinson's disease and dementia. We conclude that corneal confocal microscopy has good diagnostic and prognostic capability and fulfills the FDA criteria as a surrogate end point for clinical trials in peripheral and central neurodegenerative diseases.

Sensory receptors with unmyelinated (C) fibers innervating the skin of the rabbit's ear

1985 ◽  
Vol 54 (3) ◽  
pp. 491-501 ◽  
Author(s):  
V. K. Shea ◽  
E. R. Perl
Keyword(s):  
Mechanical Stimulation ◽  
Receptive Fields ◽  
High Threshold ◽  
Cutaneous Stimulation ◽  
Great Auricular Nerve ◽  
C Fibers ◽  
C Fiber ◽  
Back Ground ◽  
Low Threshold ◽  
Stimulation Of

The cutaneous receptive properties of unmyelinated (C) fibers of the rabbit's great auricular nerve were determined by single-unit recordings. The majority of C-fiber units could be excited by cutaneous stimulation, and such sensory units fell into three major categories on the basis of responses to mechanical and thermal stimulation of their cutaneous receptive fields: low-threshold mechanoreceptors, nociceptors, or specific thermoreceptors. The majority of afferent elements were nociceptive, and all nociceptors responded to strong mechanical stimulation. Three types of nociceptors could be distinguished by their responses to thermal stimuli. Polymodal nociceptors responded to heat with thresholds of 40-55 degrees C and typically displayed enhanced responses or sensitization after noxious heating of their receptive fields. High-threshold mechanoreceptors failed to respond promptly to heat before noxious cutaneous stimulation which, however, elicited subsequent back-ground activity or sensitivity to heat. A third type of nociceptor responded to cold but not to heat. Low-threshold mechanoreceptors were identified by their brisk responses to very gentle, slowly moving mechanical stimulation of their receptive fields, and were readily distinguished from any element classified as nociceptive by their lower mechanical thresholds. Rapid innocuous warming or cooling excited some of the low-threshold mechanoreceptors. Specific thermoreceptors, both warming and cooling types, were rare, insensitive to mechanical stimulation, and responded to very slight changes in temperature. In contrast to the sensitization to heat, which was characteristic of most nociceptors, specific warming receptors displayed depressed thermal responses after noxious heating of their receptive fields. These results provide further evidence of the similarity of C-fiber receptors innervating hairy skin of different species. Some differences from past reports and additional features are described.

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