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Journal of Neuromuscular Diseases 2021Small fiber neuropathy (SFN) is a disorder of the small myelinated Aδ-fibers and unmyelinated C-fibers [5, 6]. SFN might affect small sensory fibers, autonomic fibers... (Review)
Review
Small fiber neuropathy (SFN) is a disorder of the small myelinated Aδ-fibers and unmyelinated C-fibers [5, 6]. SFN might affect small sensory fibers, autonomic fibers or both, resulting in sensory changes, autonomic dysfunction or combined symptoms [7]. As a consequence, the symptoms are potentially numerous and have a large impact on quality of life [8]. Since diagnostic methods for SFN are numerous and its pathophysiology complex, this extensive review focusses on categorizing all aspects of SFN as disease and its diagnosis. In this review, sensitivity in combination with specificity of different diagnostic methods are described using the areas under the curve. In the end, a diagnostic work-flow is suggested based on different phenotypes of SFN.
Topics: Autonomic Nervous System Diseases; Biopsy; Female; Humans; Male; Nerve Fibers, Unmyelinated; Quality of Life; Small Fiber Neuropathy
PubMed: 33337383
DOI: 10.3233/JND-200490 -
Handbook of Clinical Neurology 2019The trigeminal sensory nerve fiber branches supply afferent information from the skin and mucous membranes of the face and head and the oral cavity regarding information... (Review)
Review
The trigeminal sensory nerve fiber branches supply afferent information from the skin and mucous membranes of the face and head and the oral cavity regarding information on temperature, touch, and pain. Under normal conditions, the trigeminal nerve serves to provide important information from nerve fibers and tissues using specialized receptors sensitive for irritant and painful stimuli. The current scientific consensus indicates that nerve endings responsible for chemical and thermal sensitivity of the skin and mucous membranes are the same nerves responsible for nociception. This "chemesthetic sense" allows many vertebrates to detect chemical agonists that induce sensations such as touch, burning, stinging, tingling, or changes in temperature. Research has been under way for many years to determine how exposure of the oral and/or nasal cavity to compounds that elicit pungent or irritant sensations can produce these sensations. In addition, these chemicals can alter other sensory information such as taste and smell to affect the flavor of foods and beverages. We now know that these 'chemesthetic molecules' are agonists of molecular receptors, which exist on primary afferent nerve fibers that innervate the orofacial area. However, under pathophysiologic conditions, over- or underexpression or activity of these receptors may lead to painful orotrigeminal syndromes. Some of these individual receptors are discussed in detail, including transient receptor potential channels and acid sensing ion channels, among others.
Topics: Animals; Humans; Mouth; Nerve Fibers; Pain; Skin; Taste; Trigeminal Nerve
PubMed: 31604548
DOI: 10.1016/B978-0-444-63855-7.00013-7 -
Journal of Neuroinflammation Mar 2017Dysregulation of the immune system in endometriotic milieus has been considered to play a pivotal role in the pathogenesis of endometriosis. Macrophage recruitment and... (Review)
Review
Dysregulation of the immune system in endometriotic milieus has been considered to play a pivotal role in the pathogenesis of endometriosis. Macrophage recruitment and nerve fiber infiltration are the two major characteristics of this aberrant immune environment. First, the recruitment of macrophages and their polarization phenotype within the endometriotic lesion have been demonstrated to facilitate the development and maintenance of endometriosis. M1 phenotype of macrophages has the capacity to secrete multiple cytokines for inflammatory response, while M2 macrophage possesses an opposite property that can mediate the process of immunosuppression and neuroangiogenesis. Upon secretion of multiple abnormal signal molecules by the endometriotic lesion, macrophages could alter their location and phenotype. These changes facilitate the accommodation of the aberrant microenvironment and the exacerbation of disease progression. Second, the infiltration of nerve fibers and their abnormal distribution are proved to be involved in the generation of endometriosis-associated pain and inflammatory response. An imbalance in sensory and sympathetic innervation and the abnormal secretion of different cytokines could mediate neurogenesis and subsequent peripheral neuroinflammation in endometriosis. Although endometriosis creates an inflammatory milieu promoting macrophage infiltration and an imbalanced innervation, interaction between macrophages and nerve fibers in this process remains unknown. The aim of this review is to highlight the role of macrophage and nerve interaction in endometriosis, where macrophage recruitment and neurogenesis can be the underlying mechanism of neuroinflammation and pathogenesis of endometriosis.
Topics: Animals; Endometriosis; Female; Humans; Macrophages; Nerve Fibers
PubMed: 28288663
DOI: 10.1186/s12974-017-0828-3 -
Eye (London, England) Feb 2017Retinal ganglion cell (RGC) loss is the hallmark of optic neuropathies, including glaucoma, where damage to RGC axons occurs at the level of the optic nerve head. In... (Review)
Review
Retinal ganglion cell (RGC) loss is the hallmark of optic neuropathies, including glaucoma, where damage to RGC axons occurs at the level of the optic nerve head. In experimental glaucoma, damage is assessed at the axon level (in the retinal nerve fibre layer and optic nerve head) or at the soma level (in the retina). In clinical glaucoma where measurements are generally limited to non-invasive techniques, structural measurements of the retinal nerve fibre layer and optic nerve head, or functional measurements with perimetry provide surrogate estimates of RGC integrity. These surrogate measurements, while clinically useful, are several levels removed from estimating actual RGC loss. Advances in imaging, labelling techniques, and transgenic medicine are making enormous strides in experimental glaucoma, providing knowledge on the pathophysiology of glaucoma, its progression and testing new therapeutic avenues. Advances are also being made in functional imaging of RGCs. Future efforts will now be directed towards translating these advances to clinical care.
Topics: Animals; Axons; Disease Models, Animal; Humans; Nerve Fibers; Optic Disk; Optic Nerve Diseases; Retinal Ganglion Cells; Staining and Labeling; Tomography, Optical Coherence; Visual Field Tests
PubMed: 28085141
DOI: 10.1038/eye.2016.295 -
Pain Nov 2023The mechanisms of pain in postherpetic neuralgia (PHN) are still unclear, with some studies showing loss of cutaneous sensory nerve fibers that seemed to correlate with...
The mechanisms of pain in postherpetic neuralgia (PHN) are still unclear, with some studies showing loss of cutaneous sensory nerve fibers that seemed to correlate with pain level. We report results of skin biopsies and correlations with baseline pain scores, mechanical hyperalgesia, and the Neuropathic Pain Symptom Inventory (NPSI) in 294 patients who participated in a clinical trial of TV-45070, a topical semiselective sodium 1.7 channel (Nav1.7) blocker. Intraepidermal nerve fibers and subepidermal Nav1.7 immunolabeled fibers were quantified in skin punch biopsies from the area of maximal PHN pain, as well as from the contralateral, homologous (mirror image) region. Across the entire study population, a 20% reduction in nerve fibers on the PHN-affected side compared with that in the contralateral side was noted; however, the reduction was much higher in older individuals, approaching 40% in those aged 70 years or older. There was a decrease in contralateral fiber counts as well, also noted in prior biopsy studies, the mechanism of which is not fully clear. Nav1.7-positive immunolabeling was present in approximately one-third of subepidermal nerve fibers and did not differ on the PHN-affected vs contralateral sides. Using cluster analysis, 2 groups could be identified, with the first cluster showing higher baseline pain, higher NPSI scores for squeezing and cold-induced pain, higher nerve fiber density, and higher Nav1.7 expression. While Nav1.7 varies from patient to patient, it does not seem to be a key pathophysiological driver of PHN pain. Individual differences in Nav1.7 expression, however, may determine the intensity and sensory aspects of pain.
Topics: Humans; Aged; Neuralgia, Postherpetic; Skin; Neuralgia; Administration, Cutaneous; Nerve Fibers
PubMed: 37366590
DOI: 10.1097/j.pain.0000000000002950 -
BioMed Research International 2017Recently, in vivo confocal microscopy is used to examine the human corneal nerve fibers morphology. Corneal nerve fiber architecture and its role are studied in healthy... (Review)
Review
Recently, in vivo confocal microscopy is used to examine the human corneal nerve fibers morphology. Corneal nerve fiber architecture and its role are studied in healthy and pathological conditions. Corneal nerves of rats were studied by nonspecific acetylcholinesterase (NsAchE) staining. NsAchE-positive subepithelial (stromal) nerve fiber has been found to be insensitive to capsaicin. Besides, NsAchE-negative but capsaicin-sensitive subbasal nerve (leash) fibers formed thick mesh-like structure showing close interconnections and exhibit both isolectin B4- and transient receptor potential vanilloid channel 1- (TRPV1-) positive. TRPV1, TRPV3, TRPA (ankyrin) 1, and TRPM (melastatin) 8 are expressed in corneal nerve fibers. Besides the corneal nerve fibers, the expressions of TRPV (1, 3, and 4), TRPC (canonical) 4, and TRPM8 are demonstrated in the corneal epithelial cell membrane. The realization of the importance of TRP channels acting as polymodal sensors of environmental stresses has identified potential drug targets for corneal disease. The pathophysiological conditions of corneal diseases are associated with disruption of normal tissue innervation, especially capsaicin-sensitive small sensory nerve fibers. The relationships between subbasal corneal nerve fiber morphology and neurotrophic keratopathy in corneal diseases are well studied. The recommended treatment for neurotrophic keratopathy is administration of preservative free eye drops.
Topics: Acetylcholinesterase; Animals; Capsaicin; Cornea; Corneal Diseases; Epithelium, Corneal; Humans; Nerve Fibers; Rats; TRPA1 Cation Channel; TRPM Cation Channels; TRPV Cation Channels
PubMed: 29238714
DOI: 10.1155/2017/3242649 -
PloS One 2021Clinical comparisons do not usually take laterality into account and thus may report erroneous or misleading data. The concept of laterality, well evaluated in brain and...
BACKGROUND AND PURPOSE
Clinical comparisons do not usually take laterality into account and thus may report erroneous or misleading data. The concept of laterality, well evaluated in brain and motor systems, may also apply at the level of peripheral nerves. Therefore, we sought to evaluate the extent to which we could observe an effect of laterality in MRI-collected white matter indices of the sciatic nerve and its two branches (tibial and fibular).
MATERIALS AND METHODS
We enrolled 17 healthy persons and performed peripheral nerve diffusion weighted imaging (DWI) and magnetization transfer imaging (MTI) of the sciatic, tibial and fibular nerve. Participants were scanned bilaterally, and findings were divided into ipsilateral and contralateral nerve fibers relative to self-reporting of hand dominance. Generalized estimating equation modeling was used to evaluate nerve fiber differences between ipsilateral and contralateral legs while controlling for confounding variables. All findings controlled for age, sex and number of scans performed.
RESULTS
A main effect of laterality was found in radial, axial, and mean diffusivity for the tibial nerve. Axial diffusivity was found to be lateralized in the sciatic nerve. When evaluating mean MTR, a main effect of laterality was found for each nerve division. A main effect of sex was found in the tibial and fibular nerve fiber bundles.
CONCLUSION
For the evaluation of nerve measures using DWI and MTI, in either healthy or disease states, consideration of underlying biological metrics of laterality in peripheral nerve fiber characteristics need to considered for data analysis. Integrating knowledge regarding biological laterality of peripheral nerve microstructure may be applied to improve how we diagnosis pain disorders, how we track patients' recovery and how we forecast pain chronification.
Topics: Adolescent; Diffusion Tensor Imaging; Female; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Nerve Fibers; Peripheral Nerves; Young Adult
PubMed: 34914714
DOI: 10.1371/journal.pone.0260256 -
Acta Obstetricia Et Gynecologica... 2009The assessment and diagnosis of endometriosis remain elusive targets. Patient and medical-related factors add to delays in the detection and treatment. Recently,... (Review)
Review
The assessment and diagnosis of endometriosis remain elusive targets. Patient and medical-related factors add to delays in the detection and treatment. Recently, investigators have revealed specific nerve fibers present in endometriotic tissue, with existing parallels between density and pain severity. The aim of this review is to compile a comprehensive review of existing literature on endometriosis-related nerve fiber detection, and the effects of medical therapy on these neural fibers. We performed a systematic literature-based review using Medline and PubMed of nerve fibers detected in eutopic endometrium, endometriotic lesions, and the peritoneum. Various arrangements of significant medical terms and phrases consisting of endometriosis, pelvic pain, nerve fiber detection/density in endometriosis, and diagnoses methodology, including treatment and detection were applied in the search. Subsequent references used were cross-matched with existing sources to compile all additional similar reports. Similar nerve fibers were detected within lesions, endometrium, and myometrium, though at varying degrees of density. Hormonal therapy is widely used to treat endometriosis and was shown to be related to a reduction in fiber density. A direct result of specific nerve fiber detection within eutopic endometrial layers points to the use of a minimally invasive endometrial biopsy technique in reducing delay in diagnosis and subsequent possible preservation of fertility.
Topics: Endometriosis; Endometrium; Female; Humans; Myometrium; Nerve Fibers; Pelvic Pain
PubMed: 19657753
DOI: 10.1080/00016340903176826 -
Women's Health (London, England) Aug 2015Several lines of recent evidence suggest that pelvic innervation is altered in endometriosis-affected women, and there is a strong presumption that nerve fibers... (Review)
Review
Several lines of recent evidence suggest that pelvic innervation is altered in endometriosis-affected women, and there is a strong presumption that nerve fibers demonstrated in eutopic endometrium (of women with endometriosis) and in endometriotic lesions play roles in the generation of chronic pelvic pain. The recent observation of sensory C, sensory A-delta, sympathetic and parasympathetic nerve fibers in the functional layer of endometrium of most women affected by endometriosis, but not demonstrated in most women who do not have endometriosis, was a surprise. Nerve fiber densities were also greatly increased in myometrium of women with endometriosis and in endometriotic lesions compared with normal peritoneum. Chronic pelvic pain is complex, and endometriosis is only one condition which contributes to this pain. The relationship between the presence of certain nerve fibers and the potential for local pain generation requires much future research. This paper reviews current knowledge concerning nerve fibers in endometrium, myometrium and endometriotic lesions, and discusses avenues of research that may improve our knowledge and lead to enriched understanding and management of endometriotic pain symptoms.
Topics: Adult; Endometriosis; Endometrium; Female; Humans; Myometrium; Nerve Fibers; Pelvic Pain; Women's Health
PubMed: 26314611
DOI: 10.2217/whe.15.47 -
ENeuro 2022To understand how vowels are encoded by auditory nerve (AN) fibers, a number of representation schemes have been suggested that extract the vowel's formant frequencies...
To understand how vowels are encoded by auditory nerve (AN) fibers, a number of representation schemes have been suggested that extract the vowel's formant frequencies from AN-fiber spiking patterns. The current study aims to apply and compare these schemes for AN-fiber responses to naturally-spoken vowels in a speech-shaped background noise. Responses to three vowels were evaluated; based on behavioral experiments in the same species, two of these were perceptually difficult to discriminate from each other (/e/ vs /i/), and one was perceptually easy to discriminate from the other two (/a:/). Single-unit AN fibers were recorded from ketamine/xylazine-anesthetized Mongolian gerbils of either sex ( = 8). First, single-unit discrimination between the three vowels was studied. Compared with the perceptually easy discriminations, the average spike timing-based discrimination values were significantly lower for the perceptually difficult vowel discrimination. This was not true for an average rate-based discrimination metric, the rate d-prime (d'). Consistently, spike timing-based representation schemes, plotting the temporal responses of all recorded units as a function of their best frequency (BF), i.e., dominant component schemes, average localized interval rate, and fluctuation profiles, revealed representation of the vowel's formant frequencies, whereas no such representation was apparent in the rate-based excitation pattern. Making use of perceptual discrimination data, this study reveals that discrimination difficulties of naturally-spoken vowels in speech-shaped noise originate peripherally and can be studied in the spike timing patterns of single AN fibers.
Topics: Auditory Perception; Cochlear Nerve; Nerve Fibers; Noise; Phonetics; Speech; Speech Perception
PubMed: 35086866
DOI: 10.1523/ENEURO.0474-21.2021