Clinical trials have demonstrated that kilohertz-frequency transcutaneous spinal cord stimulation (TSCS) can be used to facilitate the recovery of sensory-motor function for patients with spinal cord injury, whereas the neural mechanism of TSCS is still undetermined so that the choice of stimulation parameters is largely dependent on the clinical experience. In this paper, a finite element model of transcutaneous spinal cord stimulation was used to calculate the electric field distribution of human spinal cord segments T ₁₂ to L ₂, whereas the activation thresholds of spinal fibers were determined by using a double-cable neuron model. Then the variation of activation thresholds was obtained by varying the carrier waveform, the interphase delay, the modulating frequency, and the modulating pulse width. Compared with the sinusoidal carrier, the usage of square carrier could significantly reduce the activation threshold of dorsal root (DR) fibers. Moreover, the variation of activation thresholds was no more than 1 V due to the varied modulating frequency and decreases with the increased modulating pulse width. For a square carrier at 10 kHz modulated by rectangular pulse with the frequency of 50 Hz and the pulse width of 1 ms, the lowest activation thresholds of DR fibers and dorsal column fibers were 27.6 V and 55.8 V, respectively. An interphase delay of 5 μs was able to reduce the activation thresholds of the DR fibers to 20.1 V. The simulation results can lay a theoretical foundation on the selection of TSCS parameters in clinical trials.
Humans ; Spinal Cord Stimulation/methods* ; Nerve Fibers/physiology* ; Finite Element Analysis ; Spinal Cord/physiology* ; Computer Simulation ; Spinal Cord Injuries/physiopathology* ; Lumbosacral Region ; Lumbar Vertebrae ; Transcutaneous Electric Nerve Stimulation/methods* ; Models, Neurological

OBJECTIVE: To provide useful information for selecting the most appropriate peripheral nerve injury model for different research purposes in nerve injury and repair studies, and to compare nerve regeneration capacity and characteristics between them. METHODS: Sixty adult SD rats were randomly divided into two groups and underwent crush injury alone (group A, n = 30) or transection injury followed by surgical repair (group B, n = 30) of the right hind paw. Each group was subjected to the CatWalk test, gastrocnemius muscle evaluation, pain threshold measurement, electrophysiological examination, retrograde neuronal labeling, and quantification of nerve regeneration before and 7, 14, 21, and 28 days after injury. RESULTS: Gait analysis showed that the recovery speed in group A was significantly faster than that in group B at 14 days. At 21 days, the compound muscle action potential of the gastrocnemius muscle in group A was significantly higher than that in group B, and the number of labeled motor neurons in group B was lower than that in group A. The number of new myelin sheaths and the g-ratio were higher in group A than in group B. There was a 7-day time difference in the regeneration rate between the two injury groups. CONCLUSION The regeneration of nerve fibers was rapid after crush nerve injury, whereas the transection injury was relatively slow, which provides some ideas for the selection of clinical research models.
Animals ; Rats ; Nerve Fibers ; Nerve Regeneration ; Rats, Sprague-Dawley ; Sciatic Nerve/injuries*

BACKGROUND: Corneal confocal microscopy (CCM) is a noninvasive technique to detect early nerve damage of diabetic sensorimotor polyneuropathy (DSPN). Time in range (TIR) is an emerging metric of glycemic control which was reported to be associated with diabetic complications. We sought to explore the relationship between TIR and corneal nerve parameters in asymptomatic patients with type 2 diabetes (T2DM). METHODS: In this cross-sectional study, 206 asymptomatic inpatients with T2DM were recruited. After 7 days of continuous glucose monitoring, the TIR was calculated as the percentage of time in the glucose range of 3.9 to 10.0 mmol/L. CCM was performed to determine corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length (CNFL). Abnormal CNFL was defined as ≤15.30 mm/mm 2 . RESULTS: Abnormal CNFL was found in 30.6% (63/206) of asymptomatic subjects. Linear regression analyses revealed that TIR was positively correlated with CCM parameters both in the crude and adjusted models (all P   <  0.05). Each 10% increase in TIR was associated with a 28.2% (95% CI: 0.595-0.866, P  = 0.001) decreased risk of abnormal CNFL after adjusting for covariates. With the increase of TIR quartiles, corneal nerve fiber parameters increased significantly (all P for trend <0.01). The receiver operating characteristic curve indicated that the optimal cutoff point of TIR was 77.5% for predicting abnormal CNFL in asymptomatic patients. CONCLUSIONS There is a significant independent correlation between TIR and corneal nerve fiber loss in asymptomatic T2DM patients. TIR may be a useful surrogate marker for early diagnosis of DSPN.
Humans ; Diabetes Mellitus, Type 2/complications* ; Cross-Sectional Studies ; Blood Glucose Self-Monitoring ; Blood Glucose ; Nerve Fibers ; Diabetic Neuropathies ; Cornea ; Microscopy, Confocal/methods*

OBJECTIVE: To observe the effect of moxibustion at "Zusanli" (ST 36) on distal, middle and proximal colonic mucosal injury and expression of calcitonin gene-related peptide (CGRP) positive nerve fibers of distal colonic mucosa in ulcerative colitis (UC) mice at different time points. METHODS: A total of 51 C57BL/6N mice were randomized into a 7-day control group ( RESULTS: Mucosal injury can be observed in mice after modeling, displaying epithelial layer disappearance, abnormal crypt structure or crypt disappearance. Compared with the 7-day control group, colon length was shortened ( CONCLUSION Moxibustion at "Zusanli" (ST 36) can reduce the expressions of positive nerve fibers of colonic mucosa and CGRP positive nerve fibers of distal colonic mucosa, thus, improve the colonic mucosal injury.
Animals ; Calcitonin ; Calcitonin Gene-Related Peptide/genetics* ; Colitis, Ulcerative/therapy* ; Intestinal Mucosa ; Mice ; Mice, Inbred C57BL ; Moxibustion ; Nerve Fibers

Objective: To study the oropharyngeal sensory function by Current Perception Threshold(CPT) detection, to explore the detection method of oropharyngeal sensory function in normal population, and to analyze the possible influencing factors. Methods: Fifty-eight normal subjects were included prospectively in this study. Age, gender, body mass index (BMI) were collected. The age of the subjects ranged from 20 to 76 (43.27±13.52) years old. There were 34 females with 17 in childbearing period and 17 in menopause; and 24 males were included.In all the cases, 6 cases were in low BMI, 39 cases were in normal BMI, 10 cases were overweight and 3 cases were suffering from obesity. The CPT system of Neurometer was used to stimulate bilateral palatoglossal arch and tongue base.The current used was 2000 Hz, 250 Hz and 5 Hz respectively.The function of type Aβ, Aδ and C sensory nerve fibers were tested and the CPT values were recorded.The values were inversely proportional to pharyngeal sensation function.To evaluate the oropharyngeal sensory function of the subjects, the CPT values of each frequency at each testing point were compared. SPSS 25.0 software was used for statistical analysis. Results: The CPT value of palatoglossal arch was significantly lower than that of tongue base (t=-2.58,-2.65,-2.54,-2.47,-2.37,-2.77,P<0.05), 2 000 Hz>250 Hz>5 Hz, and there was no significant difference between left and right sides(t=-0.03,-0.51,-0.49,0.06,-0.16,0.13,P>0.05). The CPT value of male was slightly higher than that of female (t=0.92,1.55,0.27,0.78,1.44,1.26,0.35,0.77,1.27,0.24,0.78,0.96,P>0.05). The CPT values of women in childbearing period were significantly less than those in menopausal women (t=-3.90,-3.64,-2.14,-4.20,-4.28,-4.28,-3.52,-4.46,-3.41,-3.63,-4.66,-2.86,P<0.05). The CPT value increased with age, and the values of all frequency of 20 to 30 years old group was significantly lower than those of subjects over 40 years old at each point (The t values of bilateral palatoglossal arch at 2 000 Hz were -5.57,-6.22,-10.18,-11.00;the t values of bilateral palatoglossal arch at 250 Hz were -6.39,-8.79,-6.39,-15.61;the t values of bilateral palatoglossal arch at 5 Hz were -7.09, -5.57, -9.26, -15.23;the t values of tongue base at 2 000 Hz were -3.11,-3.88,-7.60,-8.55;the t values of tongue base at 250 Hz were -6.31,-10.59,-8.52,-10.60;the t values of tongue baseat 5 Hz were -6.69,-5.09,-8.70,-7.07,P<0.05).The values at all frequencies and testing points of 30-40 years old group were significantly lower than those of all subjects over 60 years old (The t values of bilateral palatoglossal arch at 2 000 Hz were -10.91,-12.42;the t values of bilateral palatoglossal arch at 250 Hz were -6.25,-10.87;the t values of bilateral palatoglossal arch at 5 Hz were -5.53,-11.01;the t values of tongue base at 2 000 Hz were -8.62,-10.12;the t values of tongue base at 250 Hz were -6.89,-7.82;the t values of tongue base at 5 Hz were -6.13,-6.48,P<0.05). Conclusions: CPT can be used to evaluate oropharyngeal sensory function. The sensitivity of tongue base is lower than that of palatoglossal arch, there is no significant difference in oropharyngeal sensory function between male and female,between left and right sides. There are many factors influencing oropharyngeal sensory function. Age, hormone level changes may affect the sensitivity of oropharyngeal sensory function.
Adult ; Aged ; Electric Stimulation ; Female ; Humans ; Male ; Middle Aged ; Nerve Fibers ; Pharynx ; Sensation ; Sensory Thresholds ; Young Adult

nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GCIPL).METHODS: One hundred sixty-four eyes with primary open-angle glaucoma were studied. The structural progression pattern evaluated by optical coherence tomography guided progression analysis was classified using hierarchical cluster analysis. The clinical parameters, patterns of structural progression, and visual field (VF) changes were compared among the groups.RESULTS: Three groups were included: stable, progressive peripapillary RNFL thinning without macular GCIPL involvement, and progressive thinning of both the peripapillary RNFL and macular GCIPL. The third group, those with progressive peripapillary RNFL and macular GCIPL thinning, showed more progressive peripapillary RNFL thinning in the inferotemporal area and VF progression in the parafoveal area. Conversely, the 12 and 6 o'clock areas were the most common locations of progressive peripapillary RNFL thinning in the group without macular GCIPL involvement.CONCLUSIONS: Structural progression patterns of glaucoma can be categorized into three groups. The location of progressive peripapillary RNFL thinning is associated with progressive macular GCIPL thinning and pattern of VF changes in the affected area. Our results indicate that the use of only macular GCIPL analysis is inadequate for analyzing the structural progression of glaucoma.]]>
Cluster Analysis ; Ganglion Cysts ; Glaucoma ; Glaucoma, Open-Angle ; Machine Learning ; Nerve Fibers ; Retinaldehyde ; Tomography, Optical Coherence ; Visual Fields

PURPOSE: To report a case of non-glaucomatous retinal nerve fiber layer (RNFL) defect associated with paravascular inner retinal defect (PIRD) in a patient with idiopathic epiretinal membrane (ERM).CASE SUMMARY: A 70-year-old male who was diagnosed with ERM in his right eye and pseudoexfoliative glaucoma in his left eye visited our clinic. His intraocular pressure was 14 mmHg in both eyes while using topical hypotensive medications in both eyes. His right eye showed no glaucomatous change of the optic disc head, and also no glaucomatous visual field defect on standard automated perimetry. Red-free fundus photography and swept-source optical coherence tomography showed an ERM and wedge-shaped RNFL defect starting from the PIRD, not the optic disc head. He was diagnosed with non-glaucomatous RNFL defect in the right eye and was told to stop using topical hypotensive medication for the right eye. After 2 years of discontinuing the medication, the IOP was within the normal range, the RNFL defect showed no progression, and the visual field remained stationary.CONCLUSIONS: A non-glaucomatous RNFL defect can develop in association with PIRD in patients with idiopathic ERM. Examinations for PIRD as well as evaluation of the optic disc head are therefore necessary in patients with ERM and RNFL defect.
Aged ; Epiretinal Membrane ; Glaucoma ; Head ; Humans ; Intraocular Pressure ; Male ; Nerve Fibers ; Photography ; Reference Values ; Retinaldehyde ; Tomography, Optical Coherence ; Visual Field Tests ; Visual Fields

BACKGROUND AND PURPOSE: Cutaneous nerve biopsies based on two-dimensional analysis have been regarded as a creditable assessment tool for diagnosing peripheral neuropathies. However, advancements in methodological imaging are required for the analysis of intact structures of peripheral nerve fibers. A tissue-clearing and labeling technique facilitates three-dimensional imaging of internal structures in unsectioned, whole biological tissues without excessive time or labor costs. We sought to establish whether a tissue-clearing and labeling technique could be used for the diagnostic evaluation of peripheral neuropathies. METHODS: Five healthy individuals and four patients with small-fiber neuropathy (SFN) and postherpetic neuralgia (PHN) were prospectively enrolled. The conventional methods of indirect immunofluorescence (IF) and bright-field immunohistochemistry (IHC) were adopted in addition to the tissue-clearing and labeling method called active clarity technique-pressure related efficient and stable transfer of macromolecules into organs (ACT-PRESTO) to quantify the intraepidermal nerve-fiber density (IENFD). RESULTS: The mean IENFD values obtained by IF, bright-field IHC, and ACT-PRESTO in the healthy control group were 6.54, 6.44, and 90.19 fibers/mm², respectively; the corresponding values in the patients with SFN were 1.99, 2.32, and 48.12 fibers/mm², respectively, and 3.06, 2.87, and 47.21 fibers/mm², respectively, in the patients with PHN. CONCLUSIONS: This study has shown that a tissue-clearing method provided not only rapid and highly reproducible three-dimensional images of cutaneous nerve fibers but also yielded reliable quantitative IENFD data. Quantification of the IENFD using a tissue-clearing and labeling technique is a promising way to improve conventional cutaneous nerve biopsies.
Biopsy ; Fluorescent Antibody Technique, Indirect ; Humans ; Imaging, Three-Dimensional ; Immunohistochemistry ; Methods ; Nerve Fibers ; Neuralgia, Postherpetic ; Peripheral Nerves ; Peripheral Nervous System Diseases ; Prospective Studies

BACKGROUND AND PURPOSE: Diagnosing small-fiber neuropathy (SFN) is challenging because there is no gold-standard test and few diagnostic tests. This study investigated the clinical symptom profile and its associations with the results of quantitative sensory testing (QST) and the quantitative sudomotor axon reflex test (QSART) as well as the quality of life (QOL) in patients with clinically suspected SFN. METHODS: This study involved 63 patients with clinically suspected length-dependent SFN. Assessments were performed using QST, QSART, SFN Symptoms Inventory Questionnaire, Neuropathic Pain Symptom Inventory, ‘Sirim’ frequency and ‘Sirim’ (cold) pain severity, and 36-item Short-Form Health Survey. Multiple logistic and linear regression analyses were performed to predict risk factors for QST or QSART abnormalities and QOL, respectively. RESULTS: ‘Sirim’ and ‘Sirim’ pain was the most-common (84%) and the most-severe complaint (mean score of 6.3 on a numerical rating scale ranging from 0 to 10) in patients with clinically suspected SFN. The findings of QST [cold detection threshold (CDT)] and QSART were abnormal in 71% (n=45/57) and 62% (n=39/56) of the patients, respectively. An abnormal CDT was correlated with more-severe stabbing pain (odds ratio=2.23, 95% CI=1.02–4.87, p=0.045). Restless-leg symptoms (β=−7.077) and pressure-evoked pain (β=−5.034) were independent predictors of the physical aspects of QOL. CONCLUSIONS: ‘Sirim’ pain, similar to cold pain, should be considered a major neuropathic pain in SFN. Among pain characteristics, stabbing pain of a spontaneous paroxysmal nature may be more pronounced in the setting of dysfunctional Aδ fibers with functional autonomic C fibers.
Axons ; Diagnostic Tests, Routine ; Erythromelalgia ; Health Surveys ; Humans ; Linear Models ; Nerve Fibers, Unmyelinated ; Neuralgia ; Quality of Life ; Reflex ; Risk Factors

BACKGROUND/AIMS: Functional dyspepsia (FD) is characterized as chronic recurrent upper gastrointestinal symptoms in the absence of any organic disorder. We hypothesized that duodenal low-grade inflammation activates superficial afferent nerve sprouting, thereby contributing to hypersensitivity in patients with FD. METHODS: A prospective case-control study was conducted in a tertiary referral center. FD was defined using the Rome III criteria. Standardized endoscopic biopsies were performed in the stomach and duodenum. Hematoxylin and eosin staining and immunohistochemical staining for major basic proteins were performed to detect granulated eosinophil-derived granules, and S-100 staining was performed to detect fine nerve fibers. RESULTS: A total of 51 patients with FD (82% female; mean age 35.8 ± 13.4 years) and 35 controls were enrolled. Activated eosinophil counts in the duodenum were significantly higher in patients with FD than in controls (41.4% vs 17.1%, P = 0.005). Microscopic duodenitis was more frequently detected in patients with FD than in controls. Fine nerve fibers were more abundant in patients with FD than in controls (45.1% vs 11.4%, P = 0.029). The abundance of fine nerve fibers highly correlated with the degree of activated eosinophils. CONCLUSION: Duodenal low-grade inflammation, such as mucosal eosinophilic accumulation with degranulation, promoted mucosal enteric nerve fiber density and sprouting in patients with FD.
Biopsy ; Case-Control Studies ; Duodenitis ; Duodenum ; Dyspepsia ; Eosine Yellowish-(YS) ; Eosinophils ; Female ; Hematoxylin ; Humans ; Hypersensitivity ; Inflammation ; Mucous Membrane ; Nerve Fibers ; Peripheral Nervous System ; Prospective Studies ; Stomach ; Tertiary Care Centers