Unmyelinated Nerve Fibers Research Articles

Transarterial Embolization for Musculoskeletal Pain Management: AJR Expert Panel Narrative Review.

Musculoskeletal embolization has emerged in recent years as a treatment for chronic joint pain, as the inflammatory cascade responsible for such pain has become better understood. Studies have demonstrated a complex interplay between joint inflammation and synovial hypervascularity that causes growth of new unmyelinated nerve fibers responsible for pain. Embolization targets joint hypervascularity, to disrupt the inflammatory cycle and provide pain relief. The standard treatment algorithm for chronic joint pain is well-established and entails escalating therapeutic options that include exercise, self-management programs, analgesic medications, intra-articular injections, and finally surgical replacement or release. Genicular artery embolization (GAE), targeting abnormal vasculature around the knee joint, is the most heavily studied musucloskeletal embolization procedure, reflecting the high worldwide prevalence and increasing incidence of knee osteoarthritis. GAE is now supported by multiple prospective studies, including randomized control trials comparing GAE versus sham treatment. Embolization has also extended outside of the knee joint to include the shoulder (treatment of adhesive capsulitis or secondary stiff shoulder), elbow (medial/lateral epicondylitis), hip (osteoarthritis, great trochanteric pain syndrome), and ankle (plantar fasciitis). This AJR Expert Panel Narrative Review discusses the current status of transarterial embolization for musculoskeletal pain management, focusing on treatment of knee osteoarthritis and chronic shoulder pain.

Maternal exposure to low-dose bisphenol A and its potential neurotoxic impact on male pups: A histological, immunohistochemical, and ultrastructural study

BackgroundBisphenol A (BPA) is a widely used chemical with a harmful effect on animal and human. The neonatal and juvenile period is a highly risky neurodevelopmental period. AimThis study aimed to determine how male albino rat pups’ cerebral cortex was altered by low doses of BPA given to mothers and the role of the oxidative stress. MethodsThirty pregnant rats were randomly split into three equal groups, negative control, and positive control: received 1 cc of corn oil once a day through gastric tube and BPA treated: a dose of 200 µg/kg/day (dissolved in 1 cc corn oil). The male rat pups of each group were sacrificed at 1 week, 3 weeks and 6 weeks. The cerebra were then separated from the brain for histological and biochemical studies. ResultsRats administered BPA had raised levels of lipid peroxidation marker (MDA), lower levels of enzymatic antioxidants (SOD and CAT) with decreased body, cerebral weights, and decreased levels of non-enzymatic antioxidant defense (GSH). Histo-pathologically, shrunken pyramidal cells with congested blood vessels appeared. GFAP displayed increased number of positive immune-reactive astrocytes with high statistically significant increase in the area % in BPA treated group when compared to the control groups, on contrary to MBP. Semi-thin and ultra-thin BPA-sections revealed degenerative changes in myelinated axons with tiny nucleus and broken nuclear membranes. Lysosomes, dilated endoplasmic reticulum cisternae with noticeable increase in unmyelinated nerve fibers were also observed. ConclusionThe structure of the developing cerebral cortex is negatively impacted by BPA due to oxidative stress.

Neuro-microcirculatory interrelationships in patients with kyphoscoliosis associated with neurological deficits

Background: The use of laser Doppler flowmetry with spectral wavelet analysis of blood flow fluctuations allows us to assess the functional state of thin unmyelinated nerve fibers and objectify the dynamics of recovery processes in patients with kyphoscoliotic spinal deformities associated with spinal cord compression. AIM: To study the features of neuromicrocirculatory relationships in patients with kyphoscoliosis associated with neurological deficits before and after surgical treatment. MATERIALS AND METHODS: 20 patients with spinal deformities associated with neurological deficits of varying severity were examined using the LDF method and operated on. Patients were examined before surgery, 1–2 weeks after surgery following regression of acute postoperative pain syndrome, 3–6 months, 6–12 months, and more than a year after surgery. The scope of the study included a general examination with a detailed assessment of the neurological status, radiation diagnostics (postural radiographs of the spine, computed tomography and magnetic resonance imaging of the spine with assessment of spinal canal stenosis). Patients with severe kyphoscoliotic deformities underwent CT myelography followed by the design of individual full-size 3D plastic models of the spine and myeloradicular structures. LDF with wavelet analysis was carried out at all periods of the survey. A perfusion study with determination of the average microcirculation was carried out at the level of the pad of the distal phalanx of the big toe using a two-channel LAKK-02 device with a semiconductor laser (sensing in the red Raman and infrared IR channels). The obtained LDF results were processed by spectral amplitude-frequency wavelet analysis to characterize microcirculation regulation factors in the ranges of sympathetic adrenergic regulation (0.02–0.046 Hz), sensory peptidergic influences (0.047–0.069 Hz), myogenic oscillations (0.07–0.145 Hz). RESULTS: After surgery, the activity of trophotropic sensory peptidergic nerve fibers, the values of perfusion of the microcirculatory channel increased and was maintained starting from the early postoperative period. Ergotropic sympathetic adrenergic activity was significantly decreased in the period of 6-12 months after surgery. Maximum mobilization of trophotropic neurogenic mechanisms of sanogenesis was observed in the period of 6-12 months after surgery. CONCLUSION: The obtained data indicate a significant participation of thin nerve fibers in the recovery processes after decompressive surgeries in the spinal canal zone and the creation of anatomical conditions for neurophysiological repair at the spinal cord level. The use of the LDF method with spectral wavelet analysis of blood flow fluctuations makes it possible to objectify the dynamics of thin unmyelinated nerve fibers and recovery processes in patients with kyphoscoliotic deformities of the spine associated with spinal cord compression.

Selective intrafascicular stimulation of myelinated and unmyelinated nerve fibers through a longitudinal electrode: A computational study

Carbon nanotube (CNT) fiber electrodes have demonstrated exceptional spatial selectivity and sustained reliability in the context of intrafascicular electrical stimulation, as evidenced through rigorous animal experimentation. A significant presence of unmyelinated C fibers, known to induce uncomfortable somatosensory experiences, exists within peripheral nerves. This presence poses a considerable challenge to the excitation of myelinated Aβ fibers, which are crucial for tactile sensation. To achieve nuanced tactile sensory feedback utilizing CNT fiber electrodes, the selective stimulation of Aβ sensory afferents emerges as a critical factor.In confronting this challenge, the present investigation sought to refine and apply a rat sciatic-nerve model leveraging the capabilities of the COMSOL-NEURON framework. This approach enables a systematic evaluation of the influence exerted by stimulation parameters and electrode geometry on the activation dynamics of both myelinated Aβ and unmyelinated C fibers. The findings advocate for the utilization of current pulses featuring a pulse width of 600 μs, alongside the deployment of CNT fibers characterized by a diminutive diameter of 10 μm, with an exclusively exposed cross-sectional area, to facilitate reduced activation current thresholds. Comparative analysis under monopolar and bipolar electrical stimulation conditions revealed proximate activation thresholds, albeit with bipolar stimulation exhibiting superior fiber selectivity relative to its monopolar counterpart. Concerning pulse waveform characteristics, the adoption of an anodic-first biphasic stimulation modality is favored, taking into account the dual criteria of activation threshold and fiber selectivity optimization. Consequently, this investigation furnishes an efficacious stimulation paradigm for the selective activation of touch-related nerve fibers, alongside provisioning a comprehensive theoretical foundation for the realization of natural tactile feedback within the domain of prosthetic hand applications.

Cutaneous nerve biopsy in patients with symptoms of small fiber neuropathy: a retrospective study.

We aimed to investigate to what extent small fiber tests were abnormal in an unselected retrospective patient material with symptoms suggesting that small fiber neuropathy (SFN) could be present, and to evaluate possible gender differences. Nerve conduction studies (NCS), skin biopsy for determination of intraepidermal nerve fiber density (IENFD) and quantitative sensory testing (QST) were performed. Z-scores were calculated from reference materials to adjust for the effects of age and gender/height. Two hundred and three patients, 148 females and 55 males had normal NCS and were considered to have possible SFN. 45.3 % had reduced IENFD, 43.2 % of the females and 50.9 % of the males. Mean IENFD was 7.3±2.6 fibers/mm in females and 6.1±2.3 in males (p<0.001), but the difference was not significant when adopting Z-scores. Comparison of gender differences between those with normal and abnormal IENFD were not significant when Z-scores were applied. QST was abnormal in 50 % of the patients (48.9 % in females and 52.9 % in males). In the low IENFD group 45 cases out of 90 (50 %) were recorded with abnormal QST. In those with normal IENFD 51 of 102 (50 %) showed abnormal QST. Less than half of these patients had reduced IENFD, and 50 % had abnormal QST. There were no gender differences. A more strict selection of patients might have increased the sensitivity, but functional changes in unmyelinated nerve fibers are also known to occur with normal IENFD. Approval to collect data was given by the Norwegian data protection authority at University Hospital of North Norway (Project no. 02028).

A Combination Effect of Sensory Motor Training and Proprioceptive Neuromuscular Facilitation in a Case of Peripheral Polyneuropathy Manifested by Foot Drop in Type II Diabetes Mellitus – A Case Study

Peripheral neuropathy is one of the common complications in patients with diabetes Mellitus (DM) which leads to disrupting the peripheral nervous system resulting in reduce sensory inputs and motor outputs. Patients with foot drop (FD) will have weakness in dorsiflexor muscles of ankle and toe and sensory loss due to disruption of small myelinated and unmyelinated nerve fibers. Sensory motor training (SMT) will facilitate sensory inputs, correcting muscle imbalance, and ensuring correct program at the level of central nervous system whereas Proprioceptive Neuromuscular facilitation techniques (PNF) not only helps facilitating the weaker group of muscles also improve strength . Hence the purpose of the study to combine the effect on use of SMT along with PNF in a case of peripheral polyneuropathy manifested by foot drop in patient with type II DM. The case report study of 72 year old male patient diagnosed with diabetic polyneuropathy manifested by foot drop in type II diabetes mellitus on medication. Intervention of patient received Sensory motor training and Proprioceptive Neuromuscular Facilitation in foot drop for 5 days a week for 4 weeks and outcome measures used were Stanmore Assessment Questionnaire (SAQ) , Diabetic Neuropathy Examination (DNE) score for diabetic neuropathy which were taken on day one and after 4 weeks of intervention and results shown improved on both the outcome measures which concluded that on combination of SMT and PNF techniques have shown efficacy on improving ankle range of motion and strength , sensory discrimination , thereby implementing these combination techniques, will reduce functional dependence and improve quality of life.

Validated computational models predict vagus nerve stimulation thresholds in preclinical animals and humans

Objective. We demonstrated how automated simulations to characterize electrical nerve thresholds, a recently published open-source software for modeling stimulation of peripheral nerves, can be applied to simulate accurately nerve responses to electrical stimulation. Approach. We simulated vagus nerve stimulation (VNS) for humans, pigs, and rats. We informed our models using histology from sample-specific or representative nerves, device design features (i.e. cuff, waveform), published material and tissue conductivities, and realistic fiber models. Main results. Despite large differences in nerve size, cuff geometry, and stimulation waveform, the models predicted accurate activation thresholds across species and myelinated fiber types. However, our C fiber model thresholds overestimated thresholds across pulse widths, suggesting that improved models of unmyelinated nerve fibers are needed. Our models of human VNS yielded accurate thresholds to activate laryngeal motor fibers and captured the inter-individual variability for both acute and chronic implants. For B fibers, our small-diameter fiber model underestimated threshold and saturation for pulse widths >0.25 ms. Our models of pig VNS consistently captured the range of in vivo thresholds across all measured nerve and physiological responses (i.e. heart rate, Aδ/B fibers, Aγ fibers, electromyography, and Aα fibers). In rats, our smallest diameter myelinated fibers accurately predicted fast fiber thresholds across short and intermediate pulse widths; slow unmyelinated fiber thresholds overestimated thresholds across shorter pulse widths, but there was overlap for pulse widths >0.3 ms. Significance. We elevated standards for models of peripheral nerve stimulation in populations of models across species, which enabled us to model accurately nerve responses, demonstrate that individual-specific differences in nerve morphology produce variability in neural and physiological responses, and predict mechanisms of VNS therapeutic and side effects.

Fiber counts and architecture of the human dorsal penile nerve

The human penis transmits behaviorally important sensory information via the dorsal penile nerve, which is required for initiation and maintenance of erection. The human penis differs from the penes of other hominids. The lack of a baculum makes the human penis dependent on erectile tissue, which is under control of neural signals activated by tactile stimulation. Accordingly, the penile sensory innervation is crucial for human sexual behavior. To clarify penile innervation, we analyzed the architecture of the dorsal penile nerve of five male subjects who donated their body. We stained the sensory fibers in the penile dorsal nerve with anti-neurofilament H antibody, and identified myelinated axons with Luxol fast blue staining. Furthermore, we visualized nerve bundles as they travel along the shaft of the penis by performing microfocus computed tomography scans after counterstaining penes with iodine. Our results show that the dorsal penile nerve is organized in 25–45 loosely packed nerve bundles, running mediodorsally in the shaft of the penis. This organization corresponds to that in penes of other mammalian species, but differs from the organization of the other peripheral sensory nerves. Around half of the dorsal penile nerve fibers were myelinated and a human hemipenis contained a total of 8290 ± 2553 (mean ± SD) axons. Thus, the number of sensory axons in the human dorsal penile nerve is higher than in other species described so far. The large fraction of unmyelinated nerve fibers suggests that the conduction speed is not a crucial aspect of penile sensory transmission.

Fibromyalgia syndrome and the eye-Implications in corneal ultrastructure on confocal microscopy.

Fibromyalgia is a chronic systemic disorder associated with varied manifestations ranging from fatigue, sleep disturbances, headaches, muscular pain, cognitive issues, or even without symptoms. It is also known to be associated with chronic neuropathic pain.[1,2] Ocular features described include severe pain, necrotizing scleritis, and changes in optic disc perfusion.[3] Small fiber neuropathy and dysautonomia symptoms correlate with corneal denervation more commonly in women with fibromyalgia. These nerve plexus features were found to be associated with neuropathic pain and fibromyalgia in previous studies.[4] These patients have a higher incidence of dry eye disease as compared to the normal population.[5,6] Approximately 50% of patients with fibromyalgia have damage to small unmyelinated nerve fibers around the body.[7] Small fiber polyneuropathy may cause symptoms sometimes identified as fibromyalgia.[8] A skin punch biopsy is a sensitive and specific test that demonstrates the reduction in nerve fiber density associated with small fiber neuropathy. In vivo confocal microscopy (IVCM) is a noninvasive tool that can demonstrate nerve-related changes in the cornea and hence serve as an adjunct to skin biopsy for diagnosis and evaluation of the disease.[9] This photoessay highlights the nerve-related changes and the presence of microneuromas in the cornea and the use of IVCM in aiding in the diagnosis and management of these patients. Case Reports Three patients previously diagnosed with fibromyalgia presented with ocular pain and mild mixed dry eye. IVCM showed decreased corneal nerve fiber branching density with microneuromas in the cornea [Fig. 1]. They were on systemic therapy for chronic pain and their ocular condition was managed with topical anti-inflammatory and lubricating eye drops. These patients can be at a risk for postoperative dry eye and wound-healing complications and should be evaluated in detail preoperatively to avoid this.Figure 1: (a, b, and c) show microneuromas in the subbasal nerve plexus on IVCM of all three patients with fibromyalgia and dry eye. Figure d shows reduced nerve density, e shows altered nerve morphology and f shows the image used for the calculation of nerve density using the CCMetrics softwareFinancial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Морфофункциональное состояние эндотелия сосудов в периферических нервах овец при патологии

In a comparative aspect, studies of experimental models of hepatosis in sheep, depending on etiological factors, were carried out. Comprehensive studies made it possible to characterize the morphofunctional state of the peripheral nervous system in sheep and the vascular endothelium. With prolonged exposure to various damaging factors, there is a gradual depletion of compensatory capabilities in the peripheral nervous system and the endothelial cover of the vessels, which leads to an increase in exudative activity, respectively, and vasoconstriction. the relaxing and constrictor functions of the endothelium are disturbed, as well as the production of anticoagulant and procoagulant substances, growth factors and their inhibitors, etc. It has been established that due to the commonality of innervation, blood circulation of the abdominal organs in pathology, a combined pathology develops, which is manifested by the corresponding syndromes. In this regard, pathogenetic mechanisms of dysfunction of myelinated and unmyelinated nerve fibers and vascular endothelium have been established. Endothelial dysfunction occurs with an imbalance in the synthesis of endothelins, bradykinin, eicosanoids, NO, inactivation of acetylcholine, catecholamines, serotonin, histamine, etc. The vascular intima ceases to perform barrier, secretory, hemostatic, vasotonic functions, reducing its role in the processes of inflammation and remodeling of the vascular wall. Trophic function disorders are manifested by morphological changes in the peripheral nervous system. In myelinated and unmyelinated nerve fibers, dystrophic processes are induced that do not bypass neurolemmocytes and connective tissue.

Cytodifferentiation of Wulzen's cone of mature male sheep hypophysis cerebri with special emphasis on its parenchymal correlations with the adjacent pars distalis, pars intermedia and pars nervosa.

Hypophysis cerebri is considered the master endocrine gland as it plays a critical role in influencing and controlling the vitality of other endocrine organs via several hormones secretion. The present study was performed to clarify the localization of Wulzen's cone (WC) within sheep hypophysis and cytodifferentiation of the glandular cells filling cone parenchyma with particular emphasis on the cone correlations with adjacent pars distalis (pd), pars intermedia (pi), and pars nervosa (pn). Pituitaries were collected and processed histologically, then subjected to different combinations of special stains; Br-AB- OFG., PFA-AB-PAS-OG., PAS-Orange G., Orange G- Acid Fuchsin- Light Green, Bielschowsky technique, Masson's trichrome & Gomori's reticulin. A sagittal section through the pituitaries revealed a well-developed cone of glandular cells protruding from the pi like a tongue plate towards the hypophyseal cleft in the neighborhood of the pd and behind the pn. Resembling the pd, various glandular cells were distinguished in the cone; chromophobes and chromophils of acidophils & basophils. The cone is mainly formed from acidophils intermingled with the chromophobes. Meanwhile, basophils were primarily localized at the most anterior & posterior parts of the cone. In front of the cone, pd were localized, resembling a wing-shaped and filled with several categorized glandular cells; chromophobes and chromophils. Upper to the cone, pi were localized and composed mainly of weakly basophilic cuboidal or polygonal cells arranged in parallel cords or follicles. Behind the cone, pn was localized as a ventral outpouching of the brain floor-like water drop. Unlike the cone, it was devoid of any glandular secretory cells or nerve cells but consisted mainly of unmyelinated nerve fibers, herring bodies, and pituicytes. WC is present and well-developed in sheep adenohypophysis. Various glandular cells were distinguished, filling the cone, chromophobes, and chromophils of acidophils & basophils that were typically similar to the glandular cells of pd but with different distributions.

Confocal microscopy of the corneal nerve fibers

This article presents the results of confocal microscopy of the corneal nerve fibers (CNF). The transparency of the cornea provides a unique potential for in vivo visualization of thin unmyelinated nerve fibers at the level close to morphological study. Modern software eliminates the need for manual tracing of the confocal image fragments, allows objectifying the process of assessment of CNF structure based on quantitative indicators characterizing the length, density and tortuosity of the main nerve trunks. Clinical application of structural analysis of the CNF has two potential directions associated with immediate tasks of ophthalmology, as well as with interdisciplinary affairs. In terms of ophthalmology, this primarily concerns various surgical interventions potentially affecting the state of the cornea, and chronic pathological processes in the cornea of different nature. Such studies could analyze the degree of changes in the CNF, or the particularities of corneal reinnervation. The potential for interdisciplinary studies lies in using CNF as biomarkers of systemic polyneuropathies. Relative simplicity, high level of direct visualization of the thin nerve fibers, and the obtained results allow recommending corneal confocal microscopy as a tool for primary screening and consequent monitoring of neuropathies in addition to the conventional methods.

Dynamic touch induces autonomic changes in preterm infants as measured by changes in heart rate variability

Preterm birth significantly increases the risk of developing various long-term health problems and developmental disabilities. While touch is a crucial component of many perinatal care strategies, the neurobiological underpinnings are rarely considered. C-tactile fibers (CTs) are unmyelinated nerve fibers that are activated by low-force, dynamic touch. Touch directed specifically at CTs activates the posterior insular cortex, consistent with an interoceptive function, and has been shown to reduce heart rate and increase oxygen saturation. The current research compared the effect of five minutes of CT optimal velocity stroking touch versus five minutes of static touch on autonomic markers of preterm infants between 28 and 37 weeks gestational age. CT touch induces a higher increase in heart rate variability metrics related to the parasympathetic system, which persisted for a 5-minute post-touch period. Conversely, there was no such increase in infants receiving static touch. The present findings confirmed that CTs signal the affective quality of nurturing touch, thereby arguing an additional neurobiological substrate for the evident valuable impacts of neonatal tactile interventions and improving the effectiveness of such interventions.

Unravelling the role of unmyelinated nerve fibres in trigeminal neuralgia with concomitant continuous pain

ObjectiveIn this clinical and neurophysiological study, we aimed to test trigeminal nerve fibre function in patients with trigeminal neuralgia, with and without concomitant continuous pain. MethodsWe enrolled 65 patients with a definite diagnosis of primary trigeminal neuralgia. Patients were grouped according to whether they experienced purely paroxysmal pain (36) or also had concomitant continuous pain (29). All participants underwent trigeminal reflex testing to assess the function of large non-nociceptive myelinated fibres and laser-evoked potentials to assess the function of small myelinated Aδ and unmyelinated C fibres. Neurophysiological examiners were blinded to the affected side. ResultsThe only neurophysiological abnormality distinguishing the two groups of patients was the side asymmetry of C fibre-related laser-evoked potential amplitude (p = 0.005), which was higher in patients with concomitant continuous pain than in patients with purely paroxysmal pain (indicative of a reduced C fibre-related laser-evoked potential amplitude in the affected side of patients with concomitant continuous pain). ConclusionsOur clinical and neurophysiological study indicates that in patients with trigeminal neuralgia concomitant continuous pain is associated with unmyelinated C fibre damage as assessed with laser-evoked potentials. SignificanceOur findings suggest that concomitant continuous pain is related to unmyelinated C fibre loss, possibly triggering abnormal activity in denervated trigeminal second-order neurons.

The effect of pulsed radiofrequency application on nerve healing after sciatic nerve anastomosis in rats

ABSTRACT The Effect of Pulsed Radiofrequency Application on Nerve Healing After Sciatic Nerve Anastomosis in Rats. In this study, we aimed to evaluate the histomorphological and functional effect of Pulsed Radiofrequency (PRF) application on regeneration after experimental nerve damage in rats. Forty Sprague-Dawley male rats were used in the study. Sciatic nerve incision was applied to all rats and then anastomosis was performed. Twenty rats were separated as the control group, and the remaining 20 rats underwent PRF every day at 42oC, for 120 seconds. The groups were divided into two further subgroups to be sacrificed on the 15th and 30th days. Tissue samples were obtained from all groups at 24 hours and 72 hours after the injury. Sections of sciatic nerve samples were stained with hematoxylin-eosin for light microscopic investigation and prepared for evaluation of ultrastructural changes with transmission electron microscopy. In the evaluation of axon numbers and diameters were seen that the 30th-day RF group had an increase compared to the control group. In the electron microscopic examination, it was observed that myelinated and unmyelinated nerve fiber sheaths had borders that are more regular in the RF group, the nucleus structures of schwann cells were better preserved, mitochondrial damage was less, and the extensions of fibroblast and collagen fibers were smoother than the control group. The findings suggested that PRF application has a positive contribution histologically on nerve healing in the early period after full-layer incision nerve injury anastomosis surgery.

Molecular Mechanisms Underlying the Pain-Relieving Effects of Extracorporeal Shock Wave Therapy: A Focus on Fascia Nociceptors.

In recent years, extracorporeal shock wave therapy (ESWT) has received increasing attention for its potential beneficial effects on various bone and soft-tissue pathologies, yielding promising outcomes for pain relief and functional recovery. In fact, ESWT has emerged as an alternative, non-invasive, and safe treatment for the management of numerous musculoskeletal disorders, including myofascial pain syndrome (MPS). In particular, MPS is a common chronic painful condition, accounting for the largest proportion of patients affected by musculoskeletal problems. Remarkably, sensory innervation and nociceptors of the fascial system are emerging to play a pivotal role as pain generators in MPS. At the same time, increasing evidence demonstrates that application of ESWT results in selective loss of sensory unmyelinated nerve fibers, thereby inducing long-lasting analgesia. The findings discussed in the present review are supposed to add novel viewpoints that may further enrich our knowledge on the complex interactions occurring between disorders of the deep fascia including changes in innervation, sensitization of fascial nociceptors, the pathophysiology of chronic musculoskeletal pain of MPS, and EWST-induced analgesia. Moreover, gaining mechanistic insights into the molecular mechanisms of pain-alleviating effects of ESWT may broaden the fields of shock waves clinical practice far beyond the musculoskeletal system or its original application for lithotripsy.

Three-dimensional bioprinting sodium alginate/gelatin scaffold combined with neural stem cells and oligodendrocytes markedly promoting nerve regeneration after spinal cord injury.

Accumulating research has indicated that the transplantation of combined stem cells and scaffolds is an effective method for spinal cord injury (SCI). The development of three-dimensional (3D) bioprinting technology can make the 3D scaffolds combined with cells more accurate and effective for SCI treatment. However, unmyelinated newborn nerve fibers have no nerve signaling conduction, hampering recovery of motor function. In this study, we designed and printed a type of sodium alginate/gelatin scaffold loaded with neural stem cells and oligodendrocytes, which were involved in the formation of the myelin sheaths of neural cell axons. In order to observe the effectiveness of this 3D bioprinting scaffold, we transplanted it into the completely transected rat spinal cord, and then immunofluorescence staining, hematoxylin–eosin staining and behavioral assessment were performed. The results showed that this 3D bioprinting scaffold markedly improved the hindlimb motor function and promoted nerve regeneration. These findings suggested that this novel 3D bioprinting scaffold was a good carrier for cells transplantation, thereby enhancing spinal cord repair following injury.

The ultrastructural study of human cochlear nerve at different ages

Ultrastructural and molecular changes in the myelin of the cochlear nerve (CN) have been associated with decreased hearing-acuity with increasing age. But most of these are animal studies or with very few human samples. Hence, we studied the ultrastructure of the human CN at different ages.We obtained samples of CN from persons, who at the time of death belonged to young, middle or old age-groups; defined as ≤ 30, 31 to 50, and ≥ 51 years of age, respectively. These were processed for viewing under a transmission electron microscope (TEM). Morphology and morphometry were assessed after blinding the observer. Measurements of diameter (whole nerve fibre, axon), myelin thickness and calculation of G-ratio were made on calibrated images using ImageJ software. K-Means cluster analysis was performed based on total and inner nerve fibre area.Middle and old age CN showed degenerating axons, splitting of myelin sheath and myelin balloons. Between the middle and old age groups there was significant decrease in axon diameter (p<0.001), inner nerve fibre area (p<0.001), myelin thickness (p<0.001), nerve fibre diameter (p<0.001), and G-ratio (p<0.001). By clustering, we identified three distinct populations of myelinated nerve fibres: large, medium and small. The large fibres (by size), seen in the young, disappeared in the old age-group. We were unable to find any unmyelinated nerve fibres in this study.The morphological deterioration CN fibres may be a visible sign of molecular degeneration and contribute to decreased hearing-acuity.

Autonomic and Somatic Nerve Functions in Type 2 Diabetes Mellitus Patients: Electrophysiological Aspects.

Objectives: To investigate the relationship between neurophysiological sensory and motor nerve function parameters, assessed by nerve conduction studies (NCS) with parasympathetic autonomic function and by heart rate variability (HRV) tests in patients with type 2 diabetes mellitus (T2DM). Material and Methods: A total of 161 T2DM patients underwent NCS. Cardiac autonomic response was assessed by HRV tests to deep breathing (HRV DB), to Valsalva manoeuvre, and during postural change from lying to standing. Results: The amplitude of motor response in the median nerve, tibial nerve, and peroneal nerve was associated with reduced HRV DB (p = 0.0001). The amplitude of motor response in the median nerve, tibial nerve, and peroneal nerve was associated with reduced HRV Valsalva (p = 0.0001). The correlation between the amplitude of response in all sensory nerves (sural, median, and ulnar) and HRV DB was statistically significant (p = 0.0001). Conclusion: The results indicate that there is a correlation in T2DM patients between the damage of small myelinated and unmyelinated nerve fibres from cardiac autonomic nerves, assessed by HRV tests and damage of large motor and sensory fibres, assessed by NCS. Based on the above results, a combination of NCS and HRV tests should be considered in the neurophysiological approach to diabetic neuropathy.

Strength exercise for balance and gait in HIV-associated distal symmetrical polyneuropathy: A randomised controlled trial.

BackgroundHIV-associated peripheral neuropathy (PN) is a common neurological complication associated with HIV infection. Distal symmetrical polyneuropathy (DSPN) is the most commonly occurring type, which is associated with symptoms such as numbness, unsteady gait and, in some cases, muscle atrophy and weakness when myelinated nerve fibres are affected. If unmyelinated nerve fibres are affected, a painful neuropathy and autonomic symptoms may occur.ObjectivesThis research study assessed the effects of a strength exercise intervention on balance impairment and gait disturbance amongst individuals living with HIV-associated DSPN.MethodThe study was a single-blinded, randomised controlled trial (RCT) with participants sourced from four HIV centres in Kano metropolis, Nigeria. The intervention was supervised and included progressive resistance exercise (PRE) (three 40-min sessions per week for 12 weeks) using a quadriceps bench (n = 44). The control group (CG) included the non-exercise group (n = 47). The two groups continued to receive routine care. Data were summarised and analysed using inferential statistics (SPSS version 20 program) with the alpha level set at < 0.05.ResultsAt 12 weeks, the results revealed significant improvement with regard to balance performance (p = 0.001) and walking ability (p = 0.001) in the training group. In contrast, no significant differences in balance (P = 0.677) or gait (P = 0.578) were observed in the CG.ConclusionThe findings suggest that PRE is beneficial for balance impairment and gait disturbance caused by neuropathy in persons living with HIV and receiving antiretroviral drugs.