Threshold Electrical Stimulation Research Articles

Removal of grade IV vestibular schwannomas by retrosigmoid approach: results of a cumulative series of two European centers

Introduction The aim of our study was to study the association between end-of-surgery facial nerve stimulation threshold and extent of tumor resection in case of grade IV vestibular schwannomas. Materials and methods Grade IV VSs represent a surgical challenge as a risk/benefit ratio must be considered in balancing a satisfactory extent of resection against a good postoperative functional outcome. We reviewed a cumulative series of 57 patients with large/giant VSs who were operated on by retrosigmoid approach in the period from 2008 to 2018 in two European centers, namely San Filippo Neri Hospital, Rome, Italy and Masaryk Hospital, Usti nad Labem, Czech Republic. Extent of resection, intraoperative direct electrical stimulation threshold of facial nerve and postoperative facial outcome were examined. Results Total or near-total resection was accomplished in 40 (75.5%) cases. Two groups were compared: total or near-total resection (T + NT) and subtotal resection (ST); the end-of-surgery facial nerve stimulation threshold significantly differed (T + NT: 0.24 mA, ST: 0.44 mA, p = 0.036). A critical cutoff was found at 0.2mA; values similar or inferior to this correctly predicted total or near-total resection in 86.7% of cases. Thirty (56.6%) patients had a normal postoperative facial outcome (HB1). Among the 40 patients in T + NT group, 32 (80%) retained an acceptable facial function (HB1-2). Conclusions Lower facial nerve stimulation thresholds positively predict a broader extent of resection and total or -near total resection should be accomplished in such cases. Judicious (subtotal) resection is preferred if threshold values increase while dissecting firmly adherent tumors.

Electrical stimulation thresholds differ between V1 and V2.

Cortical visual prostheses are designed to treat blindness by restoring visual perceptions through artificial electrical stimulation of the primary visual cortex (V1). Intracortical microelectrodes produce the smallest visual percepts and thus higher resolution vision - like a higher density of pixels on a monitor. However, intracortical microelectrodes must maintain a minimum spacing to preserve tissue integrity. One solution to increase the density of percepts is to implant and stimulate multiple visual areas, such as V1 and V2, although the properties of microstimulation in V2 remain largely unexplored. We provide a direct comparison of V1 and V2 microstimulation in two common marmoset monkeys. We find similarities in response trends between V1 and V2 but differences in threshold, neural activity duration, and spread of activity at the threshold current. This has implications for using multi-area stimulation to increase the resolution of cortical visual prostheses.

Atropine facilitates water-evoked swallows via central muscarinic receptors in anesthetized rats.

Anticholinergic medication causes impaired swallowing with hyposalivation. However, the underlying mechanisms by which these drugs modulate the swallowing reflex remain unclear. This study investigated the effects of the muscarinic acetylcholine receptor (mAChR) nonspecific antagonist atropine on the initiation of swallowing. Experiments were performed on 124 urethane-anesthetized rats. A swallow was evoked by either topical laryngeal application of a small amount of distilled water (DW), saline, citric acid, or capsaicin; upper airway distention with a continuous airflow; electrical stimulation of the superior laryngeal nerve (SLN); or focal microinjection of N-methyl-d-aspartate (NMDA) into the lateral region of the nucleus of the solitary tract (L-nTS). Swallows were identified by electromyographic bursts of the digastric and thyrohyoid muscles. Either atropine, the peripheral mAChR antagonist methylatropine, or antagonists of mAChR subtypes M1-M5 were intravenously delivered. Atropine at a dose of 1 mg/kg increased the number of DW-evoked swallows compared with baseline and did not affect the number of swallows evoked by saline, citric acid, capsaicin, or upper airway distention. Methylatropine and M1-M5 antagonists did not significantly change the number of DW-evoked swallows. Bilateral SLN transection completely abolished DW-evoked swallows, and atropine decreased the swallowing threshold of SLN electrical stimulation. Finally, microinjection of NMDA receptor antagonist AP-5 into the L-nTS inhibited DW-evoked swallows, and atropine facilitated the initiation of swallowing evoked by NMDA microinjection into this region. These results suggest that atropine facilitates DW-evoked swallows via central mAChR actions.NEW & NOTEWORTHY Atropine facilitated the distilled water (DW)-evoked swallows in anesthetized rats. Atropine decreased the swallowing threshold evoked by electrical stimulation of the superior laryngeal nerve, which is a primary sensory nerve for the initiation of DW-evoked swallows. Atropine facilitated the swallows evoked by N-methyl-d-aspartate microinjection into the lateral region of the nucleus of the solitary tract, which is involved in the DW-evoked swallows. We speculate that atropine facilitates the DW-evoked swallows via central muscarinic receptor actions.

Soft silicone‐based neural interface to modulate bladder function: chronic studies in awake behaving cats

Direct bladder wall stimulation has been attempted for decades to restore bladder function in people with spinal cord injury and other voiding dysfunctions. However, these efforts were limited by co‐activation of the urethra, legs and other pelvic organs at stimulus intensities that evoked bladder contractions. Neural interfaces for the detrusor muscle itself face several challenges due to its structure and the volume changes it undergoes in normal function. We designed a stretchable silicone net that can be placed around the bladder body to anchor a soft electrode array that interfaces directly with the base of bladder to generate bladder contractions.We created implantable versions of the electrode nets and tested them in chronic experiments. We implanted 5 healthy cats (4 females, 1 male) and tested them with and without anesthesia for 2‐3 months. A pressure catheter was implanted into the bladder to control volume and measure pressure.Bladder wall stimulation through various electrode configurations (monopolar, bipolar), temporal patterns (single electrode, sequential stimulation of multiple electrodes) and stimulus intensities were able to generate complete bladder emptying. In behaving cats, bladder wall stimulation at many different stimulus intensities elicited efficient voiding at physiological bladder pressures (med: 41, IQR: 27‐60 cmH2O). However, there was little relationship (r<0.28) between stimulation amplitude and bladder pressure itself. Rather, stimulation amplitude had an effect on the time between stimulation onset and bladder contraction onset. At low stimulation amplitudes, there was a longer time between stimulation onset and voiding (med: 35s, IQR: 13.5‐68.2s) than occurred at higher amplitudes, which evoked more rapid voiding (med: 23s, IQR: 10‐45s). This contrasts with anesthetized tests, where stimulation at 3 ± 2 mA evoked increases in bladder pressure up to 35 cmH2O. These results suggest that stimulation of the bladder wall recruits sensory pathways leading to an urge to void, but that can be suppressed by the animals. For most of the duration of the implants, stimulation evoked functional voiding with consistent electrical stimulation thresholds. However, after several months there was a failure of an implanted bond that limited the overall duration of the implants.Chronic experiments demonstrate that these electrode nets can be used as a neural interface to generate or initiate comfortable, complete bladder emptying in awake behaving cats. Future efforts include understanding the effects of evoked sensations on voiding and improving the integrity of the bonding between the flexible conductors and the lead wire.

Sex and age differences in sensory threshold for transcutaneous electrical stimulation

Resumo Introdução A dor é um dos principais sintomas preva-lentes na maioria das patologias. A estimulação elétrica ervosa transcutânea (TENS) se apresenta não apenas como medida terapêutica, como também um meio de quantificar a percepção neurossensitiva e dolorosa em pacientes com dores crônicas. Objetivo Avaliar a relação entre sexo e idade com os limiares neurossensitivos (limiar sensitivo e limiar de tolerância) na aplicação da corrente terapêutica TENS, em pacientes com dores crônicas. Métodos Foram selecionados 45 pacientes com dores crônicas (30 mulheres), com idade entre 24 e 87 anos. Cada paciente respondeu ao Questionário Individual, ao Questionário McGill de Dor (MPQ) e ao Inventário de Depressão de Beck (BDI). Posteriormente, aplicou-se a corrente elétrica TENS, pela qual foram analisados o limiar sensitivo e doloroso, bem como a percepção de acionamento das vias neurossensitivas para cada indivíduo. Os dados foram analisados pelo pacote SPSS 24.0 for Windows. Resultados Não houve correlação significativa (p > 0,05) entre possível diagnós-tico depressivo e a percepção da corrente pelos limiares de sensibilidade e dor. Em relação ao sexo, houve diferença significativa nos limiares sensitivos (p = 0,003) entre homens e mulheres. Já para a queixa de dor e limiar de dor, não foram observadas diferenças estatísticas entre os sexos (p > 0,05). Para as análises correlacionais, identificou-se correlação significativa (p = 0,05) entre as variáveis de índice de massa corporal e limiar de tolerância à dor (r = 0,68) para o sexo feminino e idade e limiar sensitivo (r = 0,65) paro o sexo masculino. Conclusão As diferenças identificadas entre os limiares de sensibilidade entre os sexos, onde as mulheres identificaram o estímulo elétrico significativamente primeiro que os homens, podem auxiliar nas doses de intensidade ou tipo de corrente terapêutica dos pacientes.

Wenxin Granules Regulate Endoplasmic Reticulum Stress Unfolded Protein Response and Improve Ventricular Remodeling on Rats with Myocardial Infarction.

Background. Arrhythmia after myocardial infarction is the leading cause of death in clinical heart disease. Increasing studies have shown that the response to endoplasmic reticulum (ER) stress (ERS) caused by myocardial infarction is related to prognosis and the development of arrhythmias. The unfolded protein response (UPR) could serve as an important regulatory signaling pathway following myocardial infarction. The traditional Chinese medicine Wenxin Granules improve arrhythmias following myocardial infarction, which may be related to ERS intervention and the activation of the UPR and apoptosis. We aimed to investigate the involvement of Wenxin Granules in the activation of the UPR and apoptosis following myocardial infarction. Left coronary artery ligation was established as a rat model of myocardial infarction. The rats were randomly divided into the model group, low-dose Wenxin Granule group, high-dose Wenxin Granule group, and metoprolol group. Rats with only wire insertion and no ligature were used as the sham group. Small animal ultrasound systems were used to detect changes in heart structure and function, and the electrical stimulation threshold for ventricular fibrillation was detected. The expression of glucose-regulated protein (GRP)78, activating transcription factor (ATF)6, X-box binding protein (XBP)1, protein kinase–like ER kinase (PERK), phosphorylated (p)-PERK, Bax, Bcl2, C/EBP homologous protein (CHOP), caspase 12, caspase 8, and caspase 3 were detected by western blot, and terminal deoxynucleotidyl transferase dUTP Nick end labeling (TUNEL) was used to determine the cardiomyocyte apoptosis index. Compared with the sham group, rats in the model group displayed immediate ST-segment elevation and pathological Q waves after 24 hours. After 2 weeks, the left ventricular (LV) anterior wall thickness (LVAW) became thinner, and the inner diameter (LVID) increased. The end-diastolic LVAW (LVAWd), end-systolic LVAW (LVAWs), ejection fraction (EF), and fractional shortening (FS) were significantly reduced (P < 0.01), whereas the LVIDd, LVIDs, diastolic LV volume (LV Vold), and systolic LV volume (LV Vols) significantly increased (P < 0.01). The ventricular fibrillation threshold decreased significantly (P < 0.01). ERS proteins GRP78, p-PERK, PERK, ATF6, and XBP1 and apoptotic proteins CHOP, Bax, caspase 12, caspase 8, and caspase 3 significantly increased (P < 0.01, P < 0.05), whereas Bcl-2 expression and the Bcl-2/Bax ratio decreased (P < 0.01). Compared with the sham group, LVAWd, LVAWs, FS, and Bcl-2 protein expression were significantly increased in the low-dose Wenxin Granule group (P < 0.01, P < 0.05), and p-PERK and ATF6 decreased (P < 0.01, P < 0.05). Compared with the sham group, LVAWd, LVAWs, EF, FS, and the ventricular fibrillation threshold significantly increased in the high-dose Wenxin Granule and metoprolol groups (P < 0.01, P < 0.05), whereas LVIDs, LV Vols, and ERS proteins were significantly decreased (P < 0.01, P < 0.05). CHOP, Bax, caspase 12, caspase 8, and caspase 3 protein expression decreased in the Wenxin Granule group (P < 0.01, P < 0.05), whereas Bcl-2 and the Bcl-2/Bax ratio increased (P < 0.01, P < 0.05). LVIDd and Bax decreased in the metoprolol group (P < 0.01, P < 0.05), and the Bcl-2/Bax ratio increased (P < 0.05). The cardiomyocyte apoptosis index values for the low- and high-dose Wenxin Granule and metoprolol groups were significantly reduced (P < 0.05). This study suggested that the UPR is an essential mechanism underlying pathological injury after myocardial infarction. Wenxin Granule treatment can improve ventricular remodeling and cardiac function and inhibit arrhythmia by preventing excessive ERS from activating the UPR and apoptosis.

Implantable Closed-Loop System for Restoration of Blinking in Case of Unilateral Facial Nerve Paralysis.

Background:In facial nerve (FN) paralysis, a critical task is to restore the orbicularis oculi muscle (OOM) function to prevent corneal atrophy and vision deterioration. In this study, we present the application of a fully implantable bioelectrical closed-loop system for the restoration of blinking in a rabbit model of unilateral FN paralysis. We test the hypothesis that blinking events on the healthy side of a face could be used to trigger an electrical stimulation of eyelid muscles on the impaired side of the face resulting in functional simultaneous blinking.Methods:We developed and tested in an animal model a functional prototype of a fully implantable closed-loop device for the restoration of blinking in patients with unilateral FN paralysis. The study was performed on 14 rabbits after complete transection of the FN on 1 side. The animals were divided into 2 groups. In the first group, the subcutaneous electrodes were implanted for functional electrical stimulation of the upper eyelid on the side of the damaged OOM, and the electromyographic signals (EMG) from the healthy OOM were recorded. Two-phase stimulation pulses with adjustable parameters were delivered between electrodes in the medial and lateral corners of a palpebral fissure. Animals from the second group had not received any treatment and were used as a control for facial paralysis.Results:Stimulation parameters that were sufficient to cause complete eyelid closure were estimated. These parameters included pulse current amplitude, pulse width, and stimulation frequency. We also report the modulation of stimulation parameters during the stimulation period (days 8-30 post transection of the FN). The absence of the eyelid closure in the control group after 1 month of denervation was confirmed.Conclusion:Our study confirmed the possibility of restoration of simultaneous complete eyelid closure by a pre-pain threshold electrical stimulation using a fully implantable closed-loop device in animals with unilateral FN paralysis.

Analgesic and Cardiopulmonary Effects of Epidural Romifidine and Morphine Combination in Horses

The study aim is to compare the effects of epidural administration of two different doses of romifidine combined with morphine in horses. A prospective crossover blinded experimental design was used. Five adult healthy horses two males and three females with a mean body weight of 380 ± 45 Kg (335–425 kg), were studied. Treatments consisted of romifidine 30 μg/kg (R30) or 60 μg/kg (R60) combined with morphine 0.1 mg/kg with a washout interval of 72 hours, administered through an epidural catheter placed at the first intercoccygeal space. Heart rate (HR) and respiratory rate (fR), pH, blood gases, arterial blood pressures (mmHg), and threshold for electrical noxious stimulation was evaluated for 120 minutes and after 240 minutes of epidural injection. Data were collected before injections and every 15 minutes for 120 minutes, and at 240 minutes of epidural administration. Significant sedation occurred in both treatments with no statistically significant difference between them. There were significant changes in fR and HR from baseline but no difference between treatments. Arterial blood pressures were significantly lower in R60 treatment from 75 up to 120 minutes post epidural injection. Analgesia was considered moderate for both treatments lasting longer with romifidine at 60 μg/kg. Epidurally administered romifidine and morphine combination in horses produces dose-dependent sedation, arterial hypotension, and antinociceptive effects.

The Effects of Electrical Stimulation on Gross Motor Function in Children with Spastic Cerebral Palsy: A Review Article

Cerebral Palsy (CP) is the most common childhood disability in children. The child’s motor development and functioning are affected by variety neuromuscular and musculoskeletal impairments. Both of upper and lower extremities motor function are important for many daily life activities. For example, children who has good fine motor function and who can sitting independently can manipulate the objects by using upper extremities and can realize transfer activities. Therefore, she/he can play effectively in daily life. Children who can play will be happy and independent in daily life activities. Spasticity is the most common problem in children with CP and can interfere with daily life activities. Children who have spastic CP constrained in daily life activity, participation and recreational activities. Working on gross motor skills helps to gain strength, increase postural control, to achieve motor milestones and to become independent in daily life activities. In treatment program, physical therapist used different approach, like, exercise programs (stretching, strengthening, aerobic exercise…), electrical stimulation, neurodevelopmental approaches, virtual reality, constrained induced movement therapy. Neuromuscular Electrical Stimulation, Functional Electrical Stimulation and Threshold Electrical Stimulation commonly used for this reason. There is a few evidence on positive effects of electrical stimulation applied in children with CP. This review study was planned to investigate the effects of electrical stimulation on gross motor function in children with CP.

Double-binding botulinum molecule with reduced muscle paralysis: Evaluation in in vitro and in vivo models of migraine

With a prevalence of 15%, migraine is the most common neurological disorder and among the most disabling diseases, taking into account years lived with disability. Current oral medications for migraine show variable effects and are frequently associated with intolerable side effects, leading to the dissatisfaction of both patients and doctors. Injectable therapeutics, which include calcitonin gene–related peptide–targeting monoclonal antibodies and botulinum neurotoxin A (BoNT/A), provide a new paradigm for treatment of chronic migraine but are effective only in approximately 50% of subjects. Here, we investigated a novel engineered botulinum molecule with markedly reduced muscle paralyzing properties which could be beneficial for the treatment of migraine. This stapled botulinum molecule with duplicated binding domain—binary toxin-AA (BiTox/AA)—cleaves synaptosomal-associated protein 25 with a similar efficacy to BoNT/A in neurons; however, the paralyzing effect of BiTox/AA was 100 times less when compared to native BoNT/A following muscle injection. The performance of BiTox/AA was evaluated in cellular and animal models of migraine. BiTox/AA inhibited electrical nerve fiber activity in rat meningeal preparations while, in the trigeminovascular model, BiTox/AA raised electrical and mechanical stimulation thresholds in Aδ- and C-fiber nociceptors. In the rat glyceryl trinitrate (GTN) model, BiTox/AA proved effective in inhibiting GTN-induced hyperalgesia in the orofacial formalin test. We conclude that the engineered botulinum molecule provides a useful prototype for designing advanced future therapeutics for an improved efficacy in the treatment of migraine.

Electrical Stimulation Therapy as Treatment for Poststroke Dystonia

This case describes success using high-dose submotor threshold electrical stimulation (EStim) therapy for the management of dystonia in a chronic stroke patient. The authors find this novel EStim treatment is safe and offers the potential to manage poststroke dystonic movements.

Double-Binding Botulinum Molecule with Reduced Muscle Paralysis: Evaluation in In Vitro and In Vivo Models of Migraine

With a prevalence of 15%, migraine is the most common neurological disorder and among the most disabling diseases, taking into account years lived with disability. Current oral medications for migraine show variable effects and are frequently associated with intolerable side effects, leading to the dissatisfaction of both patients and doctors. Injectable therapeutics, which include calcitonin gene–related peptide–targeting monoclonal antibodies and botulinum neurotoxin A (BoNT/A), provide a new paradigm for treatment of chronic migraine but are effective only in approximately 50% of subjects. Here, we investigated a novel engineered botulinum molecule with markedly reduced muscle paralyzing properties which could be beneficial for the treatment of migraine. This stapled botulinum molecule with duplicated binding domain—binary toxin-AA (BiTox/AA)—cleaves synaptosomal-associated protein 25 with a similar efficacy to BoNT/A in neurons; however, the paralyzing effect of BiTox/AA was 100 times less when compared to native BoNT/A following muscle injection. The performance of BiTox/AA was evaluated in cellular and animal models of migraine. BiTox/AA inhibited electrical nerve fiber activity in rat meningeal preparations while, in the trigeminovascular model, BiTox/AA raised electrical and mechanical stimulation thresholds in Aδ- and C-fiber nociceptors. In the rat glyceryl trinitrate (GTN) model, BiTox/AA proved effective in inhibiting GTN-induced hyperalgesia in the orofacial formalin test. We conclude that the engineered botulinum molecule provides a useful prototype for designing advanced future therapeutics for an improved efficacy in the treatment of migraine.

SPARC ‐ The Functional Anatomy of Murine Myelinated Renal Afferents

Perhaps because they are a small minority of the total population of renal afferents, myelinated renal afferents (MRA ) have been the least studied. Yet, they are promising targets for neuromodulation because of their low thresholds for electrical stimulation. We are studying the calibers, branching patterns, terminal morphologies, and intrarenal targets of MRA. We identify the myelin sheaths and axons of MRA using antibodies to myelin protein zero and heavy‐chain neurofilament, respectively. The diameters of a majority of MRA range between 1 and 4 u. The diameters of a small minority range between 6 and 10u. Thus, the diameters of MRA are distinctly bimodal. Unmyelinated terminal segments of MRA arise from the myelinated segments of axons at two sites. First, an unmyelinated segment of axon projects from the end of each MRA. Second, unmyelinated segments arise as axon collaterals at nodes of Ranvier along the course of the myelinated axon. Most unmyelinated segments end without any terminal specialization. However, some terminate in small “bulbs, that are approximately twice the diameter of the axon. We have not observed receptor‐related, connective tissue specializations surrounding either type of termination. The distal myelinated portions of MRA are frequently tortuous, sometimes forming hairpin turns and loops. These complex features result in spatial concentrations of nodes of Ranvier, concentrations of unmyelinated collaterals, and concentrations of receptors. A marked narrowing at the origin of each unmyelinated segment suggests the presence of a spike‐initiation zone. The majority of MRA terminate deep in the renal cortex, most often in the extracellular space and frequently within bundles of connective tissue. Some terminations closely appose, but never penetrate, the renal tubular system. However, a small number of MRA appear to penetrate the walls of small arteries and venules. Terminations of MRA show no consistent relationship to glomeruli. The functions of MRA are, thus far, uncertain. Their terminations in the extracellular space would permit them to respond to changes in the composition of the extracellular fluid. However, their associations with connective tissue in the extracellular space could also provide them with mechanoreceptor properties. Their presence in the walls of the vasculature could mediate either chemoreceptor or mechanoreceptor functions. The distinctly bimodal distribution of the diameters of MRA suggests that they may participate in more than one physiological function. From a clinical perspective, the differences in stimulation thresholds afforded by those differences in axon caliber could facilitate selective neuromodulation of multiple physiological processes.Support or Funding InformationSupported by SPARC Award 1U01DK116320‐02, JW Osborn, Jr., PI

The effect of oral administration of monosodium glutamate on epileptogenesis in infant rats.

Glutamate is an excitatory neurotransmitter that is widely distributed throughout the brain. An increase in glutamate concentration or sensitivity of glutamate receptors triggers neurodegenerative diseases, epilepsy in particular. Monosodium glutamate is a substance added to foods to enhance flavour. We investigated the effect of monosodium glutamate on epileptogenesis, as well asheight and weight, in rats that were just weaned. Twenty-four male and female 21-day-old Wistar Albino rats were divided into two groups: one with monosodium glutamate added to the drinking water, and a control in which NaCl was added to the drinking water. The electrical stimulation threshold values were determined in animals to which the hippocampal kindling process was applied, and the stimulations at these threshold values were invariably applied to the animals until they were kindled. The electrical stimulation threshold values of the monosodium glutamate group did not statistically change, whereas the number of required stimulations for kindled rats was significantly lower compared with the control group. These results reveal that long-term oral administration of glutamate salts causes an increase in excitability in the central nervous system during ontogenetic development.

Resveratrol suppresses nociceptive jaw-opening reflex via 5HT3 receptor-mediated GABAergic inhibition

Systemic administration of the dietary constituent, resveratrol, was previously shown to inhibit the nociceptive jaw-opening reflex (JOR) via the endogenous opioid system. The present study investigated whether resveratrol could similarly affect the JOR under in vivo conditions via 5HT3 receptor-mediated GABAergic inhibition. We used electrical stimulation of the tongue in pentobarbital-anesthetized rats to evoke the JOR, which was recorded as the anterior belly of the digastric muscle electromyograms (dEMG). Intravenous administration of resveratrol (2 mg/kg) reduced the dEMG amplitude in response to three times the determined threshold electrical stimulation, with maximum inhibition reached within approximately 10 min. These inhibitory effects on the JOR were reversible to control levels after approximately 20 min. Pretreatment of rats with either 5HT3 receptor antagonist, ondansetron (0.25−1 mg/kg, i.p.), or GABAA receptor antagonist, bicuculline (0.5−1 mg/kg, i.p.), significantly and dose-dependently attenuated the inhibitory effects of resveratrol on dEMG amplitude compared with untreated controls. These findings suggest that resveratrol also attenuates the nociceptive JOR via 5HT3 receptor-mediated GABAergic inhibition. The present study therefore provides new insight into a possible mechanism underlying resveratrol-induced trigeminal antinociception via the descending pain control system and highlights a potential therapeutic agent for complementary alternative medicine.

Normal High HbA1c a Risk Factor for Abnormal Pain Threshold in the Japanese Population.

Purpose: Small fiber dysfunction is common in subjects with diabetic polyneuropathy (DPN). It is unsettled, however, whether marginal glucose intolerance is implicated in the onset and progression of small fiber dysfunction. Herein, we explored the relationship between glycated hemoglobin levels (HbA1c) and pain sensation in the Japanese population.Methods: A population-based study of 894 individuals (352 men, 542 women; average age 53.8 ± 0.5 years) and 55 subjects with impaired fasting glucose (IFG) in the 2017 Iwaki project were enrolled in this study. Individuals with diabetes were excluded. Relationships between pain threshold for intraepidermal electrical stimulation (P-IES) and parameters associated with metabolic syndrome were examined.Results: P-IES was elevated with increasing of age in women but not in men. Average P-IES (mA) was increased in IFG subjects (n = 55, 0.20 ± 0.03) compared with normoglycemic/non-IFG individuals (n = 894, 0.15 ± 0.01) (p < 0.01). It was comparable between IFG and a group of normal high HbA1c (5.9–6.4%). Univariate linear regression analyses showed no influence of sex, triglyceride, or cholesterol on the value of P-IES. In contrast, there were significant correlations between P-IES and serum HbA1c level (ß = 0.120, p < 0.001) Adjustments for the multiple clinical measurements confirmed positive correlation of P-IES with HbA1c (ß = 0.077, p = 0.046).Conclusion: Individuals with normal high HbA1c exhibited an elevated P-IES in a healthy Japanese population which may be useful for the screening of subclinical DPN.

Electromyographic Response of Facial Nerve Stimulation Under Partial Neuromuscular Blockade During Resection of Vestibular Schwannoma

To evaluate whether use of partial nondepolarizing neuromuscular blocking agents, at a train-of-four level 1, compromise facial nerve monitoring during vestibular schwannoma (VS) resection. Sixty consecutive patients undergoing VS resection were enrolled into a partial peripheral neuromuscular blockade group or free of neuromuscular blockade group. Stimulation threshold to elicit an electromyographic response amplitude of at least 100 μV was recorded at the proximal and distal facial nerve after VS removal. The proximal-to-distal ratio of amplitude of the orbicularis oculi and oris muscles was calculated. All patients successfully passed the electromyography monitoring test. Mean electrical stimulation thresholds were higher in the peripheral neuromuscular blockade group than in the free of neuromuscular blockade group (0.12 mA vs. 0.06 mA at proximal site, P= 0.001; 0.08 mA vs. 0.03 mA at distal site, P= 0.0002). The differences in median proximal-to-distal amplitude ratios were not statistically significant in both groups. There was a trend toward more patients needing phenylephrine. Recovery profiles were comparable in the 2 groups. Although mean stimulation threshold to elicit a response amplitude was higher in the peripheral neuromuscular blockade group than in the free of neuromuscular blockade group at the proximal site, the stimulation thresholds in both groups were sufficient for facial nerve monitoring in VS surgery, indicating no clinical difference in both groups.

The optimal and safe intensity for facial nerve stimulation during intraoperative neuromonitoring in middle ear surgery

ObjectiveThis study aimed to investigate the optimal and safe intensity for facial nerve stimulation during middle ear surgery.MethodsThirty-seven patients who had their facial nerve exposed prior to surgery were prospectively enrolled in this study, and electromyography (EMG) recordings were obtained from the orbicularis oculi and orbicularis oris muscles. Four pigs were also enrolled in an animal study, and continuous stimulation was performed on the facial nerves of the pigs for 10 minutes. The EMG responses were measured and the pathologic outcomes of the facial nerve after stimulation were determined.ResultsIn the human study, the mean intensity of the minimal electrical stimulation threshold was 0.21 mA (range: 0.1–0.3 mA). A linear correlation was observed between stimulus intensity and response amplitude for intensities below 0.4 mA. Response amplitudes reached a plateau between 0.4 mA and 1.0 mA. The minimal stimulus intensity that could generate a maximal response was 0.4 mA in the orbicularis oculi (244 μV) and orbicularis oris (545 μV). In the animal study, there were no observed changes in EMG or nerve damage incidence after the continuous stimulation of 3.0 mA.Conclusions0.4 mA is considered to be the optimal intensity of facial nerve stimulation during middle ear surgery, and it was estimated through the animal study that a stimulation of 3.0 mA is safe from facial nerve damage.

Sensory Amplitude Electrical Stimulation via Sock Combined With Standing and Mobility Activities Improves Walking Speed in Individuals With Chronic Stroke: A Pilot Study.

Objective: To determine if sensory amplitude electrical stimulation (SES) delivered via sock electrode combined with standing and mobility activities improved gait speed, sensation, balance, and participation in chronic stroke. It was hypothesized that SES would enhance the effectiveness of exercise, resulting in reduced impairment and improved function.Design: Case Series.Setting: Home-based intervention.Participants: Thirteen adults (56.5 + 7.84 years old) with chronic stroke (8.21 + 4.36 years post) and hemiparesis completed the study. Participants were community ambulators.Intervention: Participants completed 6 weeks of self-administered SES delivered via sock electrode concurrent with standing and mobility activities for a minimum of 5 days/week for 30-min, twice daily.Outcome Measures: Berg Balance Scale (BBS), Stroke Rehabilitation Assessment of Movement—LE subscale (STREAM), 10 Meter Walk Test (10 MWT), Activities-Specific Balance Confidence Scale (ABC), Stroke Impact Scale (SIS), Perceptual Threshold of Electrical Stimulation (PTTES), and Monofilament testing were administered at pre-test, post-test, and 3-month follow up.Results: Baseline sensory scores and change scores on functional outcomes were analyzed using Pearson Product-Movement Correlation Coefficients, Friedman test, and Linear mixed models. There was a significant change with 10 MWT self-selected pace (Friedman's p = 0.038). Pre-post intervention changes in other outcome measures were not significant. According to the Cohen's effect size classification, there were medium effect sizes for both the STREAM-LE and Monofilaments.Conclusion: The use of home-based SES via sock electrode combined with standing and mobility activities may contribute to improve gait speed in chronic stroke.

Assessment of anesthetic properties and pain during needleless jet injection anesthesia: a randomized clinical trial.

Pain due to administration of local anesthetics is the primary reason for patients' fear and anxiety, and various methods are used to minimize it. This study aimed to measure the degree of pain during administration of anesthesia and determine the latency time and duration of pulpal anesthesia using two anesthetic methods in the maxilla.Materials and Methods:A randomized, single-blind, split-mouth clinical trial was conducted with 41 volunteers who required class I restorations in the maxillary first molars. Local anesthesia was administered with a needleless jet injection system (experimental group) or with a carpule syringe (control) using a 30-gauge short needle. The method of anesthesia and laterality of the maxilla were randomized. A pulp electric tester measured the latency time and duration of anesthesia in the second molar. Visual analogue scale (VAS) was used to measure the degree of pain during the anesthetic method. Data were tabulated and then analyzed by a statistician. The t-test was used to analyze the differences between the groups for basal electrical stimulation. Duration of anesthesia and degree of pain were compared using the Mann-Whitney test. A 5% significance level was considered.Results:There was no statistical difference in the basal electrical stimulation threshold (mA) and degree of pain between the two methods of anesthesia (p>0.05). Latency time was 2 minutes for all subjects. The duration of pulpal anesthesia showed no statistical difference (minutes) between the two methods (p<0.001), with a longer duration for the traditional method of anesthesia (median of 40 minutes).Conclusions:The two anesthetics methods did not differ concerning the pain experienced during anesthesia. Latency lasted 2 minutes for all subjects; the traditional infiltration anesthesia resulted in a longer anesthetic duration compared with the needleless jet injection.