Transdermal Electrical Stimulation Research Articles

Nociceptive threshold measurement as a non‐invasive functional test of an epidural injection in a dog

AbstractWe present a case of a 3‐year‐old, male Border Collie with severe hip dysplasia and osteoarthritis undergoing total hip replacement, notably having a history of a previous hip surgery with inadequate epidural analgesia. Our objective was to evaluate epidural efficacy before surgery using nociceptive threshold measurement. Nociceptive thresholds were measured with transdermal electrical stimulation via the Dolosys Pain Tracker device. The dog received epidural ropivacaine and morphine, resulting in a cessation of withdrawal response and electromyographic activity. This effect was confirmed under anaesthesia. Postoperatively, the dog recovered without relevant complications. In conclusion, nociceptive threshold measurement using the Dolosys Pain Tracker device allowed immediate confirmation of epidural efficacy, reducing the risk of intraoperative analgesic inadequacy. This approach may enhance surgical pain management in challenging cases.

Abstract 58: The 5-HT7 receptor contributes to increased hindquarter blood flow caused by skeletal muscle contraction

Exogenous serotonin (5-hydroxytryptamine, 5-HT) causes a reproducible decrease in blood pressure in normotensive and hypertensive rats. This is associated with dilation of arterioles in skeletal muscle. The 5-HT7 receptor KO rat strain allowed us to test the role of this receptor in both responses as well as the effects of endogenous 5-HT -- acting at 5-HT7 receptors -- on normal circulatory regulation. First, we hypothesized that the 5-HT7 receptor KO rat would have a higher hindquarter (HQ) vascular resistance (HQVR) than wildtype (WT) because of loss of this receptor. In rats anesthetized with isoflurane, instrumented with arterial catheters and flow probes on the terminal aorta, male KO rats had significantly higher resting HQVR [mm Hg/ml/min; KO (16.0±2.0) vs WT (10.8±0.6.0), p = 0.04] and lower HQ blood flow than normal Sprague-Dawley (SD) rats. No differences in resting HQVR or HQ flow were observed in female rats. Intravenous infusion of 5-HT (50 ug/kg/min) reduced systemic blood pressure and HQVR; these parameters were significantly attenuated (~56%) in male KO rats versus WT and SD animals. In females, falls in systemic blood pressure and HQVR were absent in both KO and WT rats. Second, as 5-HT has been implicated in the pathophysiology of heart failure (HF), a left anterior descending artery ligation model of HF was used to investigate the potential role of 5-HT7 regulation of HQ flow in HF-associated exercise intolerance. The ability of hindlimb muscle stimulation to increase blood flow using transdermal neuromuscular electrical stimulation was tested (NMES). M and F KO rats showed a reduced ability to increase HQ flow during muscle contraction vs WT (% over basal: M WT = 118±18 vs KO =14.6±7.1; F WT= 101±12 vs KO = 7.6±6) rats. This was observed in both intact and HF rats (in which flow changes were already impaired). Acute administration of the 5-HT7 receptor antagonist SB269970 abolished the ability of NMES to increase HQ flow in normal SD rats. Importantly, the microcirculatory capacity, visualized by Lectin-594, was not significantly different in the gastrocnemius muscle of WT (arbitrary fluorescence units/area: 946±40) vs KO (914±69). These data support that the 5-HT7 receptor, likely activated by endogenous 5-HT, is an important regulator of skeletal muscle vascular resistance. Thus, 5-HT may have a larger role in normal and pathophysiological regulation of the circulation than has previously been appreciated.

Enhanced transport of brain interstitial solutes mediated by stimulation of sensorimotor area in rats.

Solute transport in the brain is essential for maintaining cerebral homeostasis. Recent studies have shown that neuronal activity enhances the transport of cerebrospinal fluid solutes, but its impact on interstitial solute transport has not been established. In this study, we investigated whether neuronal activity affects the transport of interstitial solutes. Fluorescent Texas Red ovalbumin was injected intracortically into the unilateral sensorimotor area of the Sprague-Dawley rats. Regional neuronal activity around the injection site was elicited by transdermal electrical stimulation of a corresponding forelimb for 90 min ( n = 6). The control group of rats ( n = 6) did not receive any electrical stimulation. Subsequently, the spatial distributions of the tracer over the cortical surface and from the brain sections were imaged and compared between two groups. The ovalbumin fluorescence from the cervical lymph nodes was also compared between the groups to evaluate the effect of neuronal activity on solute clearance from the brain. Tracer distribution over the brain surface/sections revealed a significantly higher uptake of ovalbumin in the hemisphere ipsilateral to the injection among the stimulated animals compared to the unstimulated group. This difference, however, was not seen in the hemisphere contralateral to injection. A trace amount of ovalbumin in the lymph nodes was equivalent between the groups, which indicated a considerable time needed for interstitial solutes to be drained from the brain. The results suggest that neuronal activity enhances interstitial solute transport, calling for further examination of ultimate routes and mechanisms for brain solute clearance.

Behaviorally Inhibited Individuals Learn to Avoid Transdermal Stimulation More Quickly, and this Learning Is Accelerated Throughout the Study

Information on how behavioral inhibition (BI) affects the amount of time it takes an individual to avoid a stressful situation could answer many questions about anxiety disorders and whether BI influences avoidance behavior. BI is a temperament characteristic associated with increased vulnerability to stress compared to their non-behaviorally inhibited (NBI) counterparts. Our previous study demonstrated that BI individuals have lower heart rate variability (HRV) than NBI individuals. This suggests that BI individuals have significantly less parasympathetic nervous system (PNS) output at rest; however, it is unknown how BI affects avoidance acquisition using a mildly stressful stimulus. Previous studies have shown differences in the behavior found in Wistar-Kyoto rats, which exhibit BI behavior, compared to Sprague-Dawley control rats. Our current study will test the hypothesis that BI individuals learn to make escape and avoidance responses using subdermal ulnar nerve transdermal electrical stimulation (TES) more rapidly than NBI individuals and also experience a more significant increase in heart rate (HR) and blood pressure (BP). BI individuals were identified through a series of self-reported questionnaires. Three levels (30 mV, 50 mV, and 70 mV) of subdermal ulnar nerve TES were delivered to participants while receiving warning signals that predicted the delivery of the TES. Participants had access to a button that, when pressed during the light, prevented the delivery of the TES. This was scored as an avoidance response. If the button was pressed during the TES, it terminated the stimulation and was scored as an escape. HR and BP were also measured using a BIOPAC data acquisition system during TES. Our preliminary results indicate that BI individuals show a decrease in latency in the amount of time it took them to make an avoidance as the study progressed, while NBI individuals show a slight increase in latency, highlighting the idea that BI individuals are more curious to press the button or they are more likely to want to avoid the TES quicker. We would like to thank the Carthage College Research, Scholarship, and Creativity Committee as well as the Carthage College Neurophysiology Laboratory professors for their continued support throughout the study. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Accurate diagnosis and effective treatment of abnormal meridians in erectile dysfunction patients based on infrared thermography: an electrophysiological technique study.

An increasing body of research has demonstrated that appropriate stimulation of the meridians and acupoints in the human body can play a preventative and therapeutic role in diseases. This study combines the use of infrared thermography with intelligent electrophysiological diagnostic system (iEDS) to accurately diagnose and apply transdermal low-frequency electrical stimulation to treat abnormal meridians in patients with erectile dysfunction (ED). The treatment protocol included 6 treatments (each lasting 30 min and performed twice a week). The International Index of Erectile Function-5 (IIEF-5), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Erection Hardness Scale were used to assess treatment results. A total of 62 patients were included in this study, with 31 patients in the treatment group and 31 patients in the sham therapy group. After six treatments, the treatment group improved significantly in IIEF-5 (15.52 ± 2.06 vs. 18.84 ± 2.67, p < 0.001), PHQ-9 (8.32 ± 6.33 vs. 4.87 ± 4.41, p < 0.001), GAD-7 (5.32 ± 5.08 vs. 2.94 ± 3.31, p = 0.003), and EHS (2.48 (2.00, 3.00) vs. 2.90 (2.00, 3.00), p = 0.007). After six sham treatment sessions, no improvements in any of the scores were reported in the sham therapy group. Following that, this group had an additional six treatments of regular therapy, which resulted in statistically significant improvements in IIEF-5 (16.65 ± 1.96 VS. 19.16 ± 2.40, p < 0.001), PHQ-9 (8.81 ± 6.25 VS. 4.97 ± 4.36, p < 0.001), GAD-7 (5.74 ± 5.18 VS. 3.68 ± 3.42, p < 0.001), and EHS (2.61 (2.00, 3.00) VS. 3.03 (2.00, 4.00), p = 0.003). No adverse events were reported regarding penile discomfort, pain, injury, or deformity. CLINICAL TRIALS: The study protocol is registered in the Clinical Trials Registry with the identification number ChiCTR2300070262.

Efficacy and safety of transdermal electrical stimulation in patients with nonarteritic anterior ischemic optic neuropathy

BackgroundNo effective treatment for NAION with strong evidence has been established till date. The aim of this investigator-led, prospective, non-randomized, open-label, uncontrolled multi-center exploratory clinical trial is to evaluate the efficacy and safety of transdermal electrical stimulation (TdES) using skin electrodes in patients with NAION.MethodsFive patients with monocular NAION underwent TdES (10-ms biphasic pulses, 1.0 mA, 20 Hz, 30 min) of the affected eye six times at 2-week intervals. The primary endpoint was the logarithm of the mini-mum angle of resolution (logMAR) visual acuity at 12 weeks compared with 0 weeks. The secondary endpoints were changes in the best-corrected logMAR visual acuity, Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity, and mean deviation (MD) of the Humphrey field analyzer (HFA) 10–2 and HFA Esterman test scores. Additionally, the safety of TdES was evaluated.ResultsLogMAR visual acuity improved by ≥ 0.1 in two eyes, and ETDRS visual acu-ity improved by ≥ 5 characters in one eye. The mean change in logMAR visual acuity from week 0 showed an increasing trend. The mean MD of HFA 10–2 showed no obvious change, while HFA Esterman score improved in four eyes. All patients completed the study according to the protocol, and no treatment-related adverse events were observed.ConclusionsTdES treatment may have improved visual acuity and visual field in some patients. Further sham-controlled study in larger cohort is needed on its effectiveness.Trial registrationUMIN, UMIN000036220. Registered 15 March, 2019, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000041261.

Comparing psychological and physiological factors involved in perceived threats in behaviorally inhibited individuals

Behavioral inhibition (BI) is a temperament characteristic which is associated with increased vulnerability to stress compared to non-behaviorally inhibited (NBI) counterparts. The physiologic and psychologic substrate which underlies the difference between BI and NBI individuals is unknown. Our previously published study demonstrated that BI individuals have decreased heart rate variability (HRV) relative to NBI individuals suggesting that BI individuals have less parasympathetic nervous system (PNS) output; however, it is unknown how BI affects perceived stress. Our current study tested the hypothesis that BI individuals would have higher perceived stress and physiologic stress during transdermal electrical stimulation (TES). Participants were administered TES beginning at 5mV and increased by 5mV increments until 100mV was reached. We used the Adult Measure of Behavioral Inhibition (AMBI) and the Perceived Stress Scale (PSS) to measure perceived stress, State-Trait Anxiety Inventory (STAI) scores to measure current stress, and a series of self-reported questionnaires to measure BI. Additionally, we used a BIOPAC data acquisition system to measure heart rate (HR), HRV, and blood pressure (BP) to measure physiological stress. Our pilot data suggests there was a non-significant trend of higher perceived stress after TES in BI individuals; however, there was a significant relationship between perceived stress and STAI scores. There was no significant difference in HR, HRV and BP between BI and NBI individuals. In conclusion, our pilot data suggests that a person’s BI or NBI status affects their perceived stress after a stressor is induced. BI individuals will have higher perceived stress after a stressor is presented as opposed to NBI individuals. We will conduct further studies using TES to further study this finding. Identification of these physiological factors could provide an additional mechanism for identifying individuals who are at a higher risk for developing stress and anxiety disorders. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effect of behavioral inhibition on avoidance behavior during transdermal electrical stimulation

Behavioral inhibition (BI) is a temperament characteristic that is associated with increased vulnerability to stress compared to their non-behaviorally inhibited (NBI) counterparts. Our previous study demonstrated that BI individuals have lower heart rate variability (HRV) than NBI individuals. This suggests that BI individuals have significantly less parasympathetic nervous system (PNS) output at rest. However, it is unknown how BI affects avoidance acquisition using a mildly stressful stimulus. Previous studies have shown that there are differences in the behavior found in Wistar-Kyoto rats, which exhibit BI behavior, compared to Sprague-Dawley control rats. Our current study will test the hypothesis that BI individuals learn to make escape and avoidance responses using subdermal ulnar nerve transdermal electrical stimulation (TES) more rapidly than NBI individuals, and also experience a greater increase in heart rate (HR) and blood pressure (BP). BI individuals were identified through a series of self-reported questionnaires. Three levels (30 mV, 50 mV, and 70 mV) of subdermal ulnar nerve TES were delivered to participants while receiving warning signals that predict the delivery of the TES. Participants had access to a button that when pressed during the light the warning signal prevented the delivery of the TES. This was scored as an avoidance response. If the button was pressed during the TES, it terminated the stimulation and was scored as an escape. HR and BP were also measured during TES using a BIOPAC data acquisition system. Our preliminary results do not suggest a difference between BI and NBI individual differences in HR or BP during TES (n=13); however, our future studies will investigate the differences in HRV and the acquisition of avoidance behavior during TES. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Cerebral cortex Functional Networks of Transdermal Electrical Stimulation at Daling (PC7) Acupoint.

The cerebral cortex functional network of Electroencephalogram (EEG) signals during transcutaneous electrical acupoint stimulation (TEAS) on 21 healthy subjects was constructed by using three modules: standard low-resolution brain electromagnetic tomography (sLORETA), phase-locking value (PLV), and complex network. We investigated the brain functional network triggered by PC7 stimulation by comparing with resting state and non-acupoint stimulation. The results showed that the PC7 stimulation mainly activated frontal lobe and temporal lobe including prefrontal cortex (BA10), insular lobe (BA13), temporal gyrus (BA22), anterior cingulate cortex (BA32), temporal pole (BA38), dorsolateral prefrontal cortex (BA46), and inferior frontal cortex (BA47), which are all closely linked to cognition, spirit, and emotion in brain. Furthermore, the degrees of node in frontal, temporal, and whole brain are increased significantly or extreme significantly with p < 0.05, p < 0.05, and p < 0.01, respectively; clustering coefficient in frontal, temporal, and whole brain are all statistically significant (p < 0.05). The information transmission efficiency of cerebral cortex has been greatly improved. During PC7 stimulation, the topological changes in the activation of cerebral regions and cortical functional networks are consistent with the therapeutic effect, which may provide theoretical support for acupoint stimulation to regulate nerve function.

Evaluating the efficacy and safety of transdermal electrical stimulation on the visual functions of patients with retinitis pigmentosa: a clinical trial protocol for a prospective, multicentre, randomised, double-masked and sham-controlled design (ePICO trial)

IntroductionPreviously, we conducted a clinical trial to evaluate the safety and efficacy of transdermal electrical stimulation (TdES) with skin electrodes to improve the visual functions in patients with retinitis pigmentosa...

Evaluation of Efficacy and Safety of Transdermal Electrical Stimulation in Treatment of Knee Osteoarthritis

Objective:To systematically evaluate the efficacy and safety of transdermal electrical stimulation(TES)in the treatment of knee osteoarthritis(KOA).Methods:A computerized systematic search of randomized controlled trials published in CNKI,Wanfang,VIP,Embase,PubMed,CBM,Cochrane libraries on the treatment of KOA by TES prior to October 2019.Literature data were extracted and reviewed independently by two reviewers,quality evaluation was conducted following the Cochrane collaborative standards,and Meta-analysis was performed using RevMan 5.3 software.Results:According to the inclusion criteria,6 randomized controlled trials with a total of 991 patients were included,including 502 in the experimental group and 489 in the control group,with a ratio of 1∶1.Meta-analysis results showed that the overall effective rate[RR=0.08,95%CI(0.01,0.61),P=0.02],visual analogue pain(VAS)score[MD=1.47,95%CI(1.16,1.77),P<0.001]and incidence of adverse reactions[RR=0.08,95%CI(0.01,0.61),P=0.02]in the experimental group were significantly better than those in the control group.Lysholm knee function evaluation function score scale[MD=3.71,95%CI(-1.59,9.01),P=0.17]showed no significant difference between the two groups.Conclusion:Transdermal electrical stimulation has significant advantages in the treatment of KOA,which can effectively reduce joint pain,improve joint function and quality of life.

Prevention of Intra-abdominal Adhesions by Electrical Stimulation.

The study investigated the ability of transdermal electric stimulation to prevent the formation of intra-abdominal adhesions in the combination with Seprafilm® (anti-adhesive agent). One hundred and twenty-eight (128) rabbits were subjected to a surgical procedure to simulate the adhesion processes. After the simulation, the animals were divided into 4 groups (32 animals each), depending on the application of the methods of prevention: (1) control group (no anti-adhesives or electro-stimulation) (CG); (2) comparison group (applications of Seprafilm®) (SF); (3) comparison group 2 (transdermal electric stimulation of the abdominal muscles) TES; (4) group (transdermal electric stimulation + Seprafilm®) (TES + SF). We observed that the application of the Seprafilm® alone led to a significant decrease in the adhesive process compared to the control group (CG) (p < 0.01). The adhesion process in the group underwent transdermal electrical stimulation (TES) was significantly lower compared to the Seprafilm® group (SF) (p ≤ 0.05). The results demonstrated a significant decrease in the adhesion processes in the SF + TES group on days 1, 3, 7 and 14 in comparison with the CG group (p = 0.001), SF group (p = 0.001) and TES group (p = 0.01) group of animals. This study showed the efficacy of transdermal electrical muscle stimulation for the prevention of intra-abdominal adhesions. Moreover, the combination of Seprafilm® anti-adhesion agent and electrical muscle stimulation resulted in the complete absence of adhesions. Our findings indicate the potential of such strategy for further clinical application.

The influence of vestibular stimulation on metabolism and body composition.

Obesity, diabetes and metabolic disease represent an ongoing and rapidly worsening public health issue in both the developed, and much of the developing world. Although there are many factors that influence fat storage, it has been clearly demonstrated that the homeostatic cornerstone of metabolism lies within the hypothalamus. Moreover, neuronal damage to vital areas of the hypothalamus can drive reregulation or dysregulation of endocrine function, energy expenditure and appetite, thereby promoting a shift in overall metabolic function towards a state of obesity. Therefore, identification of treatments that influence the hypothalamus to improve obesity and associated metabolic diseases has long been a medical goal. Interestingly, evidence from animal studies suggests that activating the vestibular system, specifically the macular gravity receptor, influences the hypothalamus in a way that decreases body fat storage and causes a metabolic shift towards a leaner state. Given that the macular element of the vestibular system has been shown to activate with transdermal electrical stimulation applied to the mastoids, this may be a potential therapeutic approach for obesity, diabetes or related metabolic diseases, whereby repetitive stimulation of the vestibular system influences hypothalamic control of metabolic homeostasis, thereby encouraging decreased fat storage. Here, we present an up-to-date review of the current literature surrounding the vestibular influence of the hypothalamus and associated homeostatic sites in the context of current and novel therapeutic approaches for improved clinical management of obesity and diabetes.

Clinical Trial to Evaluate Safety and Efficacy of Transdermal Electrical Stimulation on Visual Functions of Patients with Retinitis Pigmentosa

To evaluate the safety and efficacy of transdermal electrical stimulation (TdES) with skin electrodes on improving the visual functions of patients with retinitis pigmentosa (RP), twenty eyes of 10 patients with RP underwent TdES (10-ms biphasic pulses, 20 Hz, 30 min) 6 times at 2 week intervals. All patients were stimulated bilaterally with 1.0 mA pulses. The primary endpoint was safety, and the secondary endpoints were the changes in the best-corrected visual acuity (BCVA), visual fields determined by the Humphrey field analyzer (HFA) 10-2 and Goldmann perimetry, and answers to the Visual Function Questionnaire-25. All of the 10 enrolled patients completed the study according to the protocol. No adverse events related to the treatments were reported during the follow-up examinations. The mean BCVA and Early Treatment Diabetic Retinopathy Study visual acuity were significantly improved after the TdES (P = 0.0078 and P = 0.001, respectively). The mean deviation of the HFA 10-2 was also significantly improved (P = 0.0076). We conclude that TdES with skin electrode is a safe therapeutic option and should be considered as a treatment option for patients with RP.

Abstract P387: Sub-Perception Transdermal Vagal Stimulation in Postural Tachycardia Syndrome

Postural Tachycardia Syndrome (POTS) is a clinical syndrome characterized by an excessive increase in heart rate (&gt;= 30 bpm) on standing in the absence of orthostatic hypotension, and frequent orthostatic symptoms for more than 6 months. While most researchers focus on the hyperadrenergic features of POTS, these patients also have significant cardio-vagal (parasympathetic) impairment. We tested the hypothesis that transdermal electrical stimulation of the auricular branch of the vagus nerve will enhance cardio-vagal modulation, reduce heart rate, upright symptoms, and improve orthostatic tolerance. We studied 14 patients with POTS (31.5+/-11.7 years, BMI 22.6+/-3.9 kg/m 2 ). Sham or sub-perception threshold transdermal electrical vagal stimulation was applied in random order to the auricular branch in the right ear in supine and during graded tilt maneuver. Patients with low vagal modulation (low high frequency HF &lt; 200 ms 2 ) responded to vagal stimulation (Kruskal Wallis p=0.01, n=7, Fig left) with significant increase in HF power (eg @50Hz: +51+/-10 ms 2 , p=0.0032). Vagal stimulation during upright tilt tended to reduce orthostatic tachycardia and overall orthostatic symptom score. It improved significantly tilt time (+5.3+/-2.6 min, p=0.0156, Fig right). Patients with higher baseline vagal modulation (HF &gt;= 200 ms 2 ) did not respond to vagal stimulation (interaction p=0.41). This proof of concept study indicates that auricular transdermal vagal stimulation improves supine cardio-vagal function in POTS patients with low vagal modulation. Further research will determine if this approach can be used therapeutically, alone or in combination with other therapies.

Time course of copeptin during a model of experimental pain and hyperalgesia: A randomised volunteer crossover trial.

A reliable biomarker for quantifying pain or hyperalgesia has yet to be found. A surrogate marker of arginine vasopressin, copeptin, is elevated in a number of states of physiological and psychological stress and may have a role in quantifying pain and/or hyperalgesia. To evaluate copeptin as a biomarker for pain or hyperalgesia developing after 120 min of sustained electrical stimulation. Secondary analysis of a randomised, double-blinded, crossover trial. Single, tertiary university hospital from September 2014 to January 2015. A total of 16 healthy, opioid-naïve white men with no confounding medication or history of pain. Copeptin and cortisol were measured five times during an established model of transdermal electrical stimulation designed to assess pain and hyperalgesia. The primary outcome was the change in copeptin concentration after 120 min of sustained electrical stimulation. Secondary outcomes were copeptin and cortisol concentrations after a subsequent period of rest and analyses of copeptin and cortisol concentrations were made in high-dose and low-dose fentanyl groups separately. Total copeptin concentrations were not significantly elevated after 120 min [9.15 pmol l (interquartile ranges (IQR), 3.45 to 35.45 pmol l); P = 0.150] compared with baseline [6.15 pmol l (IQR, 3.60 to 10.62 pmol l)]. In the high-dose fentanyl group, there was a significant increase in copeptin within individuals [P = 0.001; median, 37.9 pmol l (IQR, 8.1 to 62 pmol l)] after 120 min, and in the low-dose fentanyl group a significant decrease in copeptin concentrations within individuals [P = 0.006; median, 4.7 pmol l (IQR, 3.13 to 9.35 pmol l)]. No correlation between copeptin concentration and either the area under the pain curve or area under the hyperalgesia curve could be found, indicating that the observed differences may be due to other fentanyl-mediated effects. Copeptin concentrations do not appear to be associated directly with pain and hyperalgesia. Instead, some fentanyl-mediated effect or effects appear to have greatly increased copeptin concentrations from baseline to 120 min. Clinicaltrials.gov identifier: NCT02252458.

The effectiveness of transdermal electrical stimulation used to treat neuropathic and metabolic disorders in the patients with diabetes mellitus

World-wide occurrence of diabetes mellitus and its complications in the form of neuropathic and metabolic disorders implies the necessity of development and application of the new methods for their combined treatment, such as the low-frequency transdermal electrical stimulation with the use of the OMRON Е-4 myostimulator. This technique was shown to significantly alleviate the symptoms of pain syndrome and other neuropathic manifestations. Moreover, it facilitated the reduction of body weight and visceral fat content in such patients and thereby considerably decreased the risk of development of diabetic complications.

Synchronous Electrical Stimulation of Laryngeal Muscles: An Alternative for Enhancing Recovery of Unilateral Recurrent Laryngeal Nerve Paralysis

Although electrical stimulation of the larynx has been widely studied for treating voice disorders, its effectiveness has not been assessed under safety and comfortable conditions. This article describes design, theoretical issues, and preliminary evaluation of an innovative system for transdermal electrical stimulation of the larynx. The proposed design includes synchronization of electrical stimuli with laryngeal neuromuscular activity. To study whether synchronous electrical stimulation of the larynx could be helpful for improving voice quality in patients with dysphonia due to unilateral recurrent laryngeal nerve paralysis (URLNP). A 3-year prospective study was carried out at the Instituto Nacional de Rehabilitacion in the Mexico City. Ten patients were subjected to transdermal current electrical stimulation synchronized with the fundamental frequency of the vibration of the vocal folds during phonation. The stimulation was triggered during the phase of maximum glottal occlusion. A complete acoustic voice analysis was performed before and after the period of electrical stimulation. Acoustic analysis revealed significant improvements in all parameters after the stimulation period. Transdermal synchronous electrical stimulation of vocal folds seems to be a safe and reliable procedure for enhancing voice quality in patients with (URLNP).

Prospective Clinical Study of a New Implantable Peripheral Nerve Stimulation Device to Treat Chronic Pain

To evaluate clinical use of the StimRouter, an investigational implanted peripheral nerve stimulator for treating chronic neuropathic pain, using the median nerve as a model for that general application. Eight patients with carpal tunnel syndrome and chronic pain despite both carpal tunnel release and treatment with oral pain medications were enrolled in a single-center, open-label trial after institutional review board approval. Primary endpoints were successful implantation near the target peripheral nerve and safety. All 8 patients were implanted temporarily at the median nerve in at least one arm and 2 patients were implanted bilaterally, with 10 implants total. Each implant was considered a separate "patient." For 5 days, all patients received 6 hours of daily transdermal electrical stimulation targeting the median nerve. Pain was measured at baseline, during implant, and after explant. Two patients experienced clinically meaningful (>or=30%) pain reduction throughout the entire 5-day treatment period. Apparent carryover effect in pain reduction also was observed after daily stimulation. After explant, pain returned to baseline, increasing 36.8% to 45.6% relative to average reduced pain with daily stimulation. No significant or unexpected adverse events occurred. Mean patient study satisfaction was 96%, and 100% of patients indicated a preference for permanent implant. Temporary implant of the StimRouter device resulted in both pain reduction and reduced use of oral opioid pain medication during the 5-day stimulation period. The results suggest that permanent implant of the StimRouter System may be safe and effective for treating chronic peripheral neuropathic pain.

Central origin of secondary mechanical hyperalgesia.

The contribution for the development of secondary mechanical hyperalgesia by peripheral mechanisms has not been fully elucidated. We have reevaluated the effects of local anesthetics on electrically evoked flare reaction and mechanical hyperalgesia in human skin. We applied 2% lidocaine via intradermal microdialysis fibers at a length of 10 cm for 110 min to the volar forearm to establish a narrow and stable "anesthetic strip." After 60 min of lidocaine perfusion, transdermal electrical stimulation (1 Hz, 50 mA) was applied at a distance of 1 cm from the microdialysis fibers for 30 min. The areas of allodynia and punctate hyperalgesia were marked at the end of the stimulation period. The flare reaction was assessed by laser Doppler scanner and infrared thermography. Total protein content of the dialysate collected at the stimulating electrode was measured photometrically. We found no increase in protein content during electrical stimulation. Flare area (12.4 +/- 2.3 vs. 3.5 +/- 1.2 cm2) and intensity (426 +/- 24 vs. 257 +/- 21 PU) were significantly reduced beyond the lidocaine strip. The mean temperature increase in the area beyond the lidocaine strip was significantly reduced (1.1 +/- 0.1 vs. 0.2 +/- 0.1 degrees C) and did not differ from control areas. In contrast, allodynia (7.4 +/- 0.7 and 8.6 +/- 0.9 cm) and punctate hyperalgesia (7.6 +/- 0.7 and 8.6 +/- 0.9 cm) developed symmetrically on both sides of the anesthetic strip. Allodynia subsided 4 min after the end of the electrical stimulation. We conclude that the development of allodynia and punctate hyperalgesia in human skin is centrally mediated, whereas the axon reflex vasodilation is of peripheral origin.