Optimized Tibial Nerve Stimulation Partially Reduces Visceral Hypersensitivity in Rats Mediated via Autonomic and Opioid Mechanisms

ObjectivesThe aim of this study was to investigate the therapeutic effect and possible mechanisms of tibial nerve stimulation (TNS) on visceral hypersensitivity in rats.Materials and Methods1) The effects of TNS with five sets of parameters on visceral sensitivity in normal rats were evaluated by the assessment of abdominal electromyogram (EMG) and abdominal withdrawal reflex (AWR). 2) The effects and mechanisms of TNS with a special set of parameters (14 Hz, 330 μsec, and 40% motor threshold) were evaluated in acute visceral hypersensitivity rats induced by restraint stress and colonic hypersensitized rats induced by acetic acid during the neonatal stage assessed by the EMG, AWR, and the spectral analysis of heart rate variability derived from the electrocardiogram.Results1) In normal rats, TNS did not show any effect on the visceromotor reflex. 2) In rats with restraint stress-induced hypersensitivity, TNS with the special set of parameters reduced AWR scores and EMG responses to rectal distention at a pressure of 20–60 mmHg (p < 0.05, vs. baseline for both AWR and EMG). Concurrently, TNS increased vagal activity and decreased sympathetic activity (p < 0.03 for both). 3) Similar effects were noted on the EMG (p < 0.05, vs. baseline) and AWR (p < 0.05 vs. baseline) with acute and chronic TNS in rats with chronic colonic hypersensitivity and the effects were blocked by naloxone.ConclusionsTNS with parameters of 14 Hz, 330 μsec, and 40% motor threshold is effective in improving visceral hypersensitivity in rodent models of colonic hypersensitivity via the modulation of autonomic and opioid mechanisms.     

Transcutaneous Tibial Nerve Stimulation in the Management of Overactive Bladder: A Scoping Review

ObjectiveOveractive bladder (OAB) is a condition that has physical, social, psychosocial, and financial impacts. Transcutaneous tibial nerve stimulation (TTNS) is a modality that stimulates the nerve root fibers of L5-S3, the same spinal segments of the parasympathetic nervous system as the bladder. This scoping review aims to identify current literature available on the feasibility and outcomes of TTNS as a first-line treatment option for OAB.Materials and MethodsA scoping review of six electronic data bases was performed to identify full-text articles from 2015 that explored the impact of TTNS on OAB and bladder dysfunction in people aged >18 years.ResultsA total of 15 articles met the inclusion criteria. TTNS was compared with sham treatment, parasacral stimulation, pelvic floor muscle training (PFMT), anticholinergic medication, and percutaneous tibial nerve stimulation (PTNS). Heterogeneity in treatment application and parameters existed, with variations in treatment duration, frequency of use, and treatment settings such as pulse width (μs) and frequency (Hz). Results indicated that TTNS has efficacy equal to PFMT and PTNS in the management of OAB; however, it is not as efficacious as anticholinergic medication.ConclusionsTTNS is a promising first-line management option for people with OAB, particularly in the older population and for those with neurogenic bladder. It can provide symptomatic relief from urinary incontinence, frequency, urgency, and nocturia, while avoiding the bothersome side effects of more invasive or pharmaceutical therapies. Heterogeneity in treatment parameters limits generalizability and translation of the most appropriate clinical application and should be considered in future trials.     

Analgesic Effects of Tonic and Burst Dorsal Root Ganglion Stimulation in Rats With Painful Tibial Nerve Injury

ObjectivesDorsal root ganglion (DRG) stimulation is effective in treating chronic pain. While burst stimulation has been proven to enhance the therapeutic efficacy in spinal cord stimulation, currently only a tonic stimulation waveform is clinically used in DRG stimulation. We hypothesized that burst DRG stimulation might also produce analgesic effect in a preclinical neuropathic pain model. We evaluated both the therapeutic effects of burst DRG stimulation and the possible effects of DRG stimulation upon inflammation within the DRG in a preclinical neuropathic pain model.Materials and MethodsRats received either a painful tibial nerve injury or sham surgery. Analgesic effects of DRG stimulation were evaluated by testing a battery of evoked pain-related behaviors as well as measuring the positive affective state associated with relief of spontaneous pain using conditioned place preference. Histological evidence for neuronal trauma or neuroinflammation was evaluated.ResultsAll of the waveforms tested (20 Hz-tonic, 20 Hz-burst, and 40 Hz-burst) have similar analgesic effects in sensory tests and conditioned place preference. Long-term DRG stimulation for two weeks does not change DRG expression of markers for nerve injury and neuroinflammation.ConclusionsDRG stimulation using burst waveform might be also suitable for treating neuropathic pain.     

Efficacy and Effectiveness of Percutaneous Tibial Nerve Stimulation in the Treatment of Pelvic Organ Disorders: A Systematic Review

Objective: This systematic review aimed to determine the efficacy and effectiveness of percutaneous tibial nerve stimulation (PTNS) on symptoms of overactive bladder (OAB) and pelvic organ disorders, pain, adverse events (AEs), and quality of life (QoL). Methods: A literature search was performed in September 2011 in the databases MEDLINE, CINAHL, and EMBASE. Hand searching of references was conducted. Only randomized controlled trials (RCTs) and controlled clinical trials (CCTs) with adult patients were included. Results: Seven studies met the eligibility criteria. Five RCTs indicated improvement (range 36.7–80%) on OAB symptoms, frequency, urgency, nocturia, and incontinence. One CCT reported improvement (mean 15.7) in 53% of the subjects on fecal incontinence (FI) symptoms on an FI Questionnaire (range 0–20). One RCT showed more than 50% improvement on pain (40%) and symptom scores (66.6%) in chronic pelvic pain (CPP). Limitations are the small amount, overall low quality, and variety in outcome measures of included studies. Only minor AEs were reported. No meta‐analysis was performed as a consequence of heterogeneous data. Conclusions: This systematic review provides evidence for the efficacy of PTNS on symptoms, pain, and QoL measures of OAB, FI and category IIIB CP/CPP. Evidence of effectiveness was found on symptoms and QoL for OAB. The total amount of seven included studies, from which even the most favorable study has some potential bias, is too small to draw firm conclusions. Independent high quality RCTs are necessary to confirm and delineate the range of therapeutic effects of PTNS in this region. PTNS is a safe intervention.     

Adult Retinofugal Axons Regenerating Through Peripheral Nerve Grafts Can Restore the Light-induced Pupilloconstriction Reflex

To investigate the ability of mature regenerating retinal axons to form functional connections within central targets, severed axons were guided into the primary visual centres which subserve the pupillary constriction reflex in response to light. The ocular stump of the transected optic nerve of adult rats was connected by means of an autologous peripheral nerve graft with the pretectal region which contains the relay nucleus of pupillary constriction, the olivary pretectal nucleus. This nucleus is efferently connected with preganglionic neurons in the oculomotor nuclear complex which innervates parasympathetically the muscle constrictors of the iris. Six to sixteen weeks after optic nerve transection and peripheral nerve transplantation, brisk responses were observed in the pupils upon illumination of the transplanted eye. Recovery of the pupil responses indicated that retinal neurons used the peripheral nerve 'bridge' to access the pretectum, in which they established synaptic contacts in sufficient density and with appropriate specificity to reconstitute the function of the traumatically interrupted neuronal circuitry.     

Effects of 10-kHz Subthreshold Stimulation on Human Peripheral Nerve Activation

ObjectiveThe mechanisms of action of high-frequency stimulation (HFS) are unknown. We investigated the possible mechanism of subthreshold superexcitability of HFS on the excitability of the peripheral nerve.Materials and MethodsThe ulnar nerve was stimulated at the wrist in six healthy participants with a single (control) stimulus, and the responses were compared with the responses to a continuous train of 5 seconds at frequencies of 500 Hz, 2.5 kHz, 5 kHz, and 10 kHz. Threshold intensity for compound muscle action potential (CMAP) was defined as intensity producing a 100-μV amplitude in ten sequential trials and “subthreshold” as 10% below the CMAP threshold. HFS threshold was defined as stimulation intensity eliciting visible tetanic contraction.ResultsComparing the threshold of single pulse stimulation for eliciting CMAP vs threshold for HFS response and pooling data at different frequencies (500 Hz–10 kHz) revealed a significant difference (p = 0.00015). This difference was most obvious at 10 kHz, with a mean value for threshold reduction of 42.2%.ConclusionsHFS with a stimulation intensity below the threshold for a single pulse induces axonal superexcitability if applied in a train. It can activate the peripheral nerve and produce a tetanic muscle response. Subthreshold superexcitability may allow new insights into the mechanism of HFS.     

迷走神经刺激对癫癎大鼠行为及脑电图的影响

目的 :观察颈部迷走神经干电刺激对癫大鼠行为及额叶、海马、杏仁核脑区放电的影响 ,为迷走神经刺激 (VagusNerveStimulation ,VNS)抑机制研究提供理论依据。方法 :利用脑立体定位手段 ,将电极埋入大鼠脑部双侧额叶皮质、海马和杏仁核 ,记录VNS前后由红藻氨酸 (KA)诱发复杂部分性癫大鼠脑电变化并观察动物行为的改变。结果 :VNS后大鼠癫强直 阵挛发作次数明显减少 ,首次发作潜伏期延长 ,癫发作平均持续时间缩短 ;VNS尤其对杏仁核放电有明显的抑制作用。结论 :VNS能有效抑制KA诱发的复杂部分性癫发作 ,并且杏仁核可能是抑作用的关键核团     

Soleus Stretch Reflex Inhibition in the Early Swing Phase of Gait Using Deep Peroneal Nerve Stimulation in Spastic Stroke Participants

Objectives. To investigate the feasibility of inhibiting the stretch reflex of the soleus muscle by a conditioning stimulus applied to the deep peroneal nerve in spastic stroke participants during the early swing phase of gait. Materials and Methods. This study investigated the effect of an electrical conditioning stimulus applied to the deep peroneal nerve on the magnitude at the peak of the soleus stretch reflex in the early swing phase of gait in six spastic stroke participants. Results. Five of the six participants showed a reduced stretch reflex of more than 80%. On average (n= 4), it was shown that maximal inhibition occurred at a conditioning‐test interval of 114 ms and had a magnitude of more than 90% (p < 0.05). For all five participants investigated, there was a significant reduction in the sensitivity of the soleus stretch reflex after conditioning (p < 0.02). Conclusions. It is concluded that the inhibition of the soleus stretch reflex with an electrical conditioning stimulus applied to the deep peroneal nerve is feasible in the early swing phase of walking. This shows a potential for being used in the rehabilitation of walking by spastic stroke persons.     

Implant‐Driven Tibial Nerve Stimulation in the Treatment of Refractory Overactive Bladder Syndrome: 12‐Month Follow‐up

Objectives. To investigate feasibility and safety of implant‐driven tibial nerve stimulation. Materials and Methods. Eight patients with refractory overactive bladder were successfully treated with implanted percutaneous tibial nerve stimulation (PTNS). Patients were evaluated with bladder diaries, quality of life questionnaires, and physical examination before implantation, and at 3, 6, and 12 months of follow‐up. The primary objective was ≥ 50% reduction of the number of incontinence episodes and/or voids on bladder diary. The Wilcoxon signed ranks test was used. Results. At 3, 6 and 12 months, respectively five, six, and four patients met the primary objective. At 3‐ and 6‐month follow‐up, voiding and quality of life parameters had significantly (p < 0.05) improved. Urinary tract infection, temporarily walking difficulties, and spontaneous radiating sensations were reported as adverse events and no local infection, erosion, or dislocation. Conclusions. Implant‐driven tibial nerve stimulation seems to be feasible and safe.     

Electrophysiological Studies of Cervical Vagus Nerve Stimulation in Humans: I. EEG Effects

Evidence from studies of experimental animals indicates that electrical stimulation of the vagus nerve alters EEGs under certain stimulus parameters. We report EEG effects of electrical stimulation of the vagus nerve in 9 patients with medically intractable seizures as part of a clinical trial of chronic vagal stimulation for control of epilepsy. The mechanism of action of the vagal antiepileptic effect is unknown, and we believed that analysis of electrophysiologic effects of vagal nerve stimulation would help elucidate the brain areas affected. The left vagus nerve in the neck was stimulated with a programmable implanted stimulator. Stimulation at various stimulus frequencies and amplitudes had no noticeable effect on EEG activity whether the patient was under general anesthesia, awake, or asleep, but vagus nerve stimulation may interrupt ongoing ictal EEG activity.