Trigeminal Stimulation Research Articles

Outpatient Approach to Resistant and Refractory Migraine in Children and Adolescents: a Narrative Review.

Migraine is one of the top reasons for consulting a pediatric neurologist. Although the majority of children and adolescents who receive evidence-based first-line interventions for migraine will improve substantially, a subset of patients develop resistant or refractory migraine. In this review, we summarize the level of evidence for a variety of acute and preventive treatment options to consider in children and adolescents with resistant or refractory migraine. We describe the level of evidence for interventional procedures (onabotulinumtoxinA injections, greater occipital and other nerve blocks), neuromodulation (single-pulse transcranial magnetic stimulation, external trigeminal nerve stimulation, remote electrical neuromodulation, and non-invasive vagal nerve stimulation), calcitonin gene-related peptide (CGRP) pathway antagonists (anti-CGRP monoclonal antibodies and gepants), psychological therapies, and manual therapies (acupuncture, craniosacral therapy, massage and physical therapy, and spinal manipulation).

New Trigeminal Stimulation Technique with Dorsal Root Ganglion Stimulation Electrode and Maxillary Fixation: Technique Description.

Trigeminal neuralgia is considered the worst pain a human being can experience. Initial treatment uses anticonvulsant sodium channel blockers, which relieve pain in approximately 70% of patients. In refractory cases, it is possible to perform ablative treatments, decompressive surgeries, and neuromodulatory techniques. This report describes the treatment of a patient with refractory trigeminal neuralgia who continued to have a painful clinical presentation after four surgical procedures and three ablative procedures. The patient presented with severe pain (verbal numerical scale between 9 and 10), manifesting an evident suicidal ideation. A dorsal root ganglion (DRG) stimulation electrode was implanted in the trigeminal ganglion through intraoral puncture with maxillary fixation of the electrode, in order to minimize the chances of displacement. The test phase consisted of implanting a quadripolar electrode for DRG stimulation through puncture lateral to the buccal rim in a fluoroscopic coaxial view. The electrode was fixed to the skin and maintained for 5days, during which the patient remained completely painfree. After the 5-day test period, the definitive stimulation electrode was implanted, this time with intraoral puncture and maxillary electrode fixation. The patient remains pain free in the 3-month follow-up, with no displacement of the electrode. The DRG electrode may be considered a therapeutic option in patients with severe trigeminal neuralgia. Controlled studies must be performed to determine the efficacy and safety of the method.

Migraine treatment with external concurrent occipital and trigeminal neurostimulation-A randomized controlled trial.

To evaluate the efficacy and safety of concurrent non-invasive stimulation of occipital and trigeminal nerves in acute treatment of migraine with or without aura. Non-invasive neuromodulation devices stimulating a single peripheral nerve or anatomic distribution are routinely used by patients with migraine refractory to the first-line drugs or those who opt out of pharmaceutical treatment. Concurrent occipital and trigeminal stimulation was described in an invasive setting, and its safety cost outweighed its efficacy gain. This study evaluated the efficacy and safety of an external concurrent occipital and trigeminal device in acute treatment of migraine. This was a randomized, sham-controlled, double-blind, multi-center trial. Patients 18 years of age or older who met the International Classification of Headache Disorders (2018) diagnostic criteria for migraine with or without aura, reported 1-6 migraine attacks per month, and other headaches no more than 6 days per month were enrolled. Of 131 intention-to-treat participants (67 and 64 in the active and sham groups, respectively), 109 (50 and 59 in the active and sham groups, respectively) treated at least one migraine episode. Reduction of migraine headache (pain relief) 2 h after treatment initiation was the primary efficacy endpoint. Pain relief at 1 h, and pain freedom and relief in most bothersome symptom at 2 h after treatment initiation were the secondary endpoints. Freedom from most bothersome symptom at 2 h and sustained pain freedom 24 h after treatment initiation were among the exploratory endpoints. Sixty percent of participants (30/50) in the active arm reported pain relief at 2 h after initiation of the first eligible treatment (primary outcome) compared to 37% (22/59) in the control arm (difference, 23%; 95% confidence interval [CI], 2%-41%; p=0.018). Pain freedom at 2 h without rescue medication was reported by 46% (23/50) of participants in the active arm and by 12% (7/59) of participants in the sham arm (p < 0.001). Pain freedom 2 h after the treatment and, subsequently, at 24 h, was reported by 4.25 times more participants in the active arm (36%; 18/50) than in the sham arm (8%; 5/59). The 28% difference was statistically significant (95% CI, 1%-43%; p < 0.001). A 4.25-fold difference was also observed comparing the proportion of participants free from pain and most bothersome symptom 2 h after the stimulation (47% [17/36] and 11% [5/45] in the active and sham arms, respectively; 95% CI, 14%-54%; p < 0.001). Adverse events were not serious or severe. All study-related events resolved without treatment. External concurrent occipital and trigeminal neurostimulation is a well-tolerated, safe, and effective migraine treatment that provided a fast and durable relief and freedom from migraine pain and associated symptoms in a randomized setting. The observed safety and performance suggest external concurrent occipital and trigeminal neurostimulation is a viable alternative to the currently available acute migraine treatments. clinicaltrials.gov identifier NCT03631550.

Application of Neuroscience Tools in Building Construction - An Interdisciplinary Analysis.

Interdisciplinary integration is a new driving force in development of science and technology. Neuroscience, a powerful tool for studying human physiology and psychology that is greatly interconnected with the field of building construction, has attracted numerous research attention. In this paper, we systematically review the interdisciplinary applications of neuroscience tools using bibliometric methods. We report that the built environment, construction safety, architectural design, and occupational health are the main areas of research attention, while thermal comfort, air quality, hazard recognition, safety training, aesthetic design, and biophilic design, among others, comprise the most frequently studied topics with regards to application of neuroscience tools. Currently, eye tracking and the electroencephalogram are the most commonly used tools in the field of building construction, while functional near-infrared spectroscopy, functional magnetic resonance imaging and trigeminal nerve stimulation are still at their initial stage of application.

Effects of trigeminal nerve stimulation on parameters derived from pulse wave analysis in young healthy subjects.

Studies on trigeminal nerve stimulation (TNS) by facial cooling (FC) could give an insight to physiological mechanisms of cardiovascular response to activation of both parasympathetic and sympathetic nervous systems. We hypothesised that trigeminal nerve stimulation would positively influence on the factors which increase left ventricle work. The aim of the present study was to investigate hemodynamic changes assessed by pulse wave analysis (PWA) in the very early phase of this reflex. In 15 young (aged 20.3±1.3 y/o; mean ±SD) healthy individuals (10 males) PWA was performed before and after 30 seconds of FC. TNS caused decrease in heart rate (76.8±9.4 bpm vs 66.6±9.8 bpm; p=0.0038; mean ±SD) and increase in peripheral diastolic blood pressure (68±5.9 mmHg vs. 70.9±8.6 mmHg; p=0.028; mean ±SD) and no changes in other blood pressure values (peripheral and central), nor augmentation index were observed. PWA showed decrease in time of the peak pressure of left ventricle contraction (107.6±15.9 ms vs. 100.2±12.06 ms; p=0.027; mean ±SD), increase in time of the peak pressure of the reflected wave return (cT2, 187±28.03 ms vs 198.6±27.9 ms; p=0.028; mean ±SD) and increase in the difference between cT2 and time of the beginning of the reflected wave return (43.3±18.7 ms vs. 59.7 vs. 59.7±20.99 ms; p=0.0076; mean ±SD). We conclude that in the early phase of response to TNS, there is an increase in contractility of left ventricle and aortic compliance, as well as increase in peripheral vascular resistance and pressure load of returning pulse wave occurs.

Effects of lung volume and trigeminal nerve stimulation on diving response in breath-hold divers and non-divers

PurposeThis study investigated the effects of lung volume and trigeminal nerve stimulation (TS) on diving responses in breath-hold divers (BHDs) and non-divers (NDs). MethodsEight BHDs and nine NDs performed four breath-hold trials at different lung volumes, with or without TS, and one trial of TS. Haemodynamic parameters and electrocardiograms were measured for each trial. ResultsDuring the TS trial, the total peripheral resistance increased more in BHDs. Breath-hold performed at total lung capacity showed a more pronounced decrease in stroke volume and cardiac output in BHDs. The decrease in heart rate and increase in total peripheral resistance were more pronounced in BHDs when breath-holding was performed with TS. ConclusionThe more pronounced diving response in BHDs was attributed to the greater increase in total peripheral resistance caused by TS. Furthermore, the lower stroke volume and cardiac output in BH performed at total lung capacity could also cause a more pronounced diving response in BHDs.

Electrical stimulation of the trigeminal nerve improves olfaction in healthy individuals: A randomized, double-blind, sham-controlled trial

BackgroundBoth activated by environmental odorants, there is a clear role for the intranasal trigeminal and olfactory nerves in smell function. Unfortunately, our ability to perceive odorants decreases with age or with injury, and limited interventions are available to treat smell loss. ObjectiveWe investigated whether electrical stimulation of the trigeminal nerve via trigeminal nerve stimulation (TNS) or transcranial direct current stimulation (tDCS) modulates odor sensitivity in healthy individuals. MethodsWe recruited 20 healthy adults (12 Female, mean age = 27) to participate in this three-visit, randomized, double-blind, sham-controlled trial. Participants were randomized to receive one of three stimulation modalities (TNS, tDCS, or sham) during each of their visits. Odor detection thresholds were obtained at baseline, immediately post-intervention, and 30-min post-intervention. Furthermore, participants were asked to complete a sustained attention task and mood assessments before odor detection testing. ResultsFindings reveal a timeXcondition interaction for guaiacol (GUA) odorant detection thresholds (F (3.188, 60.57) = 3.833, P = 0.0125), but not phenyl ethyl alcohol (PEA) odorant thresholds. At 30-min post-stimulation, both active TNS and active tDCS showed significantly increased sensitivity to GUA compared to sham TNS (Sham TNS = −8.30% vs. Active TNS = 9.11%, mean difference 17.43%, 95% CI 5.674 to 29.18, p = 0.0044; Sham TNS = −8.30% vs. Active tDCS = 13.58%, mean difference 21.89%, 95% CI 10.47 to 33.32, p = 0.0004). ConclusionTNS is a safe, simple, noninvasive method for boosting olfaction. Future studies should investigate the use of TNS on smell function across different stimulation parameters, odorants, and patient populations.

P 85 Impaired pain processing on a brainstem level in patients with complex regional pain syndrome

Introduction: The complex regional pain syndrome (CRPS) is a chronic pain condition, which can follow limb trauma and is accompanied with sensorimotor dysfunction 1 . Current pathophysiological concepts assume local inflammatory processes that lead to peripheral and central sensitization of the nociceptive system 2 . Secondary maladaptive alterations of cortical sensorimotor excitability and disinhibition are well-established but little is known about the contribution of the brainstem. Preliminary evidence for altered brainstem excitability to trigeminal afferent stimulation was recently provided 3,4 . This study uses a more comprehensive assessment of the nociceptive blink reflex (NBR) to assess the interaction of brainstem excitability and habituation to painful stimuli. Methods : 14 CRPS patients (10 female, 53 ± 17.6 years) and 10 controls (HCs; 9 female, 52±18.3) received assessments of pain and the NBR (R2 component, 2 trials, 10 stimuli/trial, interstimulus interval 3-5s). The R2 area (R2a) and habituation (R2h; gradient of R2a against stimulus order) were measured for the stimulated/non-stimulated side (_s/_ns). Results : Pain levels were 5,0±1,5/10 at rest and 7,2±2,1/10 during movements. ANOVA revealed a significant group effect for patients vs. controls (F=4.0; p=0.015). Post hoc tests were corrected for multiple comparisons and showed exceeding excitability (R2a_s: t=2.42, p=0.048; R2a_ns: t=2.98, p= 0.028) and impaired habituation (R2h_s: t=2.45, p=0.044; R2h_ns t=2.60, p=0.036). No significant associations of both disease duration and pain levels with NBR measurements could be obtained. Discussion : We here provide first evidence of altered NBR excitability and habituation indicating altered pain processing on a brainstem level. These results complement previous findings by demonstrating disinhibition as a source of increased brainstem excitability to painful stimulation remote from the limb directly affected by CRPS 4 . Future investigations are needed for a better understanding of the brainstem and its role in the pathophysiology of CRPS. The potential of the NBR as clinical biomarker, as it has been demonstrated in other pain diseases, should also be clarified in further investigation 5 . Literature: 1 Veldman PH et al. Signs and symptoms of reflex sympathetic dystrophy: prospective study of 829 patients. Lancet 1993. 2 Eldufani J et al. A medical mystery of CRPS. Heliyon. 2020. 3 Thiele A, et al. Treatment with calcitonin gene-related peptide antibodies modifies brainstem excitability and habituation to nociceptive trigeminal stimulation in migraineurs. CEPHALALGIA. 2021. 4 Drummond P et al. The Source of Hemisensory Disturbances in CRPS, The Clinical Journal of Pain: 2021. 5 De Marinis M et al. Decreased habituation of the R2component of the blink reflex in migraine patients. Clinical neurophysiology. 2003.

Trigeminal nerve stimulation for disorders of consciousness

According to previous case reports, trigeminal nerve stimulation (TNS) can be successfully used to wake a non-responsive unconscious patient. However, no studies have comprehensively investigated the effect of TNS on patients with disorders of consciousness (DOC). Therefore, the present study aimed to assess the safety and efficacy of TNS in DOC patients recruited at the First Affiliated Hospital of Nanchang University. We used Coma Recovery Scale-Revised (CRS-R) scores to assess patients at baseline and after 1–4 weeks of TNS. The patients were further followed up for 4 weeks after the last stimulation to evaluate the safety of the procedure. The participant group comprised 21 DOC patients with an acquired brain injury who were more than 3 months post-injury. The participants were 44.29 ± 12.55 years old and 5.52 ± 1.83 months post-DOC onset, and included 12 patients who were in a vegetative state or had unresponsive wakefulness syndrome and 9 patients who were in a minimally conscious state. Compared with CRS-R scores at baseline, those at weeks 4 and 8 showed no significant improvements in any of the DOC patients. Nonetheless, CRS-R scores improved throughout the study period in 8 out of the 21 DOC patients. Among those with improved scores, two patients in a minimally conscious state had improved CRS-R scores at week 4, while five had improved scores at 4 weeks later. Only one patient with vegetative state/unresponsive wakefulness syndrome had recovered to a minimally conscious state at week 4. Importantly, no obvious treatment-related adverse events were considered to be related to TNS. Taken together, these data provide early evidence that TNS may be an effective and safe approach for promoting the recovery of consciousness in patients with neurological disorders.

Neurotherapeutics for ADHD: Do they work?

This paper reflects on the use of neurotherapeutics for attention-deficit/hyperactivity disorder (ADHD). ADHD is the most imaged child psychiatric disorder, with over 3 decades of magnetic resonance imaging (MRI) research. Findings are relatively homogeneous compared to other psychiatric conditions with consistent evidence for differences, albeit small, relative to healthy controls in the structure and function of several frontal, parietotemporal, and striatal brain regions as well as their inter-regional structural and functional connections. The functional deficits have been targeted with modern neurotherapeutics, including neurofeedback (using most commonly electroencephalography and more recently functional near-infrared spectroscopy and functional MRI) and non-invasive brain stimulation (such as repetitive transcranial magnetic stimulation, transcranial direct current stimulation, or external trigeminal nerve stimulation). Except for electroencephalography-neurofeedback, the majority of neurotherapeutic studies have been relatively small, with very heterogenous research protocols and outcome measures and-likely as a consequence-inconsistent findings. Furthermore, most brain stimulation studies have tested effects on cognitive functions rather than clinical symptoms. So far, findings have not been very promising. Future studies require systematic testing of optimal protocols in large samples or homogenous subgroups to understand response prediction that could lead to individualized treatment.

Long latency responses in tongue muscle elicited by various stimulation sites in anesthetized humans – New insights into tongue-related brainstem reflexes

BackgroundLong Latency Responses (LLR) in tongue muscles are a scarcely described phenomenon, the physiology of which is uncertain. ObjectivesThe aim of this exploratory, observational study was to describe tongue-LLR elicited by direct trigeminal nerve (DTNS), dorsal column (DoColS), transcranial electric (TES) and peripheral median nerve (MNS) stimulation in a total of 93 patients undergoing neurosurgical procedures under general anesthesia. MethodsBilateral tongue responses were derived concurrently after each of the following stimulations: (1) DTNS applied with single monophasic or train-of-three pulses, ≤5 mA; (2) DoColS applied with a train-of-three pulses, ≤10 mA; (3) TES consisting of an anodal train-of-five stimulation, ≤250 mA; (4) MNS at wrist consisting of single or train-of-three monophasic pulses, ≤50 mA. Polyphasic tongue muscle responses exceeding the latencies of tongue compound muscle action potentials or motor evoked potentials were classified as LLR. ResultsTongue-LLR were evoked from all stimulation sites, with latencies as follows: (1) DTNS: solely ipsilateral 20.2 ± 3.3 msec; (2) DoColS: ipsilateral 25.9 ± 1.6 msec, contralateral 25.1 ± 4.2 msec; (3) TES: contralateral 55.3 ± 10.2 msec, ipsilateral 54.9 ± 12.0 msec; (4) MNS: ipsilateral 37.8 ± 4.7 msec and contralateral 40.3 ± 3.5 msec. ConclusionThe tongue muscles are a common efferent in brainstem pathways targeted by trigeminal and cervical sensory fibers. DTNS can elicit the “trigemino-hypoglossal-reflex”. For the MNS elicited tongue-LLR, we propose the term “somatosensory-evoked tongue-reflex”. Although the origin of the TES related tongue-LLR remains unclear, these data will help to interpret intraoperative tongue recordings.

Phase 3 randomized, double-blind, sham-controlled Trial of e-TNS for the Acute treatment of Migraine (TEAM)

Migraine is one of the most common and debilitating neurological disorders worldwide. External Trigeminal Nerve Stimulation (e-TNS) is a non-pharmacological, non-invasive therapeutic alternative for patients with migraine. The TEAM study was a prospective, multicenter, randomized, double-blind, sham-controlled, Phase 3 trial for 2-h, continuous, e-TNS treatment of a single moderate or severe migraine attack at home. A total of 538 adults meeting the International Classification of Headache Disorders 3rd edition criteria for 2–8 migraine headache days per month were recruited and randomized in a 1:1 ratio to 2-h active or sham stimulation. Migraine pain levels and most bothersome migraine-associated symptoms (MBS) were recorded at baseline, 2 h, and 24 h using a paper diary. The primary endpoints for the study were pain freedom at 2 h and freedom from the MBS at 2 h. The secondary endpoints were pain relief at 2 h, absence of most bothersome migraine-associated symptoms (MBSs) at 2 h, acute medication use within 24 h after treatment, sustained pain freedom at 24 h, and sustained pain relief at 24 h. Adverse event data was also collected and compared between groups. Five hundred thirty-eight patients were randomized to either the verum (n = 259) or sham (n = 279) group and were included in an intention-to-treat analysis. The percentage of patients with pain freedom at 2 h was 7.2% higher in verum (25.5%) compared to sham (18.3%; p = 0.043). Resolution of most bothersome migraine-associated symptom was 14.1% higher in verum (56.4%) compared to sham (42.3%; p = 0.001). With regards to secondary outcomes, pain relief at 2 h was 14.3% higher in verum (69.5%) than sham (55.2%; p = 0.001), absence of all migraine-associated symptoms at 2 h was 8.4% higher in verum (42.5%) than sham (34.1%; p = 0.044), sustained pain freedom and pain relief at 24 h was 7.0% and 11.5% higher in verum (22.8 and 45.9%) than sham (15.8 and 34.4%; p = 0.039 and .006, respectively). No serious adverse events were reported. Treatment with 2-h e-TNS is a safe and effective, non-invasive, and non-pharmacological alternative for the acute treatment of migraine attacks in an at-home setting.Trial registration Clinicaltrials.gov Identifier: NCT03465904. Registered 14/03/2018. https://www.clinicaltrials.gov/ct2/show/record/NCT03465904.

Теоретичні основи застосування високотехнологічних засобів реабілітації у дітей з церебральним паралічем

The purpose of the study was to substantiate theoretically the need in high-tech rehabilitation tools for children with cerebral palsy, to identify the shortcomings of their use and to determine the role of the equipment in correcting the pathological stereotype of movement. Materials and methods. Methodological approach was used: analysis of literature sources and resources of the Internet (foreign and domestic on the PubMed and Google Scholar platforms), method of system analysis, method of comparison. Results and discussion. One of the main goals in the process of rehabilitation of children with cerebral palsy is to improve motor control and, thus, increase independence, participation and overall quality of life. In the modern world, the use of new methods of exercise therapy using high-tech robotic devices («Lokomat», «Armeo»), as well as new methods of physiotherapy, in particular, translingual electrical stimulation of the brain (TESB) «Brain-port» is becoming relevant for the treatment of children with cerebral palsy. Features and some restrictions of use of the above-stated devices were defined. Exercises on the Lokomat device help to form a motor "stereotype" of physiological walking, as well as strengthen the muscles of the lower extremities, and with the help of biological feedback to increase the motivation to exercise in children. The therapeutic goals of Armeo are to improve or maintain reach, capture and transmission movements, active range of motion by attaching an exoskeleton to the patient's arm. Translingual neurostimulation plays an important role in modulating neuroplastic changes in the brain, provides electrical stimulation of trigeminal and facial cranial nerves that modulate sensorimotor and vestibular functions. The devices help to improve the static and dynamic function of the body, reduce muscle tone, improve joint mobility in children with cerebral palsy. Their use in the process of physical therapy emphasizes the need for individualization of rehabilitation programs. Conclusion. The analysis of literature sources testifies to the effectiveness of the use of high-tech tools in the process of rehabilitation of children with cerebral palsy in combination with traditional methods. It helps to improve motor and cognitive function in children with cerebral palsy by correcting the mechanism of musculoskeletal control. Robotic techniques allow to change the pathological stereotype of movement. The prospect is to study the psychophysiological parameters of children with cerebral palsy during rehabilitation using modern technologies

Ratings of trigeminal stimulation in patients with olfactory loss.

Ratings of trigeminal stimulation in patients with olfactory loss.

Trigeminal Nerve Stimulation Improves Cerebral Macrocirculation and Microcirculation After Subarachnoid Hemorrhage: An Exploratory Study.

Delayed cerebral ischemia (DCI) is the most consequential secondary insult after aneurysmal subarachnoid hemorrhage (SAH). It is a multifactorial process caused by a combination of large artery vasospasm and microcirculatory dysregulation. Despite numerous efforts, no effective therapeutic strategies are available to prevent DCI. The trigeminal nerve richly innervates cerebral blood vessels and releases a host of vasoactive agents upon stimulation. As such, electrical trigeminal nerve stimulation (TNS) has the capability of enhancing cerebral circulation. To determine whether TNS can restore impaired cerebral macrocirculation and microcirculation in an experimental rat model of SAH. The animals were randomly assigned to sham-operated, SAH-control, and SAH-TNS groups. SAH was induced by endovascular perforation on Day 0, followed by KCl-induced cortical spreading depolarization on day 1, and sample collection on day 2. TNS was delivered on day 1. Multiple end points were assessed including cerebral vasospasm, microvascular spasm, microthrombosis, calcitonin gene-related peptide and intercellular adhesion molecule-1 concentrations, degree of cerebral ischemia and apoptosis, and neurobehavioral outcomes. SAH resulted in significant vasoconstriction in both major cerebral vessels and cortical pial arterioles. Compared with the SAH-control group, TNS increased lumen diameters of the internal carotid artery, middle cerebral artery, and anterior cerebral artery, and decreased pial arteriolar wall thickness. Additionally, TNS increased cerebrospinal fluid calcitonin gene-related peptide levels, and decreased cortical intercellular adhesion molecule-1 expression, parenchymal microthrombi formation, ischemia-induced hypoxic injury, cellular apoptosis, and neurobehavioral deficits. Our results suggest that TNS can enhance cerebral circulation at multiple levels, lessen the impact of cerebral ischemia, and ameliorate the consequences of DCI after SAH.

The Effectiveness of Trigeminal Nerve Stimulation on Traumatic Brain Injury

ObjectivesTrigeminal nerve stimulation (TNS) is a promising strategy in treating diseases of the nervous system. In this study, the effects of TNS on traumatic brain injury (TBI) were investigated in a mouse model. Materials and MethodsTBI was induced using a weight-drop device, and TNS treatment was delivered in the first hour after the TBI. Twenty-four hours later, the mice’s behavior, brain edema, and expression of inflammatory factors were tested. Functional magnetic resonance imaging also was used to explore the possible effects of TNS on brain activity. ResultsTNS alleviates TBI-induced neurological dysfunction in animal behavior tests, besides protecting the blood-brain barrier and reducing the level of brain edema. TNS also effectively reduces the level of tumor necrosis factor-α and interleukin 6 and downregulates the cleaved caspase-3 signaling pathway. A series of brain areas was found to be possibly regulated by TNS, thus affecting the neural functions of animals. ConclusionThis study elucidates the role of TNS as an effective treatment for TBI by inhibiting the occurrence of a secondary brain injury.

Vascular responses to simulated breath-hold diving involving multiple reflexes.

Breath-hold diving evokes a complex cardiovascular response. The degrees of hypertension induced by the diving reflex are substantial and accentuated by the underwater swimming. This condition provides a circulatory challenge to properly buffer and cushion cardiac pulsations. We determined hemodynamic changes during the diving maneuver and hypothesized that central artery compliance would be augmented during simulated breath-hold diving. A total of 20 healthy young adults were studied. Hemodynamics were measured during exercise on a cycle ergometer, apnea, face immersion in cold water (trigeminal stimulation), and simulated breath-hold diving. Arterial compliance was measured by recording the carotid artery diameter from images derived from an ultrasound machine at the cephalic portion of the common carotid artery 1-2 cm proximal to the carotid bulb, whereas arterial pressure waveforms were obtained using an arterial tonometry placed on the contralateral carotid artery and recorded on a data acquisition software. The change in diameter was divided by the change in blood pressure to calculate arterial compliance. Arterial compliance increased with simulated diving compared with rest (P = 0.007) and was elevated compared with exercise and apnea alone (P < 0.01). A significant increase in heart rate was observed with exercise, apnea, and facial immersion when compared with rest (P < 0.001). However, simulated diving brought the heart rate down to resting levels. Cardiac output increased with all conditions (P < 0.001), with an attenuated response during simulated diving compared with exercise and facial immersion (P < 0.05). Mean blood pressure was elevated during all conditions (P < 0.001), with a further elevation observed during simulated diving compared with exercise (P < 0.001), apnea (P = 0.016), and facial immersion (P < 0.001). Total peripheral resistance was decreased during exercise and facial immersion compared with rest (P < 0.001) but was increased during simulated diving compared with exercise (P < 0.001), apnea (P = 0.008), and facial immersion (P = 0.003). We concluded that central artery compliance is augmented during simulated breath-hold diving to help buffer cardiac pulsations.

Neuromodulation for Prevention and Treatment of Headache Disorders

Neuromodulation is a treatment modality that can be used in the abortive and preventive treatment of migraine and other primary headache disorders. The basic concept of neurostimulation is to manipulate peripheral or central pain pathways with either magnetic or electrical impulses. Common neuromodulation techniques include occipital nerve stimulation, which is the oldest technique, and trigeminal nerve stimulation, combined occipital and trigeminal nerve stimulation, sphenopalatine ganglion stimulation, vagus nerve stimulation and transcranial magnetic stimulation, which were introduced soon after. The two newest modalities are remote electrical neuromodulation and caloric vestibular stimulation, the last of which is still in the experimental phases.

The influence of mandibular stretching on athletes subjected to high intensity workout.

The use of oral appliances is considered effective in improving sport performance. Jaw clenching or stretching, improved breathing or positioning of the jaw have been proposed to explain the improvement. In this study, we reported the effects of regularly practiced mandibular stretching at submaximal opening of the jaw in Crossfit athletes. Seventeen test subjects undergoing mandibular stretching (MS) showed significantly reduced (p0.001) performance time in a high-intensity workout measured before and after seven days of 10-minutes stretching practiced twice daily, while no improvement was observed in control subjects who did not perform the stretching. Additionally, blood lactate levels appeared to recover more quickly in MS subjects.Crossfit is a type of training regimen that pushes the limits of bodily recovery processes. Jaw stretching, eliciting the trigeminocardiac reflex (a reflex decrease in heart rate and blood pressure following trigeminal stimulation) and central oxygen-conserving mechanisms could help relieve post-training stress and improve training recovery.

External Trigeminal Nerve Stimulation as a Non-pharmacological Option for the Prevention and Acute Treatment of Migraine

Migraine is a common condition affecting approximately 1.04 billion people worldwide. Despite the available pharmaceutical therapies, patients with migraine often prefer, or may require, non-medicinal treatments for their disease. External trigeminal nerve stimulation (e-TNS) is a non-invasive, non-drug device treatment approved by the US Food and Drug Administration for the prevention and acute treatment of migraine. The trigeminovascular system plays a key role in migraine pathophysiology; e-TNS percutaneously stimulates the supraorbital and supratrochlear branches of the ophthalmic division of the trigeminal nerve. This article reviews published studies of e-TNS in the prevention and acute treatment of migraine, highlights the versatility of e-TNS in individualizing migraine treatment and discusses future directions for research and clinical applications of e-TNS therapy.