Purpose of Review
The number of applications for peripheral nerve stimulation (PNS) in the pain management field is ever-growing. With the increasing number of clinical applications for peripheral ...nerve stimulation, the purpose of this article is to review the mechanism of action surrounding PNS, the recent literature from January 2018 to January 2021, and pertinent clinical outcomes.
Recent Findings
The authors searched articles identified from PubMed (January 2018–January 2021), Cochrane Central Register of Controlled Trials databases (January 2018–January 2021), and Scopus (January 2018–January 2021) databases, and manually searched references of identified publications. Broad MeSH terms and Boolean operators were queried in each search, including the following terms and their respective synonyms: peripheral nerve stimulation, mechanism of action, biochemical pathway, and pain pathway. 15 consensus articles were selected for in-depth review and inclusion for qualitative analysis.
Summary
PNS may activate and modulate higher central nervous system (CNS) centers, including the dorsal lateral prefrontal cortex, somatosensory cortex, anterior cingulate cortex, and parahippocampal areas. Neuromodulatory effects from PNS may also extend into the spinal columns. Also, PNS may lead to changes in endogenous neurotransmitters and affect the plasticity of NMDA pathways.
Purpose of Review
Neuromodulation devices have become an attractive alternative to traditional pharmacotherapy for migraine, especially for patients intolerant to medication or who prefer ...non-pharmacological options. In the past decades, many studies demonstrated the efficacy of neuromodulation devices in patients with episodic migraine (EM). However, the benefit of these devices on chronic migraine (CM), which is typically more debilitating and refractory than EM, remains not well studied.
Recent Findings
We reviewed the literature within the last five years on using FDA-cleared and investigational devices for CM. There were eight randomized controlled trials and 15 open-label observational studies on ten neuromodulation devices.
Summary
Neuromodulation is promising for use in CM, although efficacy varies among devices or individuals. Noninvasive devices are usually considered safe with minimal adverse events. However, stimulation protocol and methodology differ between studies. More well-designed studies adhering to the guideline may facilitate FDA clearance and better insurance coverage.
Low-level vagus nerve stimulation through the tragus (tLLVNS) is increasingly acknowledged as a therapeutic strategy to prevent and treat atrial fibrillation. However, a lack in understanding of the ...exact antiarrhythmic properties of tLLVNS has hampered clinical implementation.
In this study, the authors aimed to study the effects of tLLVNS on atrial electrophysiology by performing intraoperative epicardial mapping during acute and chronic tLLVNS.
Epicardial mapping of the superior right atrium was performed before and after arterial graft harvesting in patients undergoing coronary artery bypass grafting without a history of atrial fibrillation. The time needed for arterial graft harvesting was used to perform chronic tLLVNS. Electrophysiological properties were compared before and during chronic tLLVNS.
A total of 10 patients (median age 74 years IQR: 69-78 years) underwent tLLVNS for a duration of 56 minutes (IQR: 43-73 minutes). During acute and chronic tLLVNS, a shift of the sinoatrial node exit site toward a more cranial direction was observed in 5 (50%) patients. Unipolar potential voltage increased significantly during acute and chronic tLLVNS (3.9 mV IQR: 3.1-4.8 mV vs 4.7 mV IQR: 4.0-5.3 mV vs 5.2 mV IQR: 4.8-7.0 mV; P = 0.027, P = 0.02, respectively). Total activation time, slope of unipolar potentials, amount of fractionation, low-voltage areas and conduction velocity did not differ significantly between baseline measurements and tLLVNS. Two patients showed consistent “improvement” of all electrophysiological properties during tLLVNS, while 1 patient appeared to have no beneficial effect.
We demonstrated that tLLVNS resulted in a significant increase in unipolar potential voltage. In addition, we observed the following in selective patients: 1) reduction in total activation time; 2) steeper slope of unipolar potentials; 3) decrease in the amount of fractionation; and 4) change in sinoatrial node exit sites.
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In the emerging research field of bioelectronic medicine, it has been indicated that neuromodulation of the vagus nerve (VN) has the potential to treat various conditions such as epilepsy, ...depression, and autoimmune diseases. In order to reduce side effects, as well as to increase the effectiveness of the delivered therapy, sub-fascicle stimulation specificity is required. In the electrical domain, increasing spatial selectivity can only be achieved using invasive and potentially damaging approaches like compressive forces or nerve penetration. To avoid these invasive methods while obtaining a high spatial selectivity, a 2-mm diameter extraneural cuff-shaped proof-of-concept design with integrated lead zirconate titanate (PZT) based ultrasound (US) transducers is proposed in this article. For the development of the proposed concept, wafer-level microfabrication techniques are employed. Moreover, acoustic measurements are performed on the device, in order to characterize the ultrasonic beam profiles of the integrated PZT-based US transducers. A focal spot size of around <inline-formula> <tex-math notation="LaTeX">200\times 200\,\,\mu \text{m} </tex-math></inline-formula> is measured for the proposed cuff. Moreover, the curvature of the device leads to constructive interference of the US waves originating from multiple PZT-based US transducers, which in turn leads to an increase of 45% in focal pressure compared to the focal pressure of a single PZT-based US transducer. Integrating PZT-based US transducers in an extraneural cuff-shaped design has the potential to achieve high-precision US neuromodulation of the VN without requiring intraneural implantation.
Chronic pelvic pain conditions such as pudendal neuralgia pose significant treatment difficulty due to their elusive etiology and diverse symptomatology. Initially approved as a third or fourth-line ...treatment of non-obstructive urinary retention and fecal incontinence, neuromodulation has also proven effective for pelvic pain associated with urinary dysfunction. Recently, sacral and pudendal neuromodulation has demonstrated efficacy in managing a spectrum of chronic pelvic conditions including refractory pudendal neuralgia. The individualized approach of peripheral neuromodulation has opened new avenues for tailored medical interventions, extending its application to conditions such as pudendal neuralgia, post sling pain, and vulvodynia. New technologies leading to miniaturized neuromodulation devices such as Freedom
®
stimulators (Curonix), allows us to implant leads and modulate nerves at precise pain targets. Further experience and research is needed to assess the impact of targeted neuromodulation on managing complex pelvic pain conditions.
Introduction: One of the Physiotherapist objectives is the identification of neuromotor circuits that can be reactivated after the Stroke. The selection of motor and sensory modeling pathways that ...contribute to the recovery of impaired movements
1
depends on the acquired neuromotor learning throughout life
2
. In this approach, the stimulation of automatic gestures is paramount. In addition, rhythmic auditory stimuli, such as music, have been associated with optimized motor responses following brain injury
3
,
4
. Subsequently, exposing individuals to familiar and proper music can re-activate movements, which generate patterns previously learned, such as dance.
Materials and methods: A 47-year-old man, native of Cape Verde, with the diagnosis of stroke, underwent a decompressive craniotomy, with 4-month. He presented hemiparesis of the right hemisphere and aphasia. During the physiotherapy sessions he underwent sensorineural stimulation to reactivate automatic motor circuits. This was accomplished through exposure to familiar music sound, in order to reactivate the standard automatic dance motor, learned before brain injury. The motion analysis was performed by direct observation and recorded through video, orthostatic position and gait phases, at the following moments: before, during and after neurosensory stimulation (music). This study follows all the principles of the Declaration of Helsinki.
Results: There was an increase in gait velocity (during and after neurosensory stimulation), as well as an increase in the activation of the dorsal flexors (paretic lower limb) during the oscillating phase. In the qualitative observation, the optimization of the orthostatic position was verified, namely in the weight transfer capacity, for the paretic lower limb.
Discussion and conclusions: The interaction of the automatic motor gestures reactivation with the neurosensorial stimulation, in the scope of Physiotherapy promotes a reflection on the current clinical practice. It is important to consider the possible relevance of investing and developing approaches that focus more on the specialization of stimuli applied to the recovery of the individual with stroke.
The results found in this clinical case can be based on the fact that the hearing of rhythmic sounds induced by music trigger the motor centers of the basal ganglia, also theoretically associated with the neural circuits of the automatic movements. To better understand these mechanisms, and fundament as an intervention tool, it will be necessary to develop research on sensorineural stimulation in the reactivation of automatic motor circuits after stroke.
Non‐invasive brain stimulation has the potential to boost neuronal plasticity in the primary motor cortex (M1), but it remains unclear whether the stimulation of both superficial and deep layers of ...the human motor cortex can effectively promote M1 plasticity. Here, we leveraged transcranial ultrasound stimulation (TUS) to precisely target M1 circuits at depths of approximately 5 mm and 16 mm from the cortical surface. Initially, we generated computed tomography images from each participant's individual anatomical magnetic resonance images (MRI), which allowed for the generation of accurate acoustic simulations. This process ensured that personalized TUS was administered exactly to the targeted depths within M1 for each participant. Using long‐term depression and long‐term potentiation (LTD/LTP) theta‐burst stimulation paradigms, we examined whether TUS over distinct depths of M1 could induce LTD/LTP plasticity. Our findings indicated that continuous theta‐burst TUS‐induced LTD‐like plasticity with both superficial and deep M1 stimulation, persisting for at least 30 min. In comparison, sham TUS did not significantly alter M1 excitability. Moreover, intermittent theta‐burst TUS did not result in the induction of LTP‐ or LTD‐like plasticity with either superficial or deep M1 stimulation. These findings suggest that the induction of M1 plasticity can be achieved with ultrasound stimulation targeting distinct depths of M1, which is contingent on the characteristics of TUS.
Key points
The study integrated personalized transcranial ultrasound stimulation (TUS) with electrophysiology to determine whether TUS targeting superficial and deep layers of the human motor cortex (M1) could elicit long‐term depression (LTD) or long‐term potentiation (LTP) plastic changes.
Utilizing acoustic simulations derived from individualized pseudo‐computed tomography scans, we ensured the precision of TUS delivery to the intended M1 depths for each participant.
Continuous theta‐burst TUS targeting both the superficial and deep layers of M1 resulted in the emergence of LTD‐like plasticity, lasting for at least 30 min.
Administering intermittent theta‐burst TUS to both the superficial and deep layers of M1 did not lead to the induction of LTP‐ or LTD‐like plastic changes.
We suggest that theta‐burst TUS targeting distinct depths of M1 can induce plasticity, but this effect is dependent on specific TUS parameters.
figure legend Transcranial ultrasound stimulation (TUS) was applied to specifically target motor cortex (M1) circuits at depths of about 5 mm and 16 mm from the cortical surface. Employing theta‐burst stimulation paradigms associated with long‐term depression and potentiation (LTD/LTP), this study investigated the potential of TUS at varying M1 depths to elicit LTD/LTP plasticity. The results showed that continuous theta‐burst TUS led to LTD‐like plasticity in both superficial and deep M1 areas, with effects lasting at least 30 min. In contrast, intermittent theta‐burst TUS failed to induce LTP‐ or LTD‐like plasticity in either superficial or deep M1 stimulation.
Parkinson’s disease (PD) patients often suffer from spinal diseases requiring surgeries, although the risk of complications is high. There are few reports on outcomes after spinal surgery for PD ...patients with deep brain stimulation (DBS). The objective of this study was to explore the data on spinal surgery for PD patients with precedent DBS. We evaluated 24 consecutive PD patients with 28 spinal surgeries from 2007 to 2017 who received at least a 2-year follow-up. The characteristics and outcomes of PD patients after spinal surgery were compared to those of 156 non-PD patients with degenerative spinal diseases treated in 2013–2017. Then, the characteristics, outcomes, and spinal alignment of PD patients receiving DBS were analyzed in degenerative spinal/lumbar diseases. The mean age at the time of spinal surgery was 68 years. The Hoehn and Yahr score regarding PD was stage 1 for 8 patients, stage 2 for 2 patients, stage 3 for 8 patients, stage 4 for 10 patients, and stage 5 for 0 patient. The median preoperative L-DOPA equivalent daily dose was 410 mg. Thirteen patients (46%) received precedent subthalamic nucleus (STN) DBS. Lumbar lesions with pain were common, and operation and anesthesia times were long in PD patients. Pain and functional improvement of PD patients persisted for 2 years after surgery with a higher complication rate than for non-PD patients. PD patients with STN DBS maintained better lumbar lordosis for 2 years after spinal surgery. STN DBS significantly maintained spinal alignment with subsequent pain and functional amelioration 2 years after surgery. The outcomes of spinal surgery for PD patients might be favorably affected by thorough treatment for PD including DBS.
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