Neuromodulation for chronic pain.

Neuromodulation is an expanding area of pain medicine that incorporates an array of non-invasive, minimally invasive, and surgical electrical therapies. In this Series paper, we focus on spinal cord stimulation (SCS) therapies discussed within the framework of other invasive, minimally invasive, and non-invasive neuromodulation therapies. These therapies include deep brain and motor cortex stimulation, peripheral nerve stimulation, and the non-invasive treatments of repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and transcutaneous electrical nerve stimulation. SCS methods with electrical variables that differ from traditional SCS have been approved. Although methods devoid of paraesthesias (eg, high frequency) should theoretically allow for placebo-controlled trials, few have been done. There is low-to-moderate quality evidence that SCS is superior to reoperation or conventional medical management for failed back surgery syndrome, and conflicting evidence as to the superiority of traditional SCS over sham stimulation or between different SCS modalities. Peripheral nerve stimulation technologies have also undergone rapid development and become less invasive, including many that are placed percutaneously. There is low-to-moderate quality evidence that peripheral nerve stimulation is effective for neuropathic pain in an extremity, low quality evidence that it is effective for back pain with or without leg pain, and conflicting evidence that it can prevent migraines. In the USA and many areas in Europe, deep brain and motor cortex stimulation are not approved for chronic pain, but are used off-label for refractory cases. Overall, there is mixed evidence supporting brain stimulation, with most sham-controlled trials yielding negative findings. Regarding non-invasive modalities, there is moderate quality evidence that repetitive transcranial magnetic stimulation does not provide meaningful benefit for chronic pain in general, but conflicting evidence regarding pain relief for neuropathic pain and headaches. For transcranial direct current stimulation, there is low-quality evidence supporting its benefit for chronic pain, but conflicting evidence regarding a small treatment effect for neuropathic pain and headaches. For transcutaneous electrical nerve stimulation, there is low-quality evidence that it is superior to sham or no treatment for neuropathic pain, but conflicting evidence for non-neuropathic pain. Future research should focus on better evaluating the short-term and long-term effectiveness of all neuromodulation modalities and whether they decrease health-care use, and on refining selection criteria and treatment variables.

Transcranial direct current stimulation in combination with cognitive training in individuals with mild cognitive impairment: a controlled 3-parallel-arm study.

OBJECTIVE: Several studies showed that transcranial direct current stimulation (tDCS) enhances cognition in patients with mild cognitive impairment (MCI), however, whether tDCS leads to additional gains when combined with cognitive training remains unclear. This study aims to compare the effects of a concurrent tDCS-cognitive training intervention with either tDCS or cognitive training alone on a group of patients with MCI. METHODS: The study was a 3-parallel-arm study. The intervention consisted of 20 daily sessions of 20 minutes each. Patients (n = 62) received anodal tDCS to the left dorsolateral prefrontal cortex, cognitive training on 5 cognitive domains (orientation, attention, memory, language, and executive functions), or both. To examine intervention gains, we examined global cognitive functioning, verbal short-term memory, visuospatial memory, and verbal fluency pre- and post-intervention. RESULTS: All outcome measures improved after the intervention in the 3 groups. The improvement in global cognitive functioning and verbal fluency was significantly larger in patients who received the combined intervention. Instead, the intervention gain in verbal short-term memory and visuospatial memory was similar across the 3 groups. DISCUSSION: tDCS, regardless of the practicalities, could be an efficacious treatment in combination with cognitive training given the increased effectiveness of the combined treatment. CONCLUSIONS: Future studies will need to consider individual differences at baseline, including genetic factors and anatomical differences that impact the electric field generated by tDCS and should also consider the feasibility of at-home treatments consisting of the application of tDCS with cognitive training.

Automatic M1-SO Montage Headgear for Transcranial Direct Current Stimulation (TDCS) Suitable for Home and High-Throughput In-Clinic Applications.

OBJECTIVES: Non-invasive transcranial direct current stimulation (tDCS) over the motor cortex is broadly investigated to modulate functional outcomes such as motor function, sleep characteristics, or pain. The most common montages that use two large electrodes (25-35 cm2 ) placed over the area of motor cortex and contralateral supraorbital region (M1-SO montages) require precise measurements, usually using the 10-20 EEG system, which is cumbersome in clinics and not suitable for applications by patients at home. The objective was to develop and test novel headgear allowing for reproduction of the M1-SO montage without the 10-20 EEG measurements, neuronavigation, or TMS. MATERIALS AND METHODS: Points C3/C4 of the 10-20 EEG system is the conventional reference for the M1 electrode. The headgear was designed using an orthogonal, fixed-angle approach for connection of frontal and coronal headgear components. The headgear prototype was evaluated for accuracy and replicability of the M1 electrode position in 600 repeated measurements compared to manually determined C3 in 30 volunteers. Computational modeling was used to estimate brain current flow at the mean and maximum recorded electrode placement deviations from C3. RESULTS: The headgear includes navigational points for accurate placement and assemblies to hold electrodes in the M1-SO position without measurement by the user. Repeated measurements indicated accuracy and replicability of the electrode position: the mean [SD] deviation of the M1 electrode (size 5 × 5 cm) from C3 was 1.57 [1.51] mm, median 1 mm. Computational modeling suggests that the potential deviation from C3 does not produce a significant change in brain current flow. CONCLUSIONS: The novel approach to M1-SO montage using a fixed-angle headgear not requiring measurements by patients or caregivers facilitates tDCS studies in home settings and can replace cumbersome C3 measurements for clinical tDCS applications.

Pain-related distress among patients referred to a community-based palliative care program.

OBJECTIVE: Numerous studies have characterized the pain reported by patients with advanced illness in terms of descriptors such as severity, but few have measured pain-related distress. Distress may be important in the clinical approach to pain. To evaluate pain-related distress among adult patients with advanced illness and pain following enrollment in an urban, specialist-level, community-based palliative care program. METHOD: In a retrospective cross-sectional analysis, data were extracted from the electronic health records of all patients who were able to complete the pain item from the Condensed Memorial Symptom Assessment Scale at the start of care. Bivariate and multivariate analyses evaluated the associations between distress and both sociodemographics and disease-related information. RESULTS: The 506 patients completing the pain item had a mean (SD) age of 70.7 years (13.8); 64.2% were women, 32.1% were Hispanic, 32.6% were white, and 27.7% were black. Of the 503 patients who indicated some level of distress on a 0-4 scale, 221 (43.7%) had high distress, defined as a score ≥3 ("quite a bit" or "very much"). Cancer diagnosis and poor performance status (unable to care for self) were predictors of high pain-related distress (both p < 0.05).Significance of resultsAmong patients with advanced illness who reported pain at the start of care by a specialist palliative care program, high pain-related distress was common, particularly among those with cancer or poor physical function. Further studies are needed to explore the extent to which pain-related distress should inform the assessment and management of pain.

A qualitative study to explore psychological distress and illness burden associated with opioid-induced constipation in cancer patients with advanced disease.

BACKGROUND: Constipation affects many patients receiving long-term opioid therapy for cancer pain. Little is known about the nature of psychological distress and the burden associated with this problem. This information may inform the development of effective treatment strategies and ameliorate distress. AIM: The objective was to use qualitative research methods to better understand psychological distress and the burden associated with opioid-induced constipation and its treatment in advanced cancer patients. DESIGN: In this qualitative study, semi-structured interviews explored perceptions of psychological distress and burden from opioid-induced constipation. Interviews were analyzed using a thematic content analysis approach involving descriptive and interpretive coding and identification of recurring themes. SETTING/PARTICIPANTS: Twelve advanced cancer patients with opioid-induced constipation were recruited from a large urban hospital. RESULTS: Patients experienced various types of negative affect and cognitions associated with opioid-induced constipation. Analyses indicated three major themes: (1) irrational thoughts and educational needs; (2) psychological distress from constipation and (3) the effects of constipation on the decision to use opioid analgesics. Irrational thoughts and educational needs included beliefs that nutrition could improve constipation, the supposition that constipation indicated deteriorating health, and catastrophic beliefs. Psychological distress included depressive symptoms and anticipatory anxiety related to constipation. Decision-making revealed cognitive dissonance about using opioids and conflicting preferences about continuing use. CONCLUSIONS: Future investigation of the multiple components of cognitive and affective burden from opioid-induced constipation is warranted. Understanding the varied nature of this burden may improve clinical recognition and assessment and promote more intensive management consistent with the distress it produces.

Delivery of an at-home transcranial direct current stimulation intervention to mitigate pain in patients with end-stage kidney disease receiving hemodialysis (ESKD/HD).

Background: Poorly controlled pain remains a problem for many patients with end-stage kidney disease requiring hemodialysis (ESKD/HD) and customary approaches to pain management (e.g., opioids, non-steroidals) confer substantial risk. Accordingly, non-pharmacologic therapies are needed for use in this population. Non-invasive transcranial Direct Current Simulation (tDCS) constitutes a promising nonpharmacologic method for pain management in affected individuals. Aims: This study seeks to: 1) determine the effects of an 8-week course of at-home tDCS vs. sham tDCS on pain intensity, pain interference, medication usage, quality of life, and mood; 2) determine if tDCS effects vary by race/ethnicity; and 3) ascertain patient satisfaction with device use. Methods: This double-blind, randomized, sham-controlled clinical trial will enroll 100 ESKD/HD patients with moderate-to-severe (≥4 on 0-10 scale) chronic pain. The active study intervention consists of 20 min of tDCS delivered over the primary motor cortex 5 days/week for 8 weeks. The comparator is a sham procedure that provides no effective stimulation. The primary outcome analysis will evaluate efficacy of tDCS for pain reduction after two months of stimulation. We will also assess the effects of treatment on analgesic consumption, pain interference, depressed mood, and quality of life. The statistical plan will include fixed classification factors for treatment (vs. sham), clinic sites, and assessment time, and the interaction of these factors adjusting for covariates (e.g., race/ethnicity, pain level). Conclusion: At-home tDCS constitutes a promising nonpharmacologic treatment for pain mitigation in persons with ESKD/HD. This unique RCT could transform the way pain is managed in this vulnerable population. Trial Registration: NCT05311956.

Developing patient-centered treatment protocols in brain stimulation: a rationale for combining quantitative and qualitative approaches in persons with HIV.

This article reports and discusses how quantitative (physiological and behavioral) and qualitative methods are being combined in an open-label pilot feasibility study. The study evaluates safety, tolerability, and acceptability of a protocol to treat depression in HIV-infected individuals, using a 2-week block of transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex. Major depressive disorder (MDD) is the second most prevalent psychiatric disorder after substance abuse among HIV-positive adults, and novel antidepressant treatments are needed for this vulnerable population. The authors describe the challenges and contributions derived from different research perspectives and methodological approaches and provide a philosophical framework for combining quantitative and qualitative measurements for a fuller examination of the disorder. Four methodological points are presented: (1) the value of combining quantitative and qualitative approaches; (2) the need for context-specific measures when studying patients with medical and psychiatric comorbidities; (3) the importance of research designs that integrate physiological, behavioral, and qualitative approaches when evaluating novel treatments; and (4) the need to explore the relationships between biomarkers, clinical symptom assessments, patient self-evaluations, and patient experiences when developing new, patient-centered protocols. The authors conclude that the complexity of studying novel treatments in complex and new patient populations requires complex research designs to capture the richness of data that inform translational research.

Feasibility and Acceptability of a Pharmacogenomic Decision Support System in Palliative Care.

Context: Pharmacogenomic analysis may improve the efficacy or safety of the drugs used in palliative care. Decision support systems may promote clinical integration of this information. Objectives: To determine the feasibility and acceptability of a pharmacist-directed pharmacogenomic decision support system in the care of patients with advanced illness and explore the drug-gene and drug-drug interactions that occur in this population. Methods: Physicians or nurse practitioners from two U.S. hospice agencies identified opioid-treated patients receiving multiple other drugs. Buccal samples and clinical data were obtained from consenting patients. A pharmacist used the proprietary MedWise™ platform to evaluate the current medications in terms of genotype and phenotype, created a standardized report describing potential interactions and recommended actions that may reduce the associated risk. Clinicians could access the report online and completed Likert-type scales to assess use and satisfaction with the system. Results: Twenty clinicians and 100 patients participated. The reports revealed that 74 drugs were subject to 462 drug-gene interactions and 77 were involved in 691 drug-drug interactions; only 4 and 16 patients, respectively, had no drug-gene or drug-drug interactions. Clinicians routinely checked the reports and used the information to change ≥1 treatments in 55 (55%) patients. Almost all clinicians rated the system likely to improve the quality of care and all "agreed" or "strongly agreed" to recommend the system to colleagues. Conclusion: This pharmacist-directed pharmacogenomic decision support system was perceived positively and was integrated into practice. Further studies are warranted to its clinical integration and its outcomes.

Neurostimulation for cognitive enhancement in Alzheimer's disease (the NICE-AD study): a randomized clinical trial.

New therapies for symptoms in Alzheimer's disease (AD) are urgently needed. Prior studies suggest that transcranial direct current stimulation (tDCS), a noninvasive neuromodulatory method, may be a safe and potentially effective treatment, but conclusions have been limited by small-sample sizes and brief stimulation protocols. This double-blind randomized trial involving 100 older adults with mild-to-moderate AD examines effects of 6 months of at-home active tDCS or sham delivered over the dorsolateral prefrontal cortex. The primary outcome is global cognitive performance. Secondary outcomes include executive-control/spatial selective attention, functional neuroplasticity, depressive symptoms, quality of life and the durability of effects 3 months after the stimulation period. The results will provide evidence on the efficacy of multimonth at-home tDCS in the AD treatment. =Clinical trial identifier NCT04404153 (Clinicaltrials.gov).

Providing End-of-Life Care for Patients With Left Ventricular Assist Devices: Experience of a Hospice Agency.

CONTEXT: Patients with left ventricular assist devices (LVADs) need expert palliative care at the end of life. In the U.S., hospice may provide this care, but few patients enroll, and information about hospice experience with LVAD-implanted patients is limited. OBJECTIVE: To describe hospice experience with LVAD-implanted patients. METHODS: This is a retrospective descriptive study of all LVAD-implanted patients admitted to a hospice agency. Data were extracted from the electronic health record. RESULTS: The 13 patients had a mean age of 63 years (range 20-89) and a mean LVAD duration of 32.5 months (range 8.2-70.0). Hospice diagnosis was heart failure in 10 patients and cancer in three patients; all patients were multimorbid. Eight patients enrolled in hospice on one occasion, four had two enrollments, and one had five. All patients received services for <180 days, three for <7 days, and four patients for >90 days. Just-in-time inservicing was used to prepare hospice teams for challenging care needs, including bleeding, delirium, infections, and mechanical failure. Of the nine patients who died while receiving hospice services, one enrolled with a plan to deactivate the LVAD immediately after hospice enrollment, and six died after discontinuation of the LVAD or other life-sustaining therapy during the course of hospice care. Five deaths occurred in a hospice inpatient unit. CONCLUSION: To provide specialist palliative care to LVAD-implanted patients, hospices must be prepared to manage complex and highly varied needs. To do this, hospices must have adequate staff support and access to acute care.

Updated Technique for Reliable, Easy, and Tolerated Transcranial Electrical Stimulation Including Transcranial Direct Current Stimulation.

Transcranial direct current stimulation (tDCS) is a noninvasive method of neuromodulation using low-intensity direct electrical currents. This method of brain stimulation presents several potential advantages compared to other techniques, as it is noninvasive, cost-effective, broadly deployable, and well-tolerated provided proper equipment and protocols are administered. Even though tDCS is apparently simple to perform, correct administration of the tDCS session, especially the electrode positioning and preparation, is vital for ensuring reproducibility and tolerability. The electrode positioning and preparation steps are traditionally also the most time consuming and error-prone. To address these challenges, modern tDCS techniques, using fixed-position headgear and pre-assembled sponge electrodes, reduce complexity and setup time while also ensuring that the electrodes are consistently placed as intended. These modern tDCS methods present advantages for research, clinic, and remote-supervised (at home) settings. This article provides a comprehensive step-by-step guide for administering a tDCS session using fixed-position headgear and pre-assembled sponge electrodes. This guide demonstrates tDCS using commonly applied montages intended for motor cortex and dorsolateral prefrontal cortex (DLPFC) stimulation. As described, selection of the head size and montage-specific headgear automates electrode positioning. Fully assembled pre-saturated snap-electrodes are simply affixed to the set position snap-connectors on the headgear. The modern tDCS method is shown to reduce setup time and reduce errors for both novice and expert operators. The methods outlined in this article can be adapted to different applications of tDCS as well as other forms of transcranial electrical stimulation (tES) such as transcranial alternating current stimulation (tACS) and transcranial random noise stimulation (tRNS). However, since tES is application specific, as appropriate, any methods recipe is customized to accommodate subject, indication, environment, and outcome specific features.

Supervised transcranial direct current stimulation (tDCS) at home: A guide for clinical research and practice.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a method of noninvasive neuromodulation and potential therapeutic tool to improve functioning and relieve symptoms across a range of central and peripheral nervous system conditions. Evidence suggests that the effects of tDCS are cumulative with consecutive daily applications needed to achieve clinically meaningful effects. Therefore, there is growing interest in delivering tDCS away from the clinic or research facility, usually at home. OBJECTIVE: To provide a comprehensive guide to operationalize safe and responsible use of tDCS in home settings for both investigative and clinical use. METHODS: Providing treatment at home can improve access and compliance by decreasing the burden of time and travel for patients and their caregivers, as well as to reach those in remote locations and/or living with more advanced disabilities. RESULTS: To date, methodological approaches for at-home tDCS delivery have varied. After implementing the first basic guidelines for at-home tDCS in clinical trials, this work describes a comprehensive guide for facilitating safe and responsible use of tDCS in home settings enabling access for repeated administration over time. CONCLUSION: These guidelines provide a reference and standard for practice when employing the use of tDCS outside of the clinic setting.

Effects of transcranial direct current stimulation on addictive behavior and brain glucose metabolism in problematic online gamers.

BACKGROUND AND AIMS: Some online gamers may encounter difficulties in controlling their gaming behavior. Previous studies have demonstrated beneficial effects of transcranial direct current stimulation (tDCS) on various kinds of addiction. This study investigated the effects of tDCS on addictive behavior and regional cerebral metabolic rate of glucose (rCMRglu) in problematic online gamers. METHODS: Problematic online gamers were randomized and received 12 sessions of either active (n = 13) or sham tDCS (n = 13) to the dorsolateral prefrontal cortex over 4 weeks (anode F3/cathode F4, 2 mA for 30 min, 3 sessions per week). Participants underwent brain 18F-fluoro-2-deoxyglucose positron emission tomography scans and completed questionnaires including the Internet Addiction Test (IAT), Brief Self-Control Scale (BSCS), and Behavioral Inhibition System/Behavioral Activation System scales (BIS/BAS) at the baseline and 4-week follow-up. RESULTS: Significant decreases in time spent on gaming (P = 0.005), BIS (P = 0.03), BAS-fun seeking (P = 0.04), and BAS-reward responsiveness (P = 0.01), and increases in BSCS (P = 0.03) were found in the active tDCS group, while decreases in IAT were shown in both groups (P < 0.001). Group-by-time interaction effects were not significant for these measures. Increases in BSCS scores were correlated with decreases in IAT scores in the active group (ß = -0.85, P < 0.001). rCMRglu in the left putamen, pallidum, and insula was increased in the active group compared to the sham group (P for interaction < 0.001). DISCUSSION AND CONCLUSIONS: tDCS may be beneficial for problematic online gaming potentially through changes in self-control, motivation, and striatal/insular metabolism. Further larger studies with longer follow-up period are warranted to confirm our findings.

Guidelines for TMS/tES clinical services and research through the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has broadly disrupted biomedical treatment and research including non-invasive brain stimulation (NIBS). Moreover, the rapid onset of societal disruption and evolving regulatory restrictions may not have allowed for systematic planning of how clinical and research work may continue throughout the pandemic or be restarted as restrictions are abated. The urgency to provide and develop NIBS as an intervention for diverse neurological and mental health indications, and as a catalyst of fundamental brain research, is not dampened by the parallel efforts to address the most life-threatening aspects of COVID-19; rather in many cases the need for NIBS is heightened including the potential to mitigate mental health consequences related to COVID-19. OBJECTIVE: To facilitate the re-establishment of access to NIBS clinical services and research operations during the current COVID-19 pandemic and possible future outbreaks, we develop and discuss a framework for balancing the importance of NIBS operations with safety considerations, while addressing the needs of all stakeholders. We focus on Transcranial Magnetic Stimulation (TMS) and low intensity transcranial Electrical Stimulation (tES) - including transcranial Direct Current Stimulation (tDCS) and transcranial Alternating Current Stimulation (tACS). METHODS: The present consensus paper provides guidelines and good practices for managing and reopening NIBS clinics and laboratories through the immediate and ongoing stages of COVID-19. The document reflects the analysis of experts with domain-relevant expertise spanning NIBS technology, clinical services, and basic and clinical research - with an international perspective. We outline regulatory aspects, human resources, NIBS optimization, as well as accommodations for specific demographics. RESULTS: A model based on three phases (early COVID-19 impact, current practices, and future preparation) with an 11-step checklist (spanning removing or streamlining in-person protocols, incorporating telemedicine, and addressing COVID-19-associated adverse events) is proposed. Recommendations on implementing social distancing and sterilization of NIBS related equipment, specific considerations of COVID-19 positive populations including mental health comorbidities, as well as considerations regarding regulatory and human resource in the era of COVID-19 are outlined. We discuss COVID-19 considerations specifically for clinical (sub-)populations including pediatric, stroke, addiction, and the elderly. Numerous case-examples across the world are described. CONCLUSION: There is an evident, and in cases urgent, need to maintain NIBS operations through the COVID-19 pandemic, including anticipating future pandemic waves and addressing effects of COVID-19 on brain and mind. The proposed robust and structured strategy aims to address the current and anticipated future challenges while maintaining scientific rigor and managing risk.

Effects of 6-month at-home transcranial direct current stimulation on cognition and cerebral glucose metabolism in Alzheimer's disease.

BACKGROUND: Although single or multiple sessions of transcranial direct current stimulation (tDCS) on the prefrontal cortex over a few weeks improved cognition in patients with Alzheimer's disease (AD), effects of repeated tDCS over longer period and underlying neural correlates remain to be elucidated. OBJECTIVE: This study investigated changes in cognitive performances and regional cerebral metabolic rate for glucose (rCMRglc) after administration of prefrontal tDCS over 6 months in early AD patients. METHODS: Patients with early AD were randomized to receive either active (n = 11) or sham tDCS (n = 7) over the dorsolateral prefrontal cortex (DLPFC) at home every day for 6 months (anode F3/cathode F4, 2 mA for 30 min). All patients underwent neuropsychological tests and brain 18F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) scans at baseline and 6-month follow-up. Changes in cognitive performances and rCMRglc were compared between the two groups. RESULTS: Compared to sham tDCS, active tDCS improved global cognition measured with Mini-Mental State Examination (p for interaction = 0.02) and language function assessed by Boston Naming Test (p for interaction = 0.04), but not delayed recall performance. In addition, active tDCS prevented decreases in executive function at a marginal level (p for interaction < 0.10). rCMRglc in the left middle/inferior temporal gyrus was preserved in the active group, but decreased in the sham group (p for interaction < 0.001). CONCLUSIONS: Daily tDCS over the DLPFC for 6 months may improve or stabilize cognition and rCMRglc in AD patients, suggesting the therapeutic potential of repeated at-home tDCS.

Transcranial electrical stimulation nomenclature.

Transcranial electrical stimulation (tES) aims to alter brain function non-invasively by applying current to electrodes on the scalp. Decades of research and technological advancement are associated with a growing diversity of tES methods and the associated nomenclature for describing these methods. Whether intended to produce a specific response so the brain can be studied or lead to a more enduring change in behavior (e.g. for treatment), the motivations for using tES have themselves influenced the evolution of nomenclature, leading to some scientific, clinical, and public confusion. This ambiguity arises from (i) the infinite parameter space available in designing tES methods of application and (ii) varied naming conventions based upon the intended effects and/or methods of application. Here, we compile a cohesive nomenclature for contemporary tES technologies that respects existing and historical norms, while incorporating insight and classifications based on state-of-the-art findings. We consolidate and clarify existing terminology conventions, but do not aim to create new nomenclature. The presented nomenclature aims to balance adopting broad definitions that encourage flexibility and innovation in research approaches, against classification specificity that minimizes ambiguity about protocols but can hinder progress. Constructive research around tES classification, such as transcranial direct current stimulation (tDCS), should allow some variations in protocol but also distinguish from approaches that bear so little resemblance that their safety and efficacy should not be compared directly. The proposed framework includes terms in contemporary use across peer-reviewed publications, including relatively new nomenclature introduced in the past decade, such as transcranial alternating current stimulation (tACS) and transcranial pulsed current stimulation (tPCS), as well as terms with long historical use such as electroconvulsive therapy (ECT). We also define commonly used terms-of-the-trade including electrode, lead, anode, and cathode, whose prior use, in varied contexts, can also be a source of confusion. This comprehensive clarification of nomenclature and associated preliminary proposals for standardized terminology can support the development of consensus on efficacy, safety, and regulatory standards.

Capsaicin (TRPV1 Agonist) therapy for pain relief: farewell or revival?

OBJECTIVE: In this review, we explain our current understanding of the molecular basis for pain relief by capsaicin and other transient receptor potential vanilloid subfamily, member 1 (TRPV1) agonists. We summarize disease-related changes in TRPV1 expression and its implications for therapy and potential adverse effects. Last, we provide an overview of the current clinical uses of topical and injectable TRPV1 agonist preparations in both oncologic and nononcologic populations. METHOD: Search of MEDLINE and other databases. RESULTS: The capsaicin receptor TRPV1 is a polymodal nociceptor exhibiting a dynamic threshold of activation that could be lowered under inflammatory conditions. Consistent with this model, TRPV1 knock-out mice are devoid of post-inflammatory thermal hyperalgesia. TRPV1 desensitization of primary sensory neurons is a powerful approach to relieve symptoms of nociceptive behavior in animal models of chronic pain. However, over-the-counter capsaicin creams have shown moderate to poor analgesic efficacy. This is in part related to low dose, poor skin absorption, and compliance factors. Recently developed site-specific capsaicin therapy with high-dose patches and injectable preparations seem to be safe and reportedly provide long-lasting analgesia with rapid onset. CONCLUSIONS: We argue that TRPV1 agonists and antagonists are not mutually exclusive but rather complimentary pharmacologic approaches for pain relief and we predict a "revival" for capsaicin and other TRPV1 agonists in the clinical management of pain associated with inflammation, metabolic imbalances (eg, diabetes), infections (HIV), and cancer, despite the current focus of the pharmaceutical industry on TRPV1 antagonists.

At-Home Transcranial Direct Current Stimulation (tDCS) With Telehealth Support for Symptom Control in Chronically-Ill Patients With Multiple Symptoms.

Transcranial direct current stimulation (tDCS) delivered in multiple sessions can reduce symptom burden, but access of chronically ill patients to tDCS studies is constrained by the burden of office-based tDCS administration. Expanded access to this therapy can be accomplished through the development of interventions that allow at-home tDCS applications. Objective: We describe the development and initial feasibility assessment of a novel intervention for the chronically ill that combines at-home tDCS with telehealth support. Methods: In the developmental phase, the tDCS procedure was adjusted for easy application by patients or their informal caregivers at home, and a tDCS protocol with specific elements for enhanced safety and remote adherence monitoring was created. Lay language instructional materials were written and revised based on expert feedback. The materials were loaded onto a tablet allowing for secure video-conferencing. The telehealth tablet was paired with an at-home tDCS device that allowed for remote dose control via electronic codes dispensed to patients prior to each session. tDCS was delivered in two phases: once daily on 10 consecutive days, followed by an as needed regimen for 20 days. Initial feasibility of this tDCS-telehealth system was evaluated in four patients with advanced chronic illness and multiple symptoms. Change in symptom burden and patient satisfaction were assessed with the Condensed Memorial Symptom Assessment Scale (CMSAS) and a tDCS user survey. Results: The telehealth-tDCS protocol includes one home visit and has seven patient-tailored elements and six elements enhancing safety monitoring. Replicable electrode placement at home without 10-20 EEG measurement is achieved via a headband that holds electrodes in a pre-determined position. There were no difficulties with patients' training, protocol adherence, or tolerability. A total of 60 tDCS sessions were applied. No session required discontinuation, and there were no adverse events. Data collection was feasible and there were no missing data. Satisfaction with the tDCS-telehealth procedure was high and the patients were comfortable using the system. Conclusion: At-home tDCS with telehealth support appears to be a feasible approach for the management of symptom burden in patients with chronic illness. Further studies to evaluate and optimize the protocol effectiveness for symptom-control outcomes are warranted.