Neuromodulation: Journals & articles

Abstract
Background and objective: Repetitive transcranial magnetic stimulation (rTMS) applied to the motor cortex provides supplementary relief for some individuals with chronic pain who are refractory to pharmacological treatment. As rTMS slowly enters treatment guidelines for pain relief, its starts to be confronted with challenges long known to pharmacological approaches: efficacy at the group-level does not grant pain relief for a particular patient. In this review, we present and discuss a series of ongoing attempts to overcome this therapeutic challenge in a personalized medicine framework.

Databases and data treatment: Relevant scientific publications published in main databases such as PubMed and EMBASE from inception until March 2023 were systematically assessed, as well as a wide number of studies dedicated to the exploration of the mechanistic grounds of rTMS analgesic effects in humans, primates and rodents.

Results: The main strategies reported to personalize cortical neuromodulation are: (i) the use of rTMS to predict individual response to implanted motor cortex stimulation; (ii) modifications of motor cortex stimulation patterns; (iii) stimulation of extra-motor targets; (iv) assessment of individual cortical networks and rhythms to personalize treatment; (v) deep sensory phenotyping; (vi) personalization of location, precision and intensity of motor rTMS. All approaches except (i) have so far low or moderate levels of evidence.

Conclusions: Although current evidence for most strategies under study remains at best moderate, the multiple mechanisms set up by cortical stimulation are an advantage over single-target 'clean' drugs, as they can influence multiple pathophysiologic paths and offer multiple possibilities of individualization.

Significance: Non-invasive neuromodulation is on the verge of personalised medicine. Strategies ranging from integration of detailed clinical phenotyping into treatment design to advanced patient neurophysiological characterisation are being actively explored and creating a framework for actual individualisation of care.

Keywords: Acute Pain; Anesthesia, Local; Pain Management.

Keywords: MRI and cancer; MRI surveillance; Neuromodulation; cancer screening.

Abstract
Virtual reality-delivered psychological therapies have recently been investigated as non-pharmacological management for acute and chronic pain. However, no virtual reality pain therapy software existed that met the needs of cancer patients with neuropathic pain. We created a bespoke virtual reality-delivered pain therapy software programme to help cancer patients manage neuropathic pain incorporating guided visualisation and progressive muscle relaxation techniques, whilst minimising the risk of cybersickness in this vulnerable patient population. This randomised controlled pilot study evaluated the feasibility, acceptability, recruitment rates and risk of cybersickness of this pain therapy software programme. Clinical outcomes including opioid consumption, pain severity, pain interference and global quality of life scores were secondary aims. Of 87 eligible cancer patients with neuropathic pain, 39 were recruited (47%), allocated to either the intervention (20 patients, virtual reality pain therapy software programme) or control (19 patients, viewing virtual reality videos). Four patients withdrew before the 3-month follow-up (all in the control group). Pre-existing dizziness (Spearman ρ 0.37, p = 0.02) and pre-existing nausea (Spearman ρ 0.81, p < 0.001) were significantly associated with risk of cybersickness in both groups. Patients in the intervention group reported less cybersickness, as well as tolerated and completed all therapy sessions. At 1- and 3-month follow-up, there were trends in the intervention group towards reductions in: oral morphine equivalent daily dose opioid consumption (-8 mg and -4 mg; vs. control: 0 mg and +15 mg respectively); modified Brief Pain Inventory pain severity (-0.4, -0.8; vs. control +0.4, -0.3); and pain interference (-0.9, -1.8; vs. control -0.2, -0.3) scores. The global quality of life subscale from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 was not significantly changed between groups at 1 and 3 months (intervention: -5, -8; vs. control: +3, +4). This newly created virtual reality-delivered pain therapy software programme was shown to be feasible and acceptable to cancer patients with neuropathic pain. These results will aid the design of a definitive multicentre randomised controlled trial.

Abstract
This preclinical systematic review aimed to determine the effectiveness of different types and doses of exercise on pain behaviour and biomarkers in preclinical models of focal neuropathic pain. We searched MEDLINE, EMBASE, Web of Science, PubMed, SCOPUS, CINAHL and Cochrane library from inception to November 2022 for preclinical studies evaluating the effect of exercise compared to control interventions on neuropathic pain behaviour after experimental sciatic nerve injury. If possible, data were meta-analysed using random effect models with inverse-variance weighting. Thirty-seven studies were included and 26 meta-analysed. Risk of bias (SYRCLE tool) remained unclear in most studies and reporting quality (CAMARADES) was variable. Exercise reduced mechanical (SMD 0.53 (95% CI 0.31, 0.74), p= 0.0001, I2=0%, n=364), heat (0.32 (0.07,0.57), p=0.01, I2=0%, n=266) and cold hypersensitivity (0.51 (0.03, 1.0), p=0.04, I2=0%, n=90) compared to control interventions. No relationship was apparent between exercise duration or intensity and antinociception. Exercise modulated biomarkers related to different systems (e.g., immune system, neurotrophins). Whereas firm conclusions are prevented by the use of male animals only, variable reporting quality and unclear risk of bias in many studies, our results suggest that aerobic exercise is a promising tool in the management of focal neuropathic pain. Registration PROSPERO CRD42021231286. Perspective: This systematic review and meta-analysis demonstrates that aerobic exercise reduces neuropathic pain-related behavior in preclinical models of sciatic nerve injury. This effect is accompanied by changes in biomarkers associated with inflammation and neurotrophins among others. These results could help to develop exercise interventions for patients with neuropathic pain.

Abstract
Purpose: Postamputation pain is challenging because of complex mechanisms involving a multitude of pain pathways and psychological factors. This patient population also tends to have extensive comorbidities with or without a background of chronic pain. Electrical neuromodulation such as peripheral nerve stimulation has gained traction in the realm of chronic pain. Recently, the off-label use of hybrid perineural nerve stimulation in combination with locoregional block via the stimulating nerve block catheter has been described in single-center case reports.

Clinical features: Herein, we present a case series of six patients from two different Canadian hospitals using such a hybrid technique in three different clinical scenarios. These scenarios were (1) local anesthetic dose minimization in the presence of multiple nerve block catheters, (2) analgesia augmentation when local anesthetic alone is insufficient, and (3) provision of an analgesic adjunct as part of a multimodal regimen. A stimulating sciatic nerve block catheter was inserted under ultrasound and nerve stimulation guidance for these cases. Patients tended to experience pain on the subsequent postoperative days whereby the off-label use of nerve stimulation successfully reduced their pain score and stabilized or decreased their opioid consumption or minimized the need to increase the local anesthetic dose when doing so could have precipitated local anesthetic toxicity.

Conclusion: Our case series supports the feasibility of using a combination of low-frequency perineural stimulation and local anesthetic infusion via a single perineural nerve block catheter to manage challenging postamputation pain.

Objectives: Anodal transcranial direct current stimulation (tDCS) of primary motor cortex (M1) and cathodal of the primary sensory cortex (S1) have previously shown to modulate the sensory thresholds when administered with the reference electrode located over the contralateral supraorbital area (SO). Combining the two stimulation paradigms into one with simultaneous stimulation of the two brain areas (M1 + S1 - tDCS) may result in a synergistic effect inducing a prominent neuromodulation, noticeable in the pain thresholds. The aim of this study is to assess the efficacy of the novel M1 + S1 - tDCS montage compared to sham-stimulation in modulating the pain thresholds in healthy adults.

Methods: Thirty-nine (20 males) subjects were randomly assigned to either receiving 20 min. active M1 + S1 - tDCS or sham tDCS in a double-blinded single session study. Thermal and mechanical pain thresholds were assessed before and after the intervention.

Results: There were no significant differences in the pain thresholds within either group, or between the M1 + S1 - tDCS group and the Sham-tDCS group (p>0.05), indicating that the intervention was ineffective in inducing a neuromodulation of the somatosensory system.

Conclusions: Experimental investigations of novel tDCS electrode montages, that are scientifically based on existing studies or computational modelling, are essential to establish better tDCS protocols. Here simultaneous transcranial direct current stimulation of the primary motor cortex and primary sensory cortex showed no effect on the pain thresholds of the neck musculature in healthy subjects. This tDCS montage may have been ineffective due to how the electrical field reaches the targeted neurons, or may have been limited by the design of a single tDCS administration. The study adds to the existing literature of the studies investigating effects of new tDCS montages with the aim of establishing novel non-invasive brain stimulation interventions for chronic neck pain rehabilitation. North Denmark Region Committee on Health Research Ethics (VN-20180085) ClinicalTrials.gov (NCT04658485).

Pain is highly prevalent and pharmacological therapy is not always efficacious. There are a few pathophysiological reasons to believe that neuromodulation would increase the rate of success of pain management. This review article is focused on that aspect, discussing non-invasive or minimally invasive neuromodulation techniques in both the inpatient and outpatient setting. This article provides an in-depth discussion of the multiple neuromodulation techniques available over time to be suitable and effective when used as analgesic therapies for chronic pain. We reviewed the literature and discussed all available neuromodulation options that were tested in the inpatient and outpatient setting. Neuromodulation plays a very important role in treating chronic pain in both inpatient and outpatient setting.

Potassium homeostasis is fundamental for brain function. Therefore, effective removal of excessive K+ from the synaptic cleft during neuronal activity is paramount. Astrocytes play a key role in K+ clearance from the extracellular milieu using various mechanisms, including uptake via Kir channels and the Na+-K+ ATPase, and spatial buffering through the astrocytic gap-junction coupled network. Recently we showed that alterations in the concentrations of extracellular potassium ([K+]o) or impairments of the astrocytic clearance mechanism affect the resonance and oscillatory behavior of both the individual and networks of neurons. These results indicate that astrocytes have the potential to modulate neuronal network activity, however, the cellular effectors that may affect the astrocytic K+ clearance process are still unknown. In this study, we have investigated the impact of neuromodulators, which are known to mediate changes in network oscillatory behavior, on the astrocytic clearance process. Our results suggest that while some neuromodulators (5-HT; NA) might affect astrocytic spatial buffering via gap-junctions, others (DA; Histamine) primarily affect the uptake mechanism via Kir channels. These results suggest that neuromodulators can affect network oscillatory activity through parallel activation of both neurons and astrocytes, establishing a synergistic mechanism to maximize the synchronous network activity.

Epilepsy affects approximately 70 million people worldwide, and it is a significant contributor to the global burden of neurological disorders. Despite the advent of new AEDs, drug resistant-epilepsy continues to affect 30-40% of PWE. Once identified as having drug-resistant epilepsy, these patients should be referred to a comprehensive epilepsy center for evaluation to establish if they are candidates for potential curative surgeries. Unfortunately, a large proportion of patients with drug-resistant epilepsy are poor surgical candidates due to a seizure focus located in eloquent cortex, multifocal epilepsy or inability to identify the zone of ictal onset. An alternative treatment modality for these patients is neuromodulation. Here we present the evidence, indications and safety considerations for the neuromodulation therapies in vagal nerve stimulation (VNS), responsive neurostimulation (RNS), or deep brain stimulation (DBS).

The journal Pain Medicine published a supplement in 2019 on the theme of Neuromodulation in relation to the spine and nervous system.

Anaesthesia is the official journal of the Association of Anaesthetists of Great Britain and Ireland and is international in scope and comprehensive in coverage. It publishes original, peer-reviewed articles on all aspects of general and regional anaesthesia, intensive care and pain therapy, including research on equipment.

Published monthly by the International Anesthesia Research Society (IARS) and includes peer-reviewed, original clinical and research articles, providing practicing physicians, researchers and allied medical personnel in anaesthesiology and related fields with a wealth of information to keep them up-to-date with the latest issues and advances in the field.

Anesthesiology is the official Journal of the American Society of Anesthesiologists. The Journal published its first issue in July 1940. The Journal receives nearly 1500 manuscript submissions per year, and publishes almost 4000 pages (about 3,000,000 words) of peer-reviewed material annually. Over 50% of the submissions and more than 6000 of its subscribers are from outside the United States, making it a major international publication.

A well-established journal in the field of behavioural and cognitive neuroscience, Behavioral and Brain Functions welcomes manuscripts which provide insight into the neurobiological mechanisms underlying behaviour and brain function, or dysfunction. The journal gives priority to manuscripts that combine both neurobiology and behaviour in a non-clinical manner.

Founded in 1923, the British Journal of Anaesthesia (BJA) remains the oldest and largest independent journal of anaesthesia. The journal strives to support research and discovery in the field by publishing the best original articles in all branches of Anaesthesia.

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The scope of Brain Stimulation extends across the entire field of brain stimulation, including noninvasive and invasive techniques and technologies that alter brain function through the use of electrical, magnetic, radiowave, or focally targeted pharmacologic stimulation. This includes investigations that study the effects of brain stimulation on basic processes, such as gene expression and other aspects of molecular biology, neurochemical regulation, functional brain activity, sensorimotor function, and cognitive and affective processes at the systems level.

Child Neurology Open (CNO) is an interdisciplinary, peer-reviewed, open access forum for the most current information from clinical and investigative studies in the wide field of clinical pediatric neuroscience. Published articles come from a variety of disciplines, including child neurology, pediatric neurosurgery, pediatric neuroradiology, child and adolescent psychiatry, pediatric neuropsychology, developmental and behavioral pediatrics, and developmental neurobiology. Following careful peer review of submitted material, subsequent acceptance results in very rapid online publication and indexing in the major scientific publication databases.

The Clinical Journal of Pain explores all aspects of pain and its effective treatment, bringing you the insights of leading anesthesiologists, surgeons, internists, neurologists, orthopedists, psychiatrists and psychologists, clinical pharmacologists, and physical and rehabilitation therapists.

A multi-disciplinary, international journal that aims to be a global forum on all aspects of pain research and pain management. The journal publishes clinical and basic science research papers relevant to all aspects of pain and its management.

Frontiers in Neuroscience is a leading journal in its field, publishing rigorously peer-reviewed research across a wide spectrum of specialties and disciplines.

Human Brain Mapping publishes peer-reviewed basic, clinical, technical, and theoretical research in the interdisciplinary and rapidly expanding field of human brain mapping.

Interdisciplinary Neurosurgery: Advanced Techniques and Case Management is an open access journal, devoted to the publication of manuscripts of original work and review articles in the field of interdisciplinary neurosurgery, promoting excellence and advances in complex neurosurgical situations pioneering neurosurgical techniques , including case series and technical notes.

The Journal of Neurorestoratology is an international, peer-reviewed, open access journal focusing on original experimental and clinical research, methodological advances, neurorestorative mechanisms’ exploring, and expert reviews in the field of Neurorestoratology. Clinical studies on geriatric, pediatric, hereditary and traumatic disorders in central nervous system are of particular interest. And welcome neurorestorative strategies' exploring, which involve cell therapy, tissue engineering or bioengineering, neuromodulation by electro-magnetic stimulation, neural prostheses or brain-machine interface, pharmacotherapy or chemical therapies, neurorestorative surgery, active rehabilitation training, others, and combinations of these strategies.

Neurobiology of Pain is an international journal for the publication of basic and translational research on the mechanisms of acute and chronic pain. It focuses on experimental studies of pain mechanisms at every level from molecular and cellular to brain imaging and behavioural.

Neuroethics is a forum for interdisciplinary studies in neuroethics and related issues in the sciences of the mind. The focus is on ethical issues posed by new technologies developed via neuroscience, such as psycho-pharmaceuticals and other ways of intervening in the mind and the practice of neuroscience itself. This important publication covers the dual areas of neuroethics: the ethics of neuroscience and the neuroscience of ethics. It offers comprehensive bibliographies, reviews of significant literature, information on activities including partial proceedings of selected meetings, and an opinions section for reader commentaries.

NeuroImage: Clinical, a journal of diseases, disorders and syndromes involving the Nervous System, provides a vehicle for communicating important advances in the study of abnormal structure-function relationships of the human nervous system based on imaging.

Neurological Sciences and Neurophysiology is the double blind peer-reviewed, open access, online only, international publication organ of Turkish Society of Clinical Neurophysiology EEG-EMG. The journal is a quarterly publication, published in March, June, September and December and the publication language of the journal is English. Neurological Sciences and Neurophysiology aims to contribute to the international literature by publishing original clinical and experimental research articles, review articles, and letters to the editor on all fields of neurological sciences and especially in neurophysiology. The journal is directed at an audience of physicians and scientists of Neurology, Neurosurgery, Psychiatry, Neurophysiology, Neuropathology, Neuroradiology.

In recognition of the belief that the future for dissemination of scientific and medical research lies in open access on-line journals, Neurology International has been developed as a forum for the free and open international exchange of progress in the clinical neurosciences. By adhering to standards for high quality and ethics, Neurology International offers a unique service to the world's medical community. The international board of editors for the journal are committed to promoting scientific advancement and excellence for the benefit of all, in all aspects of neurology, as well as diagnosis and treatment of stroke, Alzheimer disease, epilepsy, Parkinson disease, multiple sclerosis, and other disorders of the brain and nervous system.

Neurology Research International is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies focusing on diseases of the nervous system, as well as normal neurological functioning. The journal will consider basic, translational, and clinical research, including animal models and clinical trials.

Neuromodulation: Technology at the Neural Interface is the preeminent journal in the area of neuromodulation, providing our readership with the state of the art clinical, translational and basic science research in our field and representing the needs of the broad neuromodulation community. For clinicians, engineers, scientists and members of the biotechnology industry alike, Neuromodulation provides timely and rigorously peer reviewed articles on the technology, science and clinical application of devices that interface with the nervous system to treat disease and improve function. Neuromodulation covers an ever expanding field including pain, headache, movement disorders, spasticity, paralysis, psychiatric disorders, epilepsy, sensory deprivation, gastric dysfunction, obesity and incontinence.

The mission of Neuronal Signaling is to provide an interdisciplinary home for neuroscientific disciplines covering all aspects of in vitro and in vivo signaling from cell to brain in health and disease. Relevant topics range from signaling pathways involved in nervous system development and normal physiology through to neurodegenerative, neurological and psychiatric disorders and other pathologies.

PAIN® is the official publication of the International Association for the Study of Pain® (IASP®). PAIN® publishes original research on the nature, mechanisms, and treatment of pain and provides a multidisciplinary forum for the dissemination of research in the basic and clinical sciences.

Pain Medicine is dedicated to pain clinicians, educators, and researchers with an interest in pain from various medical specialties and related health disciplines. The journal reflects the rapid growth in pain science and practice, as well as the field's need for policy, ethical, and forensic commentary on pain and its management. It promotes the visibility and development of pain medicine as a worldwide interdisciplinary medical specialty within a collaborative, multidisciplinary pain field.

A peer-reviewed, multi-disciplinary journal written by and directed to an audience of interventional pain physicians, clinicians and basic scientists with an interest in interventional pain management and pain medicine.

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World Neurosurgery: X offers authors with high-quality research who want to publish in a gold open access journal the opportunity to make their work immediately, permanently, and freely accessible.