Editorial

3 pages, 169 KiB

Open AccessEditorial

by Alexander L. Green and Tipu Z. Aziz

Brain Sci. 2020, 10(5), 267; https://doi.org/10.3390/brainsci10050267 - 30 Apr 2020

Cited by 1 | Viewed by 1884

Over 7% of the Western population suffer from intractable pain and despite pharmacotherapy, many patients’ pain is refractory [...] Full article

(This article belongs to the Special Issue Neuromodulation for Intractable Pain)

Research

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13 pages, 2929 KiB

Open AccessFeature PaperArticle

Dorsal Root Ganglion Stimulation Modulates Cortical Gamma Activity in the Cognitive Dimension of Chronic Pain

by Tariq Parker, Yongzhi Huang, Ashley L.B. Raghu, James J. FitzGerald, Alexander L. Green and Tipu Z. Aziz

Brain Sci. 2020, 10(2), 95; https://doi.org/10.3390/brainsci10020095 - 11 Feb 2020

Cited by 16 | Viewed by 3029

Abstract

A cognitive task, the n-back task, was used to interrogate the cognitive dimension of pain in patients with implanted dorsal root ganglion stimulators (DRGS). Magnetoencephalography (MEG) signals from thirteen patients with implanted DRGS were recorded at rest and while performing the n-back task [...] Read more.

A cognitive task, the n-back task, was used to interrogate the cognitive dimension of pain in patients with implanted dorsal root ganglion stimulators (DRGS). Magnetoencephalography (MEG) signals from thirteen patients with implanted DRGS were recorded at rest and while performing the n-back task at three increasing working memory loads with DRGS-OFF and the task repeated with DRGS-ON. MEG recordings were pre-processed, then power spectral analysis and source localization were conducted. DRGS resulted in a significant reduction in reported pain scores (mean 23%, p = 0.001) and gamma oscillatory activity (p = 0.036) during task performance. DRGS-induced pain relief also resulted in a significantly reduced reaction time during high working memory load (p = 0.011). A significant increase in average gamma power was observed during task performance compared to the resting state. However, patients who reported exacerbations of pain demonstrated a significantly elevated gamma power (F(3,80) = 65.011612, p < 0.001, adjusted p-value = 0.01), compared to those who reported pain relief during the task. Our findings demonstrate that gamma oscillatory activity is differentially modulated by cognitive load in the presence of pain, and this activity is predominantly localized to the prefrontal and anterior cingulate cortices in a chronic pain cohort. Full article

(This article belongs to the Special Issue Neuromodulation for Intractable Pain)

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12 pages, 2191 KiB

Open AccessArticle

Manual Therapy Reduces Pain Behavior and Oxidative Stress in a Murine Model of Complex Regional Pain Syndrome Type I

by Afonso S. I. Salgado, Juliana Stramosk, Daniela D. Ludtke, Ana C. C. Kuci, Daiana C. Salm, Lisandro A. Ceci, Fabricia Petronilho, Drielly Florentino, Lucineia G. Danielski, Aline Gassenferth, Luana R. Souza, Gislaine T. Rezin, Adair R. S. Santos, Leidiane Mazzardo-Martins, William R. Reed and Daniel F. Martins

Brain Sci. 2019, 9(8), 197; https://doi.org/10.3390/brainsci9080197 - 10 Aug 2019

Cited by 14 | Viewed by 4659

Abstract

Complex regional pain syndrome type I (CRPS-I) is a chronic painful condition. We investigated whether manual therapy (MT), in a chronic post-ischemia pain (CPIP) model, is capable of reducing pain behavior and oxidative stress. Male Swiss mice were subjected to ischemia-reperfusion (IR) to [...] Read more.

Complex regional pain syndrome type I (CRPS-I) is a chronic painful condition. We investigated whether manual therapy (MT), in a chronic post-ischemia pain (CPIP) model, is capable of reducing pain behavior and oxidative stress. Male Swiss mice were subjected to ischemia-reperfusion (IR) to mimic CRPS-I. Animals received ankle joint mobilization 48h after the IR procedure, and response to mechanical stimuli was evaluated. For biochemical analyses, mitochondrial function as well as oxidative stress thiobarbituric acid reactive substances (TBARS), protein carbonyls, antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) levels were determined. IR induced mechanical hyperalgesia which was subsequently reduced by acute MT treatment. The concentrations of oxidative stress parameters were increased following IR with MT treatment preventing these increases in malondialdehyde (MDA) and carbonyls protein. IR diminished the levels of SOD and CAT activity and MT treatment prevented this decrease in CAT but not in SOD activity. IR also diminished mitochondrial complex activity, and MT treatment was ineffective in preventing this decrease. In conclusion, repeated sessions of MT resulted in antihyperalgesic effects mediated, at least partially, through the prevention of an increase of MDA and protein carbonyls levels and an improvement in the antioxidant defense system. Full article

(This article belongs to the Special Issue Neuromodulation for Intractable Pain)

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11 pages, 1584 KiB

Open AccessArticle

Upregulation of IL-1 Receptor Antagonist in a Mouse Model of Migraine

by Salvo Danilo Lombardo, Emanuela Mazzon, Maria Sofia Basile, Eugenio Cavalli, Placido Bramanti, Riccardo Nania, Paolo Fagone, Ferdinando Nicoletti and Maria Cristina Petralia

Brain Sci. 2019, 9(7), 172; https://doi.org/10.3390/brainsci9070172 - 19 Jul 2019

Cited by 26 | Viewed by 4738

Abstract

Migraine is a disorder characterized by attacks of monolateral headaches, often accompanied by nausea, vomiting, and photophobia. Around 30% of patients also report aura symptoms. The cause of the aura is believed to be related to the cortical spreading depression (CSD), a wave [...] Read more.

Migraine is a disorder characterized by attacks of monolateral headaches, often accompanied by nausea, vomiting, and photophobia. Around 30% of patients also report aura symptoms. The cause of the aura is believed to be related to the cortical spreading depression (CSD), a wave of neuronal and glial depolarization originating in the occipital cortex, followed by temporary neuronal silencing. During a migraine attack, increased expression of inflammatory mediators, along with a decrease in the expression of anti-inflammatory genes, have been observed. The aim of this study was to evaluate the expression of inflammatory genes, in particular that of IL-1 receptor antagonist (IL-1RN), following CSD in a mouse model of familial hemiplegic migraine type 1 (FHM-1). We show here that the expression of IL-1RN was upregulated after the CSD, suggesting a possible attempt to modulate the inflammatory response. This study allows researchers to better understand the development of the disease and aids in the search for new therapeutic strategies in migraine. Full article

(This article belongs to the Special Issue Neuromodulation for Intractable Pain)

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12 pages, 7179 KiB

Open AccessArticle

Applying a Sensing-Enabled System for Ensuring Safe Anterior Cingulate Deep Brain Stimulation for Pain

by Yongzhi Huang, Binith Cheeran, Alexander L. Green, Timothy J. Denison and Tipu Z. Aziz

Brain Sci. 2019, 9(7), 150; https://doi.org/10.3390/brainsci9070150 - 26 Jun 2019

Cited by 13 | Viewed by 4055

Abstract

Deep brain stimulation (DBS) of the anterior cingulate cortex (ACC) was offered to chronic pain patients who had exhausted medical and surgical options. However, several patients developed recurrent seizures. This work was conducted to assess the effect of ACC stimulation on the brain [...] Read more.

Deep brain stimulation (DBS) of the anterior cingulate cortex (ACC) was offered to chronic pain patients who had exhausted medical and surgical options. However, several patients developed recurrent seizures. This work was conducted to assess the effect of ACC stimulation on the brain activity and to guide safe DBS programming. A sensing-enabled neurostimulator (Activa PC + S) allowing wireless recording through the stimulating electrodes was chronically implanted in three patients. Stimulation patterns with different amplitude levels and variable ramping rates were tested to investigate whether these patterns could provide pain relief without triggering after-discharges (ADs) within local field potentials (LFPs) recorded in the ACC. In the absence of ramping, AD activity was detected following stimulation at amplitude levels below those used in chronic therapy. Adjustment of stimulus cycling patterns, by slowly ramping on/off (8-s ramp duration), was able to prevent ADs at higher amplitude levels while maintaining effective pain relief. The absence of AD activity confirmed from the implant was correlated with the absence of clinical seizures. We propose that AD activity in the ACC could be a biomarker for the likelihood of seizures in these patients, and the application of sensing-enabled techniques has the potential to advance safer brain stimulation therapies, especially in novel targets. Full article

(This article belongs to the Special Issue Neuromodulation for Intractable Pain)

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20 pages, 270 KiB

Open AccessArticle

Neurostimulation for Intractable Chronic Pain

by Timothy R. Deer, Sameer Jain, Corey Hunter and Krishnan Chakravarthy

Brain Sci. 2019, 9(2), 23; https://doi.org/10.3390/brainsci9020023 - 24 Jan 2019

Cited by 51 | Viewed by 9396

Abstract

The field of neuromodulation has seen unprecedented growth over the course of the last decade with novel waveforms, hardware advancements, and novel chronic pain indications. We present here an updated review on spinal cord stimulation, dorsal root ganglion stimulation, and peripheral nerve stimulation. [...] Read more.

The field of neuromodulation has seen unprecedented growth over the course of the last decade with novel waveforms, hardware advancements, and novel chronic pain indications. We present here an updated review on spinal cord stimulation, dorsal root ganglion stimulation, and peripheral nerve stimulation. We focus on mechanisms of action, clinical indications, and future areas of research. We also present current drawbacks with current stimulation technology and suggest areas of future advancements. Given the current shortage of viable treatment options using a pharmacological based approach and conservative interventional therapies, neuromodulation presents an interesting area of growth and development for the interventional pain field and provides current and future practitioners a fresh outlook with regards to its place in the chronic pain treatment paradigm. Full article

(This article belongs to the Special Issue Neuromodulation for Intractable Pain)

Review

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19 pages, 347 KiB

Open AccessReview

The Use of Neuromodulation for Symptom Management

by Sarah Marie Farrell, Alexander Green and Tipu Aziz

Brain Sci. 2019, 9(9), 232; https://doi.org/10.3390/brainsci9090232 - 12 Sep 2019

Cited by 4 | Viewed by 3097

Abstract

Pain and other symptoms of autonomic dysregulation such as hypertension, dyspnoea and bladder instability can lead to intractable suffering. Incorporation of neuromodulation into symptom management, including palliative care treatment protocols, is becoming a viable option scientifically, ethically, and economically in order to relieve [...] Read more.

Pain and other symptoms of autonomic dysregulation such as hypertension, dyspnoea and bladder instability can lead to intractable suffering. Incorporation of neuromodulation into symptom management, including palliative care treatment protocols, is becoming a viable option scientifically, ethically, and economically in order to relieve suffering. It provides further opportunity for symptom control that cannot otherwise be provided by pharmacology and other conventional methods. Full article

(This article belongs to the Special Issue Neuromodulation for Intractable Pain)

16 pages, 649 KiB

Open AccessReview

Neuromodulation for Pelvic and Urogenital Pain

by Holly Roy, Ifeoma Offiah and Anu Dua

Brain Sci. 2018, 8(10), 180; https://doi.org/10.3390/brainsci8100180 - 29 Sep 2018

Cited by 33 | Viewed by 9632

Abstract

Chronic pain affecting the pelvic and urogenital area is a major clinical problem with heterogeneous etiology, affecting both male and female patients and severely compromising quality of life. In cases where pharmacotherapy is ineffective, neuromodulation is proving to be a potential avenue to [...] Read more.

Chronic pain affecting the pelvic and urogenital area is a major clinical problem with heterogeneous etiology, affecting both male and female patients and severely compromising quality of life. In cases where pharmacotherapy is ineffective, neuromodulation is proving to be a potential avenue to enhance analgesic outcomes. However, clinicians who frequently see patients with pelvic pain are not traditionally trained in a range of neuromodulation techniques. The aim of this overview is to describe major types of pelvic and urogenital pain syndromes and the neuromodulation approaches that have been trialed, including peripheral nerve stimulation, dorsal root ganglion stimulation, spinal cord stimulation, and brain stimulation techniques. Our conclusion is that neuromodulation, particularly of the peripheral nerves, may provide benefits for patients with pelvic pain. However, larger prospective randomized studies with carefully selected patient groups are required to establish efficacy and determine which patients are likely to achieve the best outcomes. Full article

(This article belongs to the Special Issue Neuromodulation for Intractable Pain)

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19 pages, 273 KiB

Open AccessReview

The Current State of Deep Brain Stimulation for Chronic Pain and Its Context in Other Forms of Neuromodulation

by Sarah Marie Farrell, Alexander Green and Tipu Aziz

Brain Sci. 2018, 8(8), 158; https://doi.org/10.3390/brainsci8080158 - 20 Aug 2018

Cited by 50 | Viewed by 6989

Abstract

Chronic intractable pain is debilitating for those touched, affecting 5% of the population. Deep brain stimulation (DBS) has fallen out of favour as the centrally implantable neurostimulation of choice for chronic pain since the 1970–1980s, with some neurosurgeons favouring motor cortex stimulation as [...] Read more.

Chronic intractable pain is debilitating for those touched, affecting 5% of the population. Deep brain stimulation (DBS) has fallen out of favour as the centrally implantable neurostimulation of choice for chronic pain since the 1970–1980s, with some neurosurgeons favouring motor cortex stimulation as the ‘last chance saloon’. This article reviews the available data and professional opinion of the current state of DBS as a treatment for chronic pain, placing it in the context of other neuromodulation therapies. We suggest DBS, with its newer target, namely anterior cingulate cortex (ACC), should not be blacklisted on the basis of a lack of good quality study data, which often fails to capture the merits of the treatment. Full article

(This article belongs to the Special Issue Neuromodulation for Intractable Pain)

9 pages, 209 KiB

Open AccessReview

Spinal Cord Stimulation for Neuropathic Pain: Current Trends and Future Applications

by Ivano Dones and Vincenzo Levi

Brain Sci. 2018, 8(8), 138; https://doi.org/10.3390/brainsci8080138 - 24 Jul 2018

Cited by 54 | Viewed by 6831

Abstract

The origin and the neural pathways involved in chronic neuropathic pain are still not extensively understood. For this reason, despite the wide variety of pain medications available on the market, neuropathic pain is challenging to treat. The present therapeutic alternative considered as the [...] Read more.

The origin and the neural pathways involved in chronic neuropathic pain are still not extensively understood. For this reason, despite the wide variety of pain medications available on the market, neuropathic pain is challenging to treat. The present therapeutic alternative considered as the gold standard for many kinds of chronic neuropathic pain is epidural spinal cord stimulation (SCS). Despite its proved efficacy, the favourable cost-effectiveness when compared to the long-term use of poorly effective drugs and the expanding array of indications and technical improvements, SCS is still worldwide largely neglected by general practitioners, neurologists, neurosurgeons and pain therapists, often bringing to a large delay in considering as a therapeutic option for patients affected by neuropathic chronic pain. The present state of the art of SCS in the treatment of chronic neuropathic pain is here overviewed and speculations on whether to use a trial period or direct implant, to choose between percutaneous leads or paddle electrodes and on the pros and cons of the different patterns of stimulation presently available on the market (tonic stim, high-frequency stim and burst stim) are described. Full article

(This article belongs to the Special Issue Neuromodulation for Intractable Pain)

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