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Interest in deciphering the fundamental mechanisms and processes of the human mind represents a central driving force in modern neuroscience research. Activities in support of this goal rely on advanced methodologies and engineering systems that are capable of interrogating and stimulating neural pathways, from single cells in small networks to interconnections that span the entire brain. Recent research establishes the foundations for a broad range of creative neurotechnologies that enable unique modes of operation in this context. This review focuses on those systems with proven utility in animal model studies and with levels of technical maturity that suggest a potential for broad deployment to the neuroscience community in the relatively near future. We include a brief summary of existing and emerging neuroscience techniques, as background for a primary focus on device technologies that address associated opportunities in electrical, optical and microfluidic neural interfaces, some with multimodal capabilities. Examples of the use of these technologies in recent neuroscience studies illustrate their practical value. The vibrancy of the engineering science associated with these platforms, the interdisciplinary nature of this field of research and its relevance to grand challenges in the treatment of neurological disorders motivate continued growth of this area of study.
Learn More >Diabetic neuropathy (DN) is an early, common complication of diabetes mellitus (DM) leading to chronic pain, sensory loss and muscle atrophy. Due to its multifactorial etiology, neuron cultures have been proposed as simplified systems for DN studies. However, the most used models currently available do not recreate the chronic and systemic damage suffered by peripheral neurons of type-2 DM (T2DM) individuals. Here, we cultured neurons derived from dorsal root ganglia from 6-month-old diabetic db/db-mice, and evaluated their morphology by the Sholl method as an easy-to-analyze readout of neuronal function. We showed that neurons obtained from diabetic mice exhibited neuritic regeneration defects in basal culture conditions, compared to neurons from non-diabetic mice. Next, we evaluated the morphological response to common neuritogenic factors including NGF and laminin. Neurons derived from diabetic mice exhibited reduced regenerative responses to these factors compared to neurons from non-diabetic mice. Finally, we analyzed the neuronal response to a putative DN therapy based on the secretome of mesenchymal stem cells (MSC). Neurons from diabetic mice treated with MSC-secretome displayed a significant improvement in neuritic regeneration, but still reduced when compared to neurons derived from non-diabetic mice. This model recapitulates many alterations observed in sensory neurons of T2DM individuals, suggesting the possibility of studying neuronal functions without the need of adding additional toxic factors to culture plates. This model may be useful for evaluating intrinsic neuronal responses in a cell-autonomous manner, and as a throughput screening for the pre-evaluation of new therapies for DN.
Learn More >Cannabidiol (CBD) is the second most abundant component of the Cannabis plant and is known to have effects distinct from Δ -tetrahydrocannabinol (THC). Many studies that examined the behavioral effects of CBD concluded that it lacks the psychotomimetic effects attributed to THC. However, CBD was shown to have a broad spectrum of effects on several conditions such as anxiety, inflammation, neuropathic pain, and epilepsy. It is currently thought that CBD engages different targets and hence CBD's effects are thought to be due to multiple molecular mechanisms of action. A well-accepted set of targets include GPCRs and ion channels, with the serotonin 5-HT receptor and the transient receptor potential cation channel TRPV1 channel being the two main targets. CBD has also been thought to target G protein-coupled receptors (GPCRs) such as cannabinoid and opioid receptors. Other studies have suggested a role for additional GPCRs and ion channels as targets of CBD. Currently, the clinical efficacy of CBD is not completely understood. Evidence derived from randomized clinical trials, in vitro and in vivo models and real-world observations support the use of CBD as a drug treatment option for anxiety, neuropathy, and many other conditions. Hence an understanding of the current status of the field as it relates to the targets for CBD is of great interest so, in this review, we include findings from recent studies that highlight these main targets.
Learn More >Pain in fibromyalgia (FM) and chronic fatigue syndrome (CFS) is assumed to originate from central sensitization. Perineural cysts or Tarlov cysts (TCs) are nerve root dilations resulting from pathologically increased cerebrospinal fluid pressure. These cysts initially affect sensory neurons and axons in dorsal root ganglia and produce sensory symptoms (pain and paresthesia). Symptomatic TC (STC) patients often complain about widespread pain and fatigue. Consequently, STC patients may initially be diagnosed with FM, CFS, or both. The objective of this study was to document the prevalence of TCs in patients diagnosed with FM or CFS.
Learn More >Transient receptor potential melastatin 8 (TRPM8) channels play a central role in the detection of environmental cold temperatures in the somatosensory system. TRPM8 is found in a subset of unmyelinated (C-type) afferents located in the dorsal root (DRG) and trigeminal ganglion (TG). Cold hypersensitivity is a common symptom of neuropathic pain conditions caused by cancer therapy, spinal cord injury, viral infection, multiple sclerosis, diabetes, or withdrawal symptoms associated with chronic morphine treatment. Therefore, TRPM8 has received great attention as a therapeutic target. However, as the activity of TRPM8 is unique in sensing cool temperature as well as warming, it is critical to understand the signaling transduction pathways that control modality-specific activity of TRPM8 in healthy versus pathological settings. This review summarizes recent advances in our understanding of the mechanisms involved in the regulation of the TRPM8 activity.
Learn More >Neck pain is a leading cause of years lived with disability and is often managed with opioid medications in primary care settings, though this is contraindicated by national guidelines. The aim of this study was to determine the prevalence of opioid prescription for neck pain at a primary care visit and to analyze the geographic variation and trends in opioid prescriptions between 2011 and 2017.
Learn More >Chronic nonmalignant pain, sleep disturbances and sleep disorders are highly prevalent conditions among U.S. military veterans. Evidence summaries highlight the influence of sleep on pain outcomes in the general adult population but not for the military veteran population. This is a significant gap as U.S. military veterans are an exceedingly high-risk population for both chronic pain and sleep disturbances and/or disorders. We aimed to review the influence of sleep disturbances and sleep disorders on pain outcomes among veterans with chronic nonmalignant pain. A systematic scoping review was conducted using PubMed/Medline, EMBASE, Scopus, CINAHL, and PsycINFO. Twenty-six out of 1450 studies from initial search were included in this review resulting in a combined sample size of N = 923,434 participants. Sleep disturbances and sleep disorders were associated with worse pain outcomes among veterans with chronic pain. Treatment-induced sleep improvements ameliorated pain outcomes in veterans with sleep disorders and sleep disturbances. Research is indicated to address an overlooked pain treatment opportunity – that of sleep disturbance and sleep disorder management.
Learn More >Patients with chronic musculoskeletal pain (CMP) have difficulty estimating their level of physical activity (PA). Factors associated with this difficulty have yet to be identified; however, identification could allow for increased accuracy in large-scale PA surveys, and enhanced self-management. The purpose of this study was to determine the relationship of interoception and alexithymia with differences between self-reported and objectively measured PA, and investigate factors as they relate to accurately self-reporting PA.
Learn More >This study compared the efficacy and safety of controlled-release pregabalin (GLA5PR GLARS-NF1 tablets) with those of an immediate-release pregabalin capsule after 12 weeks' administration to patients with peripheral neuropathic pain.
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