Chemo- and Optogenetic Strategies for the Elucidation of Pain Pathways

2019 ◽  
pp. 816-832 ◽  
Author(s):  
Sascha R. A. Alles ◽  
Anne-Marie Malfait ◽  
Richard J. Miller
Keyword(s):  
Chronic Pain ◽  
Pain Response ◽  
Conscious Perception ◽  
Novel Therapies ◽  
The Past ◽  
Nociceptive Pathways ◽  
Pain Pathways ◽  
Technical Advances ◽  
The Brain

Pain is not a simple phenomenon and, beyond its conscious perception, involves circuitry that allows the brain to provide an affective context for nociception, which can influence mood and memory. In the past decade, neurobiological techniques have been developed that allow investigators to elucidate the importance of particular groups of neurons in different aspects of the pain response, something that may have important translational implications for the development of novel therapies. Chemo- and optogenetics represent two of the most important technical advances of recent times for gaining understanding of physiological circuitry underlying complex behaviors. The use of these techniques for teasing out the role of neurons and glia in nociceptive pathways is a rapidly growing area of research. The major findings of studies focused on understanding circuitry involved in different aspects of nociception and pain are highlighted in this article. In addition, attention is drawn to the possibility of modification of chemo- and optogenetic techniques for use as potential therapies for treatment of chronic pain disorders in human patients.

scholarly journals The Microbiota–Gut–Brain Axis and Alzheimer Disease. From Dysbiosis to Neurodegeneration: Focus on the Central Nervous System Glial Cells

2021 ◽  
Vol 10 (11) ◽  
pp. 2358
Author(s):  
Maria Grazia Giovannini ◽  
Daniele Lana ◽  
Chiara Traini ◽  
Maria Giuliana Vannucchi
Keyword(s):  
Alzheimer Disease ◽  
Glial Cells ◽  
Cell Types ◽  
The Past ◽  
The Central Nervous System ◽  
Diseased State ◽  
The Brain ◽  
Alzheimer Disease Pathogenesis ◽  
Brain Homeostasis

The microbiota–gut system can be thought of as a single unit that interacts with the brain via the “two-way” microbiota–gut–brain axis. Through this axis, a constant interplay mediated by the several products originating from the microbiota guarantees the physiological development and shaping of the gut and the brain. In the present review will be described the modalities through which the microbiota and gut control each other, and the main microbiota products conditioning both local and brain homeostasis. Much evidence has accumulated over the past decade in favor of a significant association between dysbiosis, neuroinflammation and neurodegeneration. Presently, the pathogenetic mechanisms triggered by molecules produced by the altered microbiota, also responsible for the onset and evolution of Alzheimer disease, will be described. Our attention will be focused on the role of astrocytes and microglia. Numerous studies have progressively demonstrated how these glial cells are important to ensure an adequate environment for neuronal activity in healthy conditions. Furthermore, it is becoming evident how both cell types can mediate the onset of neuroinflammation and lead to neurodegeneration when subjected to pathological stimuli. Based on this information, the role of the major microbiota products in shifting the activation profiles of astrocytes and microglia from a healthy to a diseased state will be discussed, focusing on Alzheimer disease pathogenesis.

scholarly journals Optogenetics and photopharmacology in pain research and therapeutics

STEMedicine ◽  
2020 ◽  
Vol 1 (3) ◽  
pp. e43 ◽  
Author(s):  
Federico Iseppon ◽  
Manuel Arcangeletti
Keyword(s):  
Chronic Pain ◽  
Pain Treatment ◽  
Molecular Switches ◽  
Genetic Profiling ◽  
Pain Research ◽  
Recent Advances ◽  
Cellular Components ◽  
The Brain

Pain afflicts billions of people worldwide, who suffer especially from long-term chronic pain. This gruelling condition affects the nervous system at all levels: from the brain to the spinal cord, the Dorsal Root Ganglia (DRG) and the peripheral fibres innervating the skin. The nature of the different molecular and cellular components of the somatosensory modalities, as well as the complexity of the peripheral and central circuitry are yet poorly understood. Light-based techniques such as optogenetics, in concert with the recent advances in single-cell genetic profiling, can help to elucidate the role of diverse neuronal sub-populations in the encoding of different sensory and painful stimuli by switching these neurons on and off via optically active proteins, namely opsins.  Recently, photopharmacology has emerged from the efforts made to advance optogenetics. The introduction of azo-benzene-based light-sensitive molecular switches has been applied to a wide variety of molecular targets, from ion channels and receptors to transporters, enzymes and many more, some of which are paramount for pain research and therapy. In this Review, we summarise the recent advances in the fields of optogenetics and photopharmacology and we discuss the use of light-based techniques for the study of acute and chronic pain physiology, as well as their potential for future therapeutic use to improve pain treatment.

scholarly journals Neural Control of Immunity in Hypertension: Council on Hypertension Mid Career Award for Research Excellence, 2019

Hypertension ◽  
2020 ◽  
Vol 76 (3) ◽  
pp. 622-628
Author(s):  
Daniela Carnevale
Keyword(s):  
Immune Response ◽  
Nervous System ◽  
Neural Control ◽  
Neural Signals ◽  
The Past ◽  
Target Organs ◽  
Long Time ◽  
The Common ◽  
The Brain

The nervous system and the immune system share the common ability to exert gatekeeper roles at the interfaces between internal and external environment. Although interaction between these 2 evolutionarily highly conserved systems has been recognized for long time, the investigation into the pathophysiological mechanisms underlying their crosstalk has been tackled only in recent decades. Recent work of the past years elucidated how the autonomic nervous system controls the splenic immunity recruited by hypertensive challenges. This review will focus on the neural mechanisms regulating the immune response and the role of this neuroimmune crosstalk in hypertension. In this context, the review highlights the components of the brain-spleen axis with a focus on the neuroimmune interface established in the spleen, where neural signals shape the immune response recruited to target organs of high blood pressure.

scholarly journals Impaired Mitophagy in Neurons and Glial Cells during Aging and Age-Related Disorders

2021 ◽  
Vol 22 (19) ◽  
pp. 10251
Author(s):  
Vladimir Sukhorukov ◽  
Dmitry Voronkov ◽  
Tatiana Baranich ◽  
Natalia Mudzhiri ◽  
Alina Magnaeva ◽  
...  
Keyword(s):  
Glial Cells ◽  
Brain Aging ◽  
Cellular Level ◽  
Aging Brain ◽  
The Past ◽  
Age Related ◽  
Accumulation Of Damage ◽  
Quantity Control ◽  
The Brain

Aging is associated with a decline in cognitive function, which can partly be explained by the accumulation of damage to the brain cells over time. Neurons and glia undergo morphological and ultrastructure changes during aging. Over the past several years, it has become evident that at the cellular level, various hallmarks of an aging brain are closely related to mitophagy. The importance of mitochondria quality and quantity control through mitophagy is highlighted by the contribution that defects in mitochondria–autophagy crosstalk make to aging and age-related diseases. In this review, we analyze some of the more recent findings regarding the study of brain aging and neurodegeneration in the context of mitophagy. We discuss the data on the dynamics of selective autophagy in neurons and glial cells during aging and in the course of neurodegeneration, focusing on three mechanisms of mitophagy: non-receptor-mediated mitophagy, receptor-mediated mitophagy, and transcellular mitophagy. We review the role of mitophagy in neuronal/glial homeostasis and in the molecular pathogenesis of neurodegenerative disorders, such as Parkinson’s disease, Alzheimer’s disease, and other disorders. Common mechanisms of aging and neurodegeneration that are related to different mitophagy pathways provide a number of promising targets for potential therapeutic agents.

scholarly journals Brain Imaging Biomarkers for Chronic Pain

2022 ◽  
Vol 12 ◽  
Author(s):  
Zhengwu Zhang ◽  
Jennifer S. Gewandter ◽  
Paul Geha
Keyword(s):  
Chronic Pain ◽  
Brain Imaging ◽  
Substance Misuse ◽  
Clinical Applications ◽  
Imaging Biomarkers ◽  
Costs And Benefits ◽  
Brain Circuitry ◽  
Chronic Pain Conditions ◽  
The Brain

The prevalence of chronic pain has reached epidemic levels. In addition to personal suffering chronic pain is associated with psychiatric and medical co-morbidities, notably substance misuse, and a huge a societal cost amounting to hundreds of billions of dollars annually in medical cost, lost wages, and productivity. Chronic pain does not have a cure or quantitative diagnostic or prognostic tools. In this manuscript we provide evidence that this situation is about to change. We first start by summarizing our current understanding of the role of the brain in the pathogenesis of chronic pain. We particularly focus on the concept of learning in the emergence of chronic pain, and the implication of the limbic brain circuitry and dopaminergic signaling, which underly emotional learning and decision making, in this process. Next, we summarize data from our labs and from other groups on the latest brain imaging findings in different chronic pain conditions focusing on results with significant potential for translation into clinical applications. The gaps in the study of chronic pain and brain imaging are highlighted in throughout the overview. Finally, we conclude by discussing the costs and benefits of using brain biomarkers of chronic pain and compare to other potential markers.

scholarly journals Fluid Flow and Mass Transport in Brain Tissue

Fluids ◽  
2019 ◽  
Vol 4 (4) ◽  
pp. 196 ◽  
Author(s):  
Lori A. Ray ◽  
Jeffrey J. Heys
Keyword(s):  
Potential Role ◽  
Relevant Literature ◽  
Brain Dysfunction ◽  
Transport Processes ◽  
The Past ◽  
Advective Flows ◽  
The Brain ◽  
Flow And Mass Transport ◽  
Removal System

Despite its small size, the brain consumes 25% of the body’s energy, generating its own weight in potentially toxic proteins and biological debris each year. The brain is also the only organ lacking lymph vessels to assist in removal of interstitial waste. Over the past 50 years, a picture has been developing of the brain’s unique waste removal system. Experimental observations show cerebrospinal fluid, which surrounds the brain, enters the brain along discrete pathways, crosses a barrier into the spaces between brain cells, and flushes the tissue, carrying wastes to routes exiting the brain. Dysfunction of this cerebral waste clearance system has been demonstrated in Alzheimer’s disease, traumatic brain injury, diabetes, and stroke. The activity of the system is observed to increase during sleep. In addition to waste clearance, this circuit of flow may also deliver nutrients and neurotransmitters. Here, we review the relevant literature with a focus on transport processes, especially the potential role of diffusion and advective flows.

Is Neuraxial Clonidine a Safer Alternative to Opioids for Chronic Pain? An Alternative Worth Exploring

2020 ◽  
pp. 1-7
Author(s):  
Nagy Mekhail ◽  
Nagy Mekhail ◽  
Shrif Costandi ◽  
Alaa Abd-Elsayed ◽  
Gregory Fiore ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Pain Management ◽  
Potential Role ◽  
Common Side Effect ◽  
Chronic Pain Management ◽  
Inclusion Criteria ◽  
Opioid Use ◽  
Levels Of Evidence ◽  
The Past

Objective: Exploring the potential role of clonidine as an alternative to the currently available neuraxial medication options for the management of chronic pain. Methods: A comprehensive literature search was conducted investigating the treatment of chronic pain using clonidine over the past 73 years. A stepwise filtering approach was used to obtain articles addressing neuraxial treatment of chronic pain in adults. Selected articles were assessed for their levels of evidence followed by a discussion of their contribution to the understanding of the role of clonidine in chronic pain management. Results: Out of 1,035 articles that described the administration of clonidine for chronic pain management, seven articles met all of the inclusion criteria. Their levels of evidence ranged from 1a to 4 (Oxford Centre CEBM). Neuraxial administration of clonidine was found to be effective in the treatment of chronic pain, often exhibiting a synergistic effect with other analgesics to provide pain reduction with reduced opioid use. The most common side effect was hypotension, in some cases reported to have been serious. Conclusion: The use of neuraxial clonidine, in either a primary or adjunctive role, appears promising as an effective treatment for chronic pain.

scholarly journals MRI in the assessment and monitoring of multiple sclerosis: an update on best practice

2017 ◽  
Vol 10 (6) ◽  
pp. 247-261 ◽  
Author(s):  
Ulrike W. Kaunzner ◽  
Susan A. Gauthier
Keyword(s):  
Multiple Sclerosis ◽  
Best Practice ◽  
High Sensitivity ◽  
The Past ◽  
Assessment And Monitoring ◽  
Magnetic Resonance Imaging Mri ◽  
Improved Technology ◽  
Brain And Spinal Cord ◽  
The Brain

Magnetic resonance imaging (MRI) has developed into the most important tool for the diagnosis and monitoring of multiple sclerosis (MS). Its high sensitivity for the evaluation of inflammatory and neurodegenerative processes in the brain and spinal cord has made it the most commonly used technique for the evaluation of patients with MS. Moreover, MRI has become a powerful tool for treatment monitoring, safety assessment as well as for the prognostication of disease progression. Clinically, the use of MRI has increased in the past couple decades as a result of improved technology and increased availability that now extends well beyond academic centers. Consequently, there are numerous studies supporting the role of MRI in the management of patients with MS. The aim of this review is to summarize the latest insights into the utility of MRI in MS.

scholarly journals Central Nervous System Targets: Inhibitory Interneurons in the Spinal Cord

2020 ◽  
Vol 17 (3) ◽  
pp. 874-885 ◽  
Author(s):  
David I Hughes ◽  
Andrew J Todd
Keyword(s):  
Chronic Pain ◽  
Sensory Information ◽  
Protective Role ◽  
Inhibitory Interneurons ◽  
Pathological Conditions ◽  
Pain Pathways ◽  
Chronic Pain Patients ◽  
Cortical Regions ◽  
Pain Patients

Abstract Pain is a percept of critical importance to our daily survival. In most cases, it serves both an adaptive function by helping us respond appropriately in a potentially hostile environment and also a protective role by alerting us to tissue damage. Normally, it is evoked by the activation of peripheral nociceptive nerve endings and the subsequent relay of information to distinct cortical and sub-cortical regions, but under pathological conditions that result in chronic pain, it can become spontaneous. Given that one in three chronic pain patients do not respond to the treatments currently available, the need for more effective analgesics is evident. Two principal obstacles to the development of novel analgesic therapies are our limited understanding of how neuronal circuits that comprise these pain pathways transmit and modulate sensory information under normal circumstances and how these circuits change under pathological conditions leading to chronic pain states. In this review, we focus on the role of inhibitory interneurons in setting pain thresholds and, in particular, how disinhibition in the spinal dorsal horn can lead to aberrant sensory processing associated with chronic pain states.

scholarly journals Active Forgetting: Adaptation of Memory by Prefrontal Control

2021 ◽  
Vol 72 (1) ◽  
pp. 1-36 ◽  
Author(s):  
Michael C. Anderson ◽  
Justin C. Hulbert
Keyword(s):  
Emotional State ◽  
Memory Loss ◽  
Brain Structures ◽  
Past Century ◽  
Top Down ◽  
The Past ◽  
New Findings ◽  
Nonhuman Animals ◽  
The Brain

Over the past century, psychologists have discussed whether forgetting might arise from active mechanisms that promote memory loss to achieve various functions, such as minimizing errors, facilitating learning, or regulating one's emotional state. The past decade has witnessed a great expansion in knowledge about the brain mechanisms underlying active forgetting in its varying forms. A core discovery concerns the role of the prefrontal cortex in exerting top-down control over mnemonic activity in the hippocampus and other brain structures, often via inhibitory control. New findings reveal that such processes not only induce forgetting of specific memories but also can suppress the operation of mnemonic processes more broadly, triggering windows of anterograde and retrograde amnesia in healthy people. Recent work extends active forgetting to nonhuman animals, presaging the development of a multilevel mechanistic account that spans the cognitive, systems, network, and even cellular levels. This work reveals how organisms adapt their memories to their cognitive and emotional goals and has implications for understanding vulnerability to psychiatric disorders.

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