Abstract Brain circuits involved in pain chronicity shift from areas involved in nociceptive processing to those associated with emotional and motivational processes. They overlap with circuits relevant for anxiety, fear and depression and are characterized by deficient prefrontal control mechanisms. Noninvasive brain stimulation techniques such as repetitive transcranial magnetic stimulation, transcranial direct and alternating current stimulation directly impact on these circuits and pain. Neurofeedback and brain-computer interfaces as well as various types of cognitive and behavioral interventions also alter these circuits. The analysis of brain changes related to pain chronicity helps to mechanistically tailor interventions to patient characteristics, can increase treatment efficacy and efficiency and can identify new treatment approaches.
{"title":"Brain-based interventions for chronic pain","authors":"Herta Flor, R. Kuner","doi":"10.1515/nf-2021-0037","DOIUrl":"https://doi.org/10.1515/nf-2021-0037","url":null,"abstract":"Abstract Brain circuits involved in pain chronicity shift from areas involved in nociceptive processing to those associated with emotional and motivational processes. They overlap with circuits relevant for anxiety, fear and depression and are characterized by deficient prefrontal control mechanisms. Noninvasive brain stimulation techniques such as repetitive transcranial magnetic stimulation, transcranial direct and alternating current stimulation directly impact on these circuits and pain. Neurofeedback and brain-computer interfaces as well as various types of cognitive and behavioral interventions also alter these circuits. The analysis of brain changes related to pain chronicity helps to mechanistically tailor interventions to patient characteristics, can increase treatment efficacy and efficiency and can identify new treatment approaches.","PeriodicalId":56108,"journal":{"name":"Neuroforum","volume":"28 1","pages":"95 - 104"},"PeriodicalIF":0.0,"publicationDate":"2022-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45740148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract According to best current estimates, approximately 10% of those infected with SARS-CoV-2-virus experience long-term clinical and nonspecific neurological symptoms that may last for several weeks or months. This is currently referred to as “Long-COVID” or “Post-COVID-Syndrome”. Based on current knowledge, the most common long-term symptoms of COVID-19 disease include fatigue and poor concentration, but particularly also headache and musculoskeletal pain. However, given the novelty of COVID-19, only a few studies have systematically evaluated the central nervous alterations in the pain processing structures of our brain. Those first insights are yet important in order to offer patients adequate therapeutic options. Based on a systematic review of the literature, we will therefore provide an overview of the central nervous alterations in the brain described in the context of SARS-CoV-2 infection, focusing on findings with brain imaging.
{"title":"Pain, the brain, and SARS-CoV-2: evidence for pain-specific alterations in brain-related structure–function properties","authors":"J. Tesarz, F. Nees","doi":"10.1515/nf-2021-0034","DOIUrl":"https://doi.org/10.1515/nf-2021-0034","url":null,"abstract":"Abstract According to best current estimates, approximately 10% of those infected with SARS-CoV-2-virus experience long-term clinical and nonspecific neurological symptoms that may last for several weeks or months. This is currently referred to as “Long-COVID” or “Post-COVID-Syndrome”. Based on current knowledge, the most common long-term symptoms of COVID-19 disease include fatigue and poor concentration, but particularly also headache and musculoskeletal pain. However, given the novelty of COVID-19, only a few studies have systematically evaluated the central nervous alterations in the pain processing structures of our brain. Those first insights are yet important in order to offer patients adequate therapeutic options. Based on a systematic review of the literature, we will therefore provide an overview of the central nervous alterations in the brain described in the context of SARS-CoV-2 infection, focusing on findings with brain imaging.","PeriodicalId":56108,"journal":{"name":"Neuroforum","volume":"28 1","pages":"105 - 116"},"PeriodicalIF":0.0,"publicationDate":"2022-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47023649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Voltage-gated sodium channels are crucial for pain perception. This is illustrated by several human genetic conditions that lead to either chronic pain or, vice versa, to congenital painlessness. The type of mutation, its impact on neuron excitability as well as the affected sodium channel subtype delineates a complex picture of the disorders. Genetic variants in sodium channels may affect the complex biophysical gating and also their trafficking, association with other proteins and more complex regulations of the channel protein and function, thus allowing us to explore the subtle but impactful effects of their dysregulation for human nociception. A detailed understanding of these pain disorders provides a unique chance to understand the detailed intricacies of nociception and pathological conditions such as neuropathic pain. With increasing awareness of the importance of sodium channel variants in neuropathic pain, more patients are genetically screened, sometimes identifying variants of unclear significance (VUS). Bioinformatic tools help to assess their potential disease causing impact, but functional studies using patch-clamp experiments in cell lines are needed to allow for reliable conclusions. Often cell lines are not sufficient to show a physiologically relevant phenotype and more complex, time intensive models, such as induced pluripotent stem cells (iPS-cells) are employed. A challenge remains to identify the role of each sodium channel VUS in the context of the detailed cellular genetic and functional context. To lay the grounds for such a detailed interpretation, we need a correlation of cellular function and genetic transcription on a single cell basis, as it is possible with the Patch-Seq technique. The more detailed our knowledge becomes on functional and genetic sensory neurons subtypes and their role in the generation of neuropathic pain, the more targeted the personal or population-based treatment can be.
{"title":"Genetics meets function in sodium channel-related pain disorders","authors":"Jannis Körner, N. Haag, I. Kurth, A. Lampert","doi":"10.1515/nf-2021-0035","DOIUrl":"https://doi.org/10.1515/nf-2021-0035","url":null,"abstract":"Abstract Voltage-gated sodium channels are crucial for pain perception. This is illustrated by several human genetic conditions that lead to either chronic pain or, vice versa, to congenital painlessness. The type of mutation, its impact on neuron excitability as well as the affected sodium channel subtype delineates a complex picture of the disorders. Genetic variants in sodium channels may affect the complex biophysical gating and also their trafficking, association with other proteins and more complex regulations of the channel protein and function, thus allowing us to explore the subtle but impactful effects of their dysregulation for human nociception. A detailed understanding of these pain disorders provides a unique chance to understand the detailed intricacies of nociception and pathological conditions such as neuropathic pain. With increasing awareness of the importance of sodium channel variants in neuropathic pain, more patients are genetically screened, sometimes identifying variants of unclear significance (VUS). Bioinformatic tools help to assess their potential disease causing impact, but functional studies using patch-clamp experiments in cell lines are needed to allow for reliable conclusions. Often cell lines are not sufficient to show a physiologically relevant phenotype and more complex, time intensive models, such as induced pluripotent stem cells (iPS-cells) are employed. A challenge remains to identify the role of each sodium channel VUS in the context of the detailed cellular genetic and functional context. To lay the grounds for such a detailed interpretation, we need a correlation of cellular function and genetic transcription on a single cell basis, as it is possible with the Patch-Seq technique. The more detailed our knowledge becomes on functional and genetic sensory neurons subtypes and their role in the generation of neuropathic pain, the more targeted the personal or population-based treatment can be.","PeriodicalId":56108,"journal":{"name":"Neuroforum","volume":"28 1","pages":"67 - 75"},"PeriodicalIF":0.0,"publicationDate":"2022-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45984070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elisa Damo, Phillip Rieder, Ilknur Coban, Rangel Leal Silva, Frank Kirchhoff, Manuela Simonetti, Amit Agarwal
Abstract Several forms of chronic pain do not respond to the conventional analgesics, such as opioids, but can be treated with antidepressants, such as serotonin and noradrenalin reuptake inhibitors (SNRIs). Recent studies indicate that noradrenalin signalling is a key target for SNRI-induced analgesia in neuropathic pain. SNRIs inhibit chronic pain by blocking reuptake of noradrenalin and subsequent activation of adrenergic receptors on neurons in the dorsal horn of the spinal cord. However, in the nervous system, various subtypes of adrenergic receptors are highly expressed by astrocytes and microglial cells. Activation of these receptors on astrocytes engages complex intracellular signalling pathways and prevents inflammatory changes of microglia, which in turn can affect neuronal activity. Hence, SNRIs-induced modulations of the glial cell physiology can impact neural circuit functions and pain perception. In this review, we summarize our current knowledge on the impact of SNRIs on glial cells and in modulating chronic pain in experimental animal models.
{"title":"Glial cells as target for antidepressants in neuropathic pain","authors":"Elisa Damo, Phillip Rieder, Ilknur Coban, Rangel Leal Silva, Frank Kirchhoff, Manuela Simonetti, Amit Agarwal","doi":"10.1515/nf-2021-0036","DOIUrl":"https://doi.org/10.1515/nf-2021-0036","url":null,"abstract":"Abstract Several forms of chronic pain do not respond to the conventional analgesics, such as opioids, but can be treated with antidepressants, such as serotonin and noradrenalin reuptake inhibitors (SNRIs). Recent studies indicate that noradrenalin signalling is a key target for SNRI-induced analgesia in neuropathic pain. SNRIs inhibit chronic pain by blocking reuptake of noradrenalin and subsequent activation of adrenergic receptors on neurons in the dorsal horn of the spinal cord. However, in the nervous system, various subtypes of adrenergic receptors are highly expressed by astrocytes and microglial cells. Activation of these receptors on astrocytes engages complex intracellular signalling pathways and prevents inflammatory changes of microglia, which in turn can affect neuronal activity. Hence, SNRIs-induced modulations of the glial cell physiology can impact neural circuit functions and pain perception. In this review, we summarize our current knowledge on the impact of SNRIs on glial cells and in modulating chronic pain in experimental animal models.","PeriodicalId":56108,"journal":{"name":"Neuroforum","volume":"28 1","pages":"85 - 94"},"PeriodicalIF":0.0,"publicationDate":"2022-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45078669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H. Schaible, A. Ebersberger, G. Natura, E. Vazquez
Abstract Interactions of the immune system and the nociceptive system play an important role in the generation and maintenance of pain in musculoskeletal diseases and in disease development. In inflamed tissue peripheral nociceptive neurons are rendered hyperexcitable by proinflammatory cytokines, antigen/antibody complexes and other immune mediators. Spinal nociceptive neurons are rendered hyperexcitable with the support of microglial cells, the immune cells of the central nervous system. The so-elicited sensitization of pain pathways has a strong impact on pain processing in the brain. On the other hand, immune processes are regulated by the nervous system. Sensory neurons, by releasing neuropeptides, and efferent neurons of the sympathetic nervous system support immune processes which promote disease development.
{"title":"The role of neuroimmune interactions in musculoskeletal pain","authors":"H. Schaible, A. Ebersberger, G. Natura, E. Vazquez","doi":"10.1515/nf-2022-0001","DOIUrl":"https://doi.org/10.1515/nf-2022-0001","url":null,"abstract":"Abstract Interactions of the immune system and the nociceptive system play an important role in the generation and maintenance of pain in musculoskeletal diseases and in disease development. In inflamed tissue peripheral nociceptive neurons are rendered hyperexcitable by proinflammatory cytokines, antigen/antibody complexes and other immune mediators. Spinal nociceptive neurons are rendered hyperexcitable with the support of microglial cells, the immune cells of the central nervous system. The so-elicited sensitization of pain pathways has a strong impact on pain processing in the brain. On the other hand, immune processes are regulated by the nervous system. Sensory neurons, by releasing neuropeptides, and efferent neurons of the sympathetic nervous system support immune processes which promote disease development.","PeriodicalId":56108,"journal":{"name":"Neuroforum","volume":"28 1","pages":"77 - 84"},"PeriodicalIF":0.0,"publicationDate":"2022-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45166689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-02-23Epub Date: 2021-12-31DOI: 10.1515/nf-2021-0031
Jan H Kirchner, Julijana Gjorgjieva
Single neurons in the brain exhibit astounding computational capabilities, which gradually emerge throughout development and enable them to become integrated into complex neural circuits. These capabilities derive in part from the precise arrangement of synaptic inputs on the neurons' dendrites. While the full computational benefits of this arrangement are still unknown, a picture emerges in which synapses organize according to their functional properties across multiple spatial scales. In particular, on the local scale (tens of microns), excitatory synaptic inputs tend to form clusters according to their functional similarity, whereas on the scale of individual dendrites or the entire tree, synaptic inputs exhibit dendritic maps where excitatory synapse function varies smoothly with location on the tree. The development of this organization is supported by inhibitory synapses, which are carefully interleaved with excitatory synapses and can flexibly modulate activity and plasticity of excitatory synapses. Here, we summarize recent experimental and theoretical research on the developmental emergence of this synaptic organization and its impact on neural computations.
{"title":"Emergence of synaptic organization and computation in dendrites.","authors":"Jan H Kirchner, Julijana Gjorgjieva","doi":"10.1515/nf-2021-0031","DOIUrl":"10.1515/nf-2021-0031","url":null,"abstract":"<p><p>Single neurons in the brain exhibit astounding computational capabilities, which gradually emerge throughout development and enable them to become integrated into complex neural circuits. These capabilities derive in part from the precise arrangement of synaptic inputs on the neurons' dendrites. While the full computational benefits of this arrangement are still unknown, a picture emerges in which synapses organize according to their functional properties across multiple spatial scales. In particular, on the local scale (tens of microns), excitatory synaptic inputs tend to form clusters according to their functional similarity, whereas on the scale of individual dendrites or the entire tree, synaptic inputs exhibit dendritic maps where excitatory synapse function varies smoothly with location on the tree. The development of this organization is supported by inhibitory synapses, which are carefully interleaved with excitatory synapses and can flexibly modulate activity and plasticity of excitatory synapses. Here, we summarize recent experimental and theoretical research on the developmental emergence of this synaptic organization and its impact on neural computations.</p>","PeriodicalId":56108,"journal":{"name":"Neuroforum","volume":"28 1","pages":"21-30"},"PeriodicalIF":0.0,"publicationDate":"2022-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8887907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40538691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Brain development comprises a fine-tuned ensemble of molecular processes that need to be orchestrated in a very coordinated way throughout time and space. A wide array of epigenetic mechanisms, ranging from DNA methylation and histone modifications to noncoding RNAs, have been identified for their major role in guiding developmental processes such as progenitor proliferation, neuronal migration, and differentiation through precise regulation of gene expression programs. The importance of epigenetic processes during development is reflected by the high prevalence of neurodevelopmental diseases which are caused by a lack or mutation of genes encoding for transcription factors and other epigenetic regulators. Most of these factors process central functions for proper brain development, and respective mutations lead to severe cognitive defects. A better understanding of epigenetic programs during development might open new routes toward better treatment options for related diseases.
{"title":"Epigenetic function in neurodevelopment and cognitive impairment","authors":"Mira Jakovcevski, Geraldine Zimmer-Bensch","doi":"10.1515/nf-2021-0028","DOIUrl":"https://doi.org/10.1515/nf-2021-0028","url":null,"abstract":"Abstract Brain development comprises a fine-tuned ensemble of molecular processes that need to be orchestrated in a very coordinated way throughout time and space. A wide array of epigenetic mechanisms, ranging from DNA methylation and histone modifications to noncoding RNAs, have been identified for their major role in guiding developmental processes such as progenitor proliferation, neuronal migration, and differentiation through precise regulation of gene expression programs. The importance of epigenetic processes during development is reflected by the high prevalence of neurodevelopmental diseases which are caused by a lack or mutation of genes encoding for transcription factors and other epigenetic regulators. Most of these factors process central functions for proper brain development, and respective mutations lead to severe cognitive defects. A better understanding of epigenetic programs during development might open new routes toward better treatment options for related diseases.","PeriodicalId":56108,"journal":{"name":"Neuroforum","volume":"28 1","pages":"41 - 53"},"PeriodicalIF":0.0,"publicationDate":"2021-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47304982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract To provide a compact and efficient input to the brain, sensory systems separate the incoming information into parallel feature channels. In the visual system, parallel processing starts in the retina. Here, the image is decomposed into multiple retinal output channels, each selective for a specific set of visual features like motion, contrast, or edges. In this article, we will summarize recent findings on the functional organization of the retinal output, the neural mechanisms underlying its diversity, and how single visual features, like color, are extracted by the retinal network. Unraveling how the retina – as the first stage of the visual system – filters the visual input is an important step toward understanding how visual information processing guides behavior.
{"title":"What the eye tells the brain: retinal feature extraction","authors":"Klaudia P. Szatko, K. Franke","doi":"10.1515/nf-2021-0032","DOIUrl":"https://doi.org/10.1515/nf-2021-0032","url":null,"abstract":"Abstract To provide a compact and efficient input to the brain, sensory systems separate the incoming information into parallel feature channels. In the visual system, parallel processing starts in the retina. Here, the image is decomposed into multiple retinal output channels, each selective for a specific set of visual features like motion, contrast, or edges. In this article, we will summarize recent findings on the functional organization of the retinal output, the neural mechanisms underlying its diversity, and how single visual features, like color, are extracted by the retinal network. Unraveling how the retina – as the first stage of the visual system – filters the visual input is an important step toward understanding how visual information processing guides behavior.","PeriodicalId":56108,"journal":{"name":"Neuroforum","volume":"28 1","pages":"13 - 19"},"PeriodicalIF":0.0,"publicationDate":"2021-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67144939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Stroke is a leading cause of death and disability worldwide with limited therapeutic options available for selected groups of patients. The susceptibility to stroke depends also on systemic parameters, and some stroke risk factors are modifiable, such as atrial fibrillation (AF) or hypertension. When considering new treatment strategies, it is important to remember that the consequences of stroke are not limited to the central nervous system (CNS) injury, but reach beyond the boundaries of the brain. We provide here a brief overview of the mechanisms of how the brain communicates with the body, focusing on the heart, immune system, and gut microbiota (GM).
{"title":"Brain–body communication in stroke","authors":"K. Winek, Daniel Cuervo Zanatta, M. Zille","doi":"10.1515/nf-2021-0030","DOIUrl":"https://doi.org/10.1515/nf-2021-0030","url":null,"abstract":"Abstract Stroke is a leading cause of death and disability worldwide with limited therapeutic options available for selected groups of patients. The susceptibility to stroke depends also on systemic parameters, and some stroke risk factors are modifiable, such as atrial fibrillation (AF) or hypertension. When considering new treatment strategies, it is important to remember that the consequences of stroke are not limited to the central nervous system (CNS) injury, but reach beyond the boundaries of the brain. We provide here a brief overview of the mechanisms of how the brain communicates with the body, focusing on the heart, immune system, and gut microbiota (GM).","PeriodicalId":56108,"journal":{"name":"Neuroforum","volume":"28 1","pages":"31 - 39"},"PeriodicalIF":0.0,"publicationDate":"2021-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45151009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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