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Physiological Reviews Jan 2021Neuropathic pain caused by a lesion or disease of the somatosensory nervous system is a common chronic pain condition with major impact on quality of life. Examples... (Review)
Review
Neuropathic pain caused by a lesion or disease of the somatosensory nervous system is a common chronic pain condition with major impact on quality of life. Examples include trigeminal neuralgia, painful polyneuropathy, postherpetic neuralgia, and central poststroke pain. Most patients complain of an ongoing or intermittent spontaneous pain of, for example, burning, pricking, squeezing quality, which may be accompanied by evoked pain, particular to light touch and cold. Ectopic activity in, for example, nerve-end neuroma, compressed nerves or nerve roots, dorsal root ganglia, and the thalamus may in different conditions underlie the spontaneous pain. Evoked pain may spread to neighboring areas, and the underlying pathophysiology involves peripheral and central sensitization. Maladaptive structural changes and a number of cell-cell interactions and molecular signaling underlie the sensitization of nociceptive pathways. These include alteration in ion channels, activation of immune cells, glial-derived mediators, and epigenetic regulation. The major classes of therapeutics include drugs acting on αδ subunits of calcium channels, sodium channels, and descending modulatory inhibitory pathways.
Topics: Animals; Central Nervous System; Humans; Nerve Fibers; Neuralgia; Peripheral Nerves; Peripheral Nervous System
PubMed: 32584191
DOI: 10.1152/physrev.00045.2019 -
Cell Jan 2022Neurons of the mammalian central nervous system fail to regenerate. Substantial progress has been made toward identifying the cellular and molecular mechanisms that... (Review)
Review
Neurons of the mammalian central nervous system fail to regenerate. Substantial progress has been made toward identifying the cellular and molecular mechanisms that underlie regenerative failure and how altering those pathways can promote cell survival and/or axon regeneration. Here, we summarize those findings while comparing the regenerative process in the central versus the peripheral nervous system. We also highlight studies that advance our understanding of the mechanisms underlying neural degeneration in response to injury, as many of these mechanisms represent primary targets for restoring functional neural circuits.
Topics: Animals; Axons; Central Nervous System; Humans; Nerve Regeneration; Neurons; Peripheral Nervous System; Signal Transduction
PubMed: 34995518
DOI: 10.1016/j.cell.2021.10.029 -
Nature Reviews. Neuroscience Nov 2021The sympathetic nervous system prepares the body for 'fight or flight' responses and maintains homeostasis during daily activities such as exercise, eating a meal or... (Review)
Review
The sympathetic nervous system prepares the body for 'fight or flight' responses and maintains homeostasis during daily activities such as exercise, eating a meal or regulation of body temperature. Sympathetic regulation of bodily functions requires the establishment and refinement of anatomically and functionally precise connections between postganglionic sympathetic neurons and peripheral organs distributed widely throughout the body. Mechanistic studies of key events in the formation of postganglionic sympathetic neurons during embryonic and early postnatal life, including axon growth, target innervation, neuron survival, and dendrite growth and synapse formation, have advanced the understanding of how neuronal development is shaped by interactions with peripheral tissues and organs. Recent progress has also been made in identifying how the cellular and molecular diversity of sympathetic neurons is established to meet the functional demands of peripheral organs. In this Review, we summarize current knowledge of signalling pathways underlying the development of the sympathetic nervous system. These findings have implications for unravelling the contribution of sympathetic dysfunction stemming, in part, from developmental perturbations to the pathophysiology of peripheral neuropathies and cardiovascular and metabolic disorders.
Topics: Animals; Axons; Dendrites; Humans; Neuronal Plasticity; Neurons; Peripheral Nervous System Diseases; Sympathetic Nervous System
PubMed: 34599308
DOI: 10.1038/s41583-021-00523-y -
Development (Cambridge, England) May 2023The peripheral nervous system (PNS) represents a highly heterogeneous entity with a broad range of functions, ranging from providing communication between the brain and...
The peripheral nervous system (PNS) represents a highly heterogeneous entity with a broad range of functions, ranging from providing communication between the brain and the body to controlling development, stem cell niches and regenerative processes. According to the structure and function, the PNS can be subdivided into sensory, motor (i.e. the nerve fibers of motor neurons), autonomic and enteric domains. Different types of neurons correspond to these domains and recent progress in single-cell transcriptomics has enabled the discovery of new neuronal subtypes and improved the previous cell-type classifications. The developmental mechanisms generating the domains of the PNS reveal a range of embryonic strategies, including a variety of cell sources, such as migratory neural crest cells, placodal neurogenic cells and even recruited nerve-associated Schwann cell precursors. In this article, we discuss the diversity of roles played by the PNS in our body, as well as the origin, wiring and heterogeneity of every domain. We place a special focus on the most recent discoveries and concepts in PNS research, and provide an outlook of future perspectives and controversies in the field.
Topics: Peripheral Nervous System; Neurogenesis; Neural Crest; Schwann Cells; Motor Neurons
PubMed: 37170957
DOI: 10.1242/dev.201164 -
Current Pain and Headache Reports Jun 2017Our goal is to examine the processes-both central and peripheral-that underlie the development of peripherally-induced neuropathic pain (pNP) and to highlight recent... (Review)
Review
PURPOSE OF REVIEW
Our goal is to examine the processes-both central and peripheral-that underlie the development of peripherally-induced neuropathic pain (pNP) and to highlight recent evidence for mechanisms contributing to its maintenance. While many pNP conditions are initiated by damage to the peripheral nervous system (PNS), their persistence appears to rely on maladaptive processes within the central nervous system (CNS). The potential existence of an autonomous pain-generating mechanism in the CNS creates significant implications for the development of new neuropathic pain treatments; thus, work towards its resolution is crucial. Here, we seek to identify evidence for PNS and CNS independently generating neuropathic pain signals.
RECENT FINDINGS
Recent preclinical studies in pNP support and provide key details concerning the role of multiple mechanisms leading to fiber hyperexcitability and sustained electrical discharge to the CNS. In studies regarding central mechanisms, new preclinical evidence includes the mapping of novel inhibitory circuitry and identification of the molecular basis of microglia-neuron crosstalk. Recent clinical evidence demonstrates the essential role of peripheral mechanisms, mostly via studies that block the initially damaged peripheral circuitry. Clinical central mechanism studies use imaging to identify potentially self-sustaining infra-slow CNS oscillatory activity that may be unique to pNP patients. While new preclinical evidence supports and expands upon the key role of central mechanisms in neuropathic pain, clinical evidence for an autonomous central mechanism remains relatively limited. Recent findings from both preclinical and clinical studies recapitulate the critical contribution of peripheral input to maintenance of neuropathic pain. Further clinical investigations on the possibility of standalone central contributions to pNP may be assisted by a reconsideration of the agreed terms or criteria for diagnosing the presence of central sensitization in humans.
Topics: Central Nervous System; Humans; Neuralgia; Neurons; Peripheral Nervous System
PubMed: 28432601
DOI: 10.1007/s11916-017-0629-5 -
Biochimica Et Biophysica Acta. Reviews... Nov 2022Recent studies have shown that peripheral nerves play an important role in the progression of breast cancer. Breast cancer cells (BCCs) promote local peripheral nerve... (Review)
Review
Recent studies have shown that peripheral nerves play an important role in the progression of breast cancer. Breast cancer cells (BCCs) promote local peripheral nerve growth and branching by secreting neuroactive molecules, including neurotrophins and axon guidance molecules (AGMs). Sympathetic nerves promote breast cancer progression, while parasympathetic and sensory nerves mainly have anti-tumor effects in the progression of breast cancer. Specifically, peripheral nerves can influence the progression of breast cancer by secreting neurotransmitters not only directly binding to the corresponding receptors of BCCs, but also indirectly acting on immune cells to modulate anti-tumor immunity. In this review, we summarize the crosstalk between breast cancer and peripheral nerves and the roles of important neuroactive molecules in the progression of breast cancer. In addition, we summarize indicators, including nerve fiber density and perineural invasion (PNI), that may help determine the prognosis of breast cancer based on current research results, as well as potential therapeutic approaches, such as β-blockers and retroviral-mediated genetic neuroengineering techniques, that may enhance the prognosis of breast cancer. In addition, we propose suggestions for future research priorities based on a current lack of knowledge in this area.
Topics: Humans; Female; Neoplasm Invasiveness; Breast Neoplasms; Axon Guidance; Peripheral Nervous System
PubMed: 36283598
DOI: 10.1016/j.bbcan.2022.188828 -
Neuron May 2018Itch is a unique sensory experience that is encoded by genetically distinguishable neurons both in the peripheral nervous system (PNS) and central nervous system (CNS)... (Review)
Review
Itch is a unique sensory experience that is encoded by genetically distinguishable neurons both in the peripheral nervous system (PNS) and central nervous system (CNS) to elicit a characteristic behavioral response (scratching). Itch interacts with the other sensory modalities at multiple locations, from its initiation in a particular dermatome to its transmission to the brain where it is finally perceived. In this review, we summarize the current understanding of the molecular and neural mechanisms of itch by starting in the periphery, where itch is initiated, and discussing the circuits involved in itch processing in the CNS.
Topics: Animals; Central Nervous System; Humans; Peripheral Nervous System; Pruritus; Receptors, G-Protein-Coupled; Sensory Receptor Cells; Skin; Spinal Cord
PubMed: 29723501
DOI: 10.1016/j.neuron.2018.03.023 -
Annual Review of Cell and Developmental... Oct 2019Molecular cross talk between the nervous and vascular systems is necessary to maintain the correct coupling of organ structure and function. Molecular pathways shared by... (Review)
Review
Molecular cross talk between the nervous and vascular systems is necessary to maintain the correct coupling of organ structure and function. Molecular pathways shared by both systems are emerging as major players in the communication of the neuronal compartment with the endothelium. Here we review different aspects of this cross talk and how vessels influence the development and homeostasis of the nervous system. Beyond the classical role of the vasculature as a conduit to deliver oxygen and metabolites needed for the energy-demanding neuronal compartment, vessels emerge as powerful signaling systems that control and instruct a variety of cellular processes during the development of neurons and glia, such as migration, differentiation, and structural connectivity. Moreover, a broad spectrum of mild to severe vascular dysfunctions occur in various pathologies of the nervous system, suggesting that mild structural and functional changes at the neurovascular interface may underlie cognitive decline in many of these pathological conditions.
Topics: Animals; Blood Vessels; Cell Differentiation; Cell Movement; Central Nervous System; Homeostasis; Humans; Nervous System Diseases; Neuroglia; Neurons; Neurovascular Coupling; Peripheral Nervous System
PubMed: 31590587
DOI: 10.1146/annurev-cellbio-100818-125142 -
Annual Review of Neuroscience Jul 2019Maturation of neuronal circuits requires selective elimination of synaptic connections. Although neuron-intrinsic mechanisms are important in this process, it is... (Review)
Review
Maturation of neuronal circuits requires selective elimination of synaptic connections. Although neuron-intrinsic mechanisms are important in this process, it is increasingly recognized that glial cells also play a critical role. Without proper functioning of these cells, the number, morphology, and function of synaptic contacts are profoundly altered, resulting in abnormal connectivity and behavioral abnormalities. In addition to their role in synaptic refinement, glial cells have also been implicated in pathological synapse loss and dysfunction following injury or nervous system degeneration in adults. Although mechanisms regulating glia-mediated synaptic elimination are still being uncovered, it is clear this complex process involves many cues that promote and inhibit the removal of specific synaptic connections. Gaining a greater understanding of these signals and the contribution of different cell types will not only provide insight into this critical biological event but also be instrumental in advancing knowledge of brain development and neural disease.
Topics: Animals; Astrocytes; Biological Evolution; Central Nervous System; Cues; Exosomes; Humans; Invertebrates; Microglia; Morphogenesis; Myelin Sheath; Nerve Degeneration; Nervous System Diseases; Neuroglia; Neuromuscular Junction; Neurons; Peripheral Nervous System; Synapses
PubMed: 31283900
DOI: 10.1146/annurev-neuro-070918-050306 -
Trends in Immunology Dec 2018Relentless, repetitive itching and scratching is a debilitating feature of many chronic inflammatory skin disorders such as atopic dermatitis. While well known... (Review)
Review
Relentless, repetitive itching and scratching is a debilitating feature of many chronic inflammatory skin disorders such as atopic dermatitis. While well known clinically, this itch-scratch cycle has historically lacked in-depth mechanistic understanding. However, recent advances at the interface of itch neurobiology and skin immunology have shed new light on this phenomenon. In this review, we highlight recent advances in our understanding of the neuroimmunology of chronic itch centered around three key points of entry into the itch-scratch cycle: the epithelial barrier, the immune system, and the peripheral nervous system. Furthermore, we explore novel neuro-epithelial-immune interactions that may represent promising therapeutic paradigms.
Topics: Animals; Humans; Peripheral Nervous System; Pruritus
PubMed: 30471983
DOI: 10.1016/j.it.2018.10.001