Review

Authors: Nanna Brix Finnerup, Rohini Kuner, Troels Staehelin Jensen...

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

Review

Authors: Stephen W Porges

The polyvagal theory introduced a new perspective relating autonomic function to behavior, that included an appreciation of the autonomic nervous system as a "system," the identification of neural circuits involved in the regulation of autonomic state, and an interpretation of autonomic reactivity as adaptive within the context of the phylogeny of the vertebrate autonomic nervous system. The paper has two objectives: first, to provide an explicit statement of the theory; and second, to introduce the features of a polyvagal perspective. The polyvagal perspective emphasizes how an understanding of neurophysiological mechanisms and phylogenetic shifts in neural regulation leads to different questions, paradigms, explanations, and conclusions regarding autonomic function in biobehavioral processes than peripheral models. Foremost, the polyvagal perspective emphasizes the importance of phylogenetic changes in the neural structures regulating the autonomic nervous system and how these phylogenetic shifts provide insights into the adaptive function and the neural regulation of the two vagal systems.

Topics: Adaptation, Physiological; Arrhythmia, Sinus; Autonomic Nervous System; Brain Stem; Cerebral Cortex; Environment; Heart Rate; Humans; Limbic System; Nerve Net; Parasympathetic Nervous System; Peripheral Nervous System; Phylogeny; Pressoreceptors; Psychomotor Performance; Vagus Nerve

PubMed: 17049418
DOI: 10.1016/j.biopsycho.2006.06.009

Review

Authors: Xintong Dong, Xinzhong Dong

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

Review

Authors: Mar Bosch-Queralt, Robert Fledrich, Ruth M Stassart...

The glial cell of the peripheral nervous system (PNS), the Schwann cell (SC), counts among the most multifaceted cells of the body. During development, SCs secure neuronal survival and participate in axonal path finding. Simultaneously, they orchestrate the architectural set up of the developing nerves, including the blood vessels and the endo-, peri- and epineurial layers. Perinatally, in rodents, SCs radially sort and subsequently myelinate individual axons larger than 1 μm in diameter, while small calibre axons become organised in non-myelinating Remak bundles. SCs have a vital role in maintaining axonal health throughout life and several specialized SC types perform essential functions at specific locations, such as terminal SC at the neuromuscular junction (NMJ) or SC within cutaneous sensory end organs. In addition, neural crest derived satellite glia maintain a tight communication with the soma of sensory, sympathetic, and parasympathetic neurons and neural crest derivatives are furthermore an indispensable part of the enteric nervous system. The remarkable plasticity of SCs becomes evident in the context of a nerve injury, where SC transdifferentiate into intriguing repair cells, which orchestrate a regenerative response that promotes nerve repair. Indeed, the multiple adaptations of SCs are captivating, but remain often ill-resolved on the molecular level. Here, we summarize and discuss the knowns and unknowns of the vast array of functions that this single cell type can cover in peripheral nervous system development, maintenance, and repair.

Topics: Humans; Schwann Cells; Peripheral Nerves; Axons; Neurons; Peripheral Nervous System; Nerve Regeneration; Peripheral Nerve Injuries

PubMed: 36493976
DOI: 10.1016/j.nbd.2022.105952

Review

Authors: William C de Groat, Derek Griffiths, Naoki Yoshimura...

This article summarizes anatomical, neurophysiological, pharmacological, and brain imaging studies in humans and animals that have provided insights into the neural circuitry and neurotransmitter mechanisms controlling the lower urinary tract. The functions of the lower urinary tract to store and periodically eliminate urine are regulated by a complex neural control system in the brain, spinal cord, and peripheral autonomic ganglia that coordinates the activity of smooth and striated muscles of the bladder and urethral outlet. The neural control of micturition is organized as a hierarchical system in which spinal storage mechanisms are in turn regulated by circuitry in the rostral brain stem that initiates reflex voiding. Input from the forebrain triggers voluntary voiding by modulating the brain stem circuitry. Many neural circuits controlling the lower urinary tract exhibit switch-like patterns of activity that turn on and off in an all-or-none manner. The major component of the micturition switching circuit is a spinobulbospinal parasympathetic reflex pathway that has essential connections in the periaqueductal gray and pontine micturition center. A computer model of this circuit that mimics the switching functions of the bladder and urethra at the onset of micturition is described. Micturition occurs involuntarily in infants and young children until the age of 3 to 5 years, after which it is regulated voluntarily. Diseases or injuries of the nervous system in adults can cause the re-emergence of involuntary micturition, leading to urinary incontinence. Neuroplasticity underlying these developmental and pathological changes in voiding function is discussed.

Topics: Animals; Humans; Neuronal Plasticity; Neurons, Afferent; Neurotransmitter Agents; Peripheral Nervous System; Reflex; Spinal Cord; Urethra; Urinary Bladder; Urinary Tract; Urination

PubMed: 25589273
DOI: 10.1002/cphy.c130056

Review

Authors: Madison R Mack, Brian S Kim

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

Review

Authors: Michael Costigan, Joachim Scholz, Clifford J Woolf...

Neuropathic pain is triggered by lesions to the somatosensory nervous system that alter its structure and function so that pain occurs spontaneously and responses to noxious and innocuous stimuli are pathologically amplified. The pain is an expression of maladaptive plasticity within the nociceptive system, a series of changes that constitute a neural disease state. Multiple alterations distributed widely across the nervous system contribute to complex pain phenotypes. These alterations include ectopic generation of action potentials, facilitation and disinhibition of synaptic transmission, loss of synaptic connectivity and formation of new synaptic circuits, and neuroimmune interactions. Although neural lesions are necessary, they are not sufficient to generate neuropathic pain; genetic polymorphisms, gender, and age all influence the risk of developing persistent pain. Treatment needs to move from merely suppressing symptoms to a disease-modifying strategy aimed at both preventing maladaptive plasticity and reducing intrinsic risk.

Topics: Adaptation, Physiological; Afferent Pathways; Animals; Humans; Nervous System; Neuralgia; Neuronal Plasticity; Nociceptors; Pain Threshold; Peripheral Nervous System Diseases; Sensory Receptor Cells; Signal Transduction; Spinal Nerve Roots

PubMed: 19400724
DOI: 10.1146/annurev.neuro.051508.135531

Review

Authors: Alessandra Bortoluzzi, Ettore Silvagni, Federica Furini...

In the past years the peripheral nervous system (PNS) involvement in systemic lupus erythematosus (SLE) has received little attention despite its potential significant impact. The true prevalence of PNS in SLE reported in studies is variable and strongly influenced by American College of Rheumatology (ACR) case definition that includes seven PNS manifestations (acute inflammatory demyelinating polyradiculoneuropathy, autonomic disorder, mononeuropathy, myasthenia gravis, cranial neuropathy, plexopathy and polyneuropathy). Other peripheral manifestations, such as chronic inflammatory demyelinating polyradiculoneuropathy and small fibre neuropathy, not included in the ACR nomenclature, have not been well characterised in SLE. The aim of this review is to focus on epidemiology, pathogenesis, diagnosis and clinical features of all possible different expressions of PNS involvement in SLE, with the final objective to profile the patient's clinical characteristics.

Topics: Humans; Lupus Erythematosus, Systemic; Peripheral Nervous System; Peripheral Nervous System Diseases

PubMed: 29846158
DOI: No ID Found

Review

Authors: Eva L Feldman, Klaus-Armin Nave, Troels S Jensen...

Pre-diabetes and diabetes are a global epidemic, and the associated neuropathic complications create a substantial burden on both the afflicted patients and society as a whole. Given the enormity of the problem and the lack of effective therapies, there is a pressing need to understand the mechanisms underlying diabetic neuropathy (DN). In this review, we present the structural components of the peripheral nervous system that underlie its susceptibility to metabolic insults and then discuss the pathways that contribute to peripheral nerve injury in DN. We also discuss systems biology insights gleaned from the recent advances in biotechnology and bioinformatics, emerging ideas centered on the axon-Schwann cell relationship and associated bioenergetic crosstalk, and the rapid expansion of our knowledge of the mechanisms contributing to neuropathic pain in diabetes. These recent advances in our understanding of DN pathogenesis are paving the way for critical mechanism-based therapy development.

Topics: Animals; Axons; Diabetic Neuropathies; Energy Metabolism; Humans; Models, Neurological; Neuralgia; Peripheral Nervous System; Schwann Cells

PubMed: 28334605
DOI: 10.1016/j.neuron.2017.02.005

Authors: Jan Korabecny, Ondrej Soukup

Cholinesterases are fundamental players in the peripheral and central nervous systems [...].

Topics: Acetylcholinesterase; Animals; Butyrylcholinesterase; Central Nervous System; Cholinesterase Inhibitors; GPI-Linked Proteins; Gene Expression; Humans; Neurodegenerative Diseases; Neurons; Neuroprotective Agents; Peripheral Nervous System; Synapses; Synaptic Transmission

PubMed: 34439787
DOI: 10.3390/biom11081121