Neural Circuits of Interoception

Trends in Neurosciences, Journal Year: 2020, Volume and Issue: 44(1), P. 17 - 28

Published: Dec. 29, 2020

Language: Английский

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The mechanosensory neurons of touch and their mechanisms of activation

Nature reviews. Neuroscience, Journal Year: 2021, Volume and Issue: 22(9), P. 521 - 537

Published: July 26, 2021

Language: Английский

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Regulation of pain by neuro-immune interactions between macrophages and nociceptor sensory neurons

Current Opinion in Neurobiology, Journal Year: 2019, Volume and Issue: 62, P. 17 - 25

Published: Dec. 3, 2019

Language: Английский

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Physiology and Pathophysiology of Itch

Physiological Reviews, Journal Year: 2019, Volume and Issue: 100(3), P. 945 - 982

Published: Dec. 23, 2019

Itch is a topic to which everyone can relate. The physiological roles of itch are increasingly understood and appreciated. pathophysiological consequences impact quality life as much pain. These dynamics have led deep dives into the mechanisms that underlie contribute sensation itch. When prior review on physiology itching was published in this journal 1941, black box interest small number neuroscientists dermatologists. now appreciated complex colorful Rubik’s cube. Acute chronic being carefully scratched apart reassembled by puzzle solvers across biomedical spectrum. New mediators identified. Mechanisms blur boundaries circuitry blend neuroscience immunology. Measures involve psychophysics behavioral psychology. efforts associated with these approaches positively impacting care itchy patients. There potential markedly alleviate itch, condition does not end life, but often ruins it. We field provide current understanding pathophysiology disease, only symptom disease.

Language: Английский

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Painful and non-painful diabetic neuropathy, diagnostic challenges and implications for future management

Brain, Journal Year: 2021, Volume and Issue: 144(6), P. 1632 - 1645

Published: March 9, 2021

Peripheral neuropathy is one of the most common complications both type 1 and 2 diabetes. Up to half patients with diabetes develop during course their disease, which accompanied by neuropathic pain in 30-40% cases. nerve injury can manifest as progressive distal symmetric polyneuropathy, autonomic neuropathy, radiculo-plexopathies, mononeuropathies. The diabetic we will refer DN, its characteristic glove stocking like presentation sensory or motor function loss. DN painful counterpart, are associated increased mortality morbidity; thus, early recognition preventive measures essential. Nevertheless, it not easy diagnose particularly mild there currently no single established diagnostic gold standard. approach research a hierarchical system, combines symptoms, signs, series confirmatory tests. general lack long-term prospective studies has limited evaluation sensitivity specificity new morphometric neurophysiological techniques. Thus, best paradigm for screening clinical practice remains uncertain. Herein, review challenges from perspectives implications managing DN. There treatment, apart improved glycaemic control, more effective than diabetes, only symptomatic management available Currently, less one-third derive sufficient relief existing pharmacotherapies. A precise distinct profile may help identify responsive treatment versus another. Detailed profiles lead tailored patient subgroups matching novel pathomechanisms also trials stratification. Large randomized needed interventions, i.e. pharmacological, physical, cognitive, educational, etc., therapeutic outcomes.

Language: Английский

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Studying human nociceptors: from fundamentals to clinic

Brain, Journal Year: 2021, Volume and Issue: 144(5), P. 1312 - 1335

Published: Feb. 10, 2021

Abstract Chronic pain affects one in five of the general population and is third most important cause disability-adjusted life-years globally. Unfortunately, treatment remains inadequate due to poor efficacy tolerability. There has been a failure translating promising preclinical drug targets into clinic use. This reflects challenges across whole development pathway, from models trial design. Nociceptors remain an attractive therapeutic target: their sensitization makes contribution many chronic states, they are located outside blood–brain barrier, relatively specific. The past decade seen significant advances techniques available study human nociceptors, including: use corneal confocal microscopy biopsy samples observe nociceptor morphology, culture nociceptors (either surgical or post-mortem tissue using induced pluripotent stem cell derived nociceptors), application high throughput technologies such as transcriptomics, vitro vivo electrophysiological characterization through microneurography, correlation with percepts provided by quantitative sensory testing. Genome editing cell-derived enables interrogation causal role genes regulation function. Both rodent more heterogeneous at molecular level than previously appreciated, while we find that there broad similarities between also differences involving ion channel function, expression, cellular excitability. These technological have emphasized maladaptive plastic changes occurring following injury contribute pain. Studying revealed new for suppression enhanced repair. Cellular enabled screening small molecule gene therapy approaches on some cases clinical outcomes. Undoubtedly, remain. Many these difficult implement scale, current differentiation protocols do not generate full diversity populations, still understanding inter-individual variation factors age, sex, ethnicity. We hope our ability directly investigate will only aid fundamental neurobiology underlying acute but help bridge translational gap.

Language: Английский

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Schwann cell endosome CGRP signals elicit periorbital mechanical allodynia in mice

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Feb. 3, 2022

Abstract Efficacy of monoclonal antibodies against calcitonin gene-related peptide (CGRP) or its receptor (calcitonin receptor-like receptor/receptor activity modifying protein-1, CLR/RAMP1) implicates peripherally-released CGRP in migraine pain. However, the site and mechanism CGRP-evoked peripheral pain remain unclear. By cell-selective RAMP1 gene deletion, we reveal that released from mouse cutaneous trigeminal fibers targets CLR/RAMP1 on surrounding Schwann cells to evoke periorbital mechanical allodynia. activation human generates long-lasting signals endosomes cAMP-dependent formation NO. NO, by gating cell transient potential ankyrin 1 (TRPA1), releases ROS, which a feed-forward manner sustain allodynia via nociceptor TRPA1. When encapsulated into nanoparticles release cargo acidified endosomes, antagonist provides superior inhibition signaling mice. Our data suggest CGRP-mediated neuronal/Schwann pathway mediates associated with neurogenic inflammation, contributing algesic action

Language: Английский

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Schwann cell functions in peripheral nerve development and repair

Neurobiology of Disease, Journal Year: 2022, Volume and Issue: 176, P. 105952 - 105952

Published: Dec. 7, 2022

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

Language: Английский

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Neuropathic pain caused by miswiring and abnormal end organ targeting

Nature, Journal Year: 2022, Volume and Issue: 606(7912), P. 137 - 145

Published: May 25, 2022

Abstract Nerve injury leads to chronic pain and exaggerated sensitivity gentle touch (allodynia) as well a loss of sensation in the areas which injured non-injured nerves come together 1–3 . The mechanisms that disambiguate these mixed paradoxical symptoms are unknown. Here we longitudinally non-invasively imaged genetically labelled populations fibres sense noxious stimuli (nociceptors) (low-threshold afferents) peripherally skin for longer than 10 months after nerve injury, while simultaneously tracking pain-related behaviour same mice. Fully denervated initially lost sensation, gradually recovered normal developed marked allodynia aversion several injury. This reinnervation-induced neuropathic involved nociceptors sprouted into territories precisely reproducing initial pattern innervation, were guided by blood vessels showed irregular terminal connectivity lowered activation thresholds mimicking low-threshold afferents. By contrast, afferents—which normally mediate intact 4–7 —did not reinnervate, leading an aberrant innervation tactile end organs such Meissner corpuscles with alone. Genetic ablation fully abrogated reinnervation allodynia. Our results thus reveal emergence form is driven structural plasticity, abnormal malfunction during reinnervation, provide mechanistic framework sensory manifestations observed clinically can impose heavy burden on patients.

Language: Английский

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A biopolymer-gated ionotronic junctionless oxide transistor array for spatiotemporal pain-perception emulation in nociceptor network

Nanoscale, Journal Year: 2022, Volume and Issue: 14(6), P. 2316 - 2326

Published: Jan. 1, 2022

Capable of reflecting the location and intensity external harmful stimuli, a nociceptor network is great importance for receiving pain-perception information. However, hardware-based implementation through use transistor array remains challenge in area brain-inspired neuromorphic applications. Herein, simple ionotronic junctionless oxide with abilities successfully realized due to coplanar-gate proton-coupling effect sodium alginate biopolymer electrolyte. Several important characteristics nociceptors are emulated, such as pain threshold, memory prior injury, sensitization behavior pathway alterations. In particular, good graded system has been established coplanar capacitance resistance. More importantly, clear polarity reversal Lorentz-type spatiotemporal emulation can be finally our projection-dependent network. This work may provide new avenues bionic medical machines humanoid robots based on these intriguing abilities.

Language: Английский

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