Postnatal maturation of spinal dynorphin circuits and their role in somatosensation DOI
Chelsie L. Brewer, Lauren Styczynski, Elizabeth K. Serafin

et al.

Pain, Journal Year: 2020, Volume and Issue: 161(8), P. 1906 - 1924

Published: April 1, 2020

Abstract Inhibitory interneurons in the adult spinal dorsal horn (DH) can be neurochemically classified into subpopulations that regulate distinct somatosensory modalities. Although inhibitory networks rodent DH undergo dramatic remodeling over first weeks of life, little is known about maturation identified classes GABAergic interneurons, or whether their role somatosensation shifts during development. We investigated age-dependent changes connectivity and function prodynorphin (DYN)-lineage neurons mouse suppress mechanosensation itch adulthood. In vitro patch clamp recordings revealed a developmental increase primary afferent drive to DYN transition from exclusive C-fiber monosynaptic input mixed A-fiber innervation. most exhibited tonic firing as expected phenotype, neonatal adolescent cells were predominantly phasic single-spiking. Importantly, we also found presynaptic terminals contacting lamina I spinoparabrachial projection (PNs) originate neurons. Furthermore, synaptic onto PNs was weaker period, likely reflecting lower number reduced probability GABA release compared adults. Finally, attenuated mechanical sensitivity throughout development, but this population dampened acute nonhistaminergic only Collectively, these findings suggest “gates” controlling sensory transmission brain may emerge modality-selective manner early life due postnatal tuning circuits within DH.

Language: Английский

Mechanical Allodynia Circuitry in the Dorsal Horn Is Defined by the Nature of the Injury DOI Creative Commons
Cédric Peirs, Sean-Paul G. Williams, Xinyi Zhao

et al.

Neuron, Journal Year: 2020, Volume and Issue: 109(1), P. 73 - 90.e7

Published: Nov. 11, 2020

Language: Английский

Citations

152
Central circuit mechanisms of itch DOI Creative Commons
Xiaojun Chen, Yan-Gang Sun

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: June 16, 2020

Abstract Itch, in particular chronic forms, has been widely recognized as an important clinical problem, but much less is known about the mechanisms of itch comparison with other sensory modalities such pain. Recently, considerable progress made dissecting circuit at both spinal and supraspinal levels. Major components neural underlying chemical mechanical have now identified, along circuits relaying ascending transmission descending modulation itch. In this review, we summarize elucidating mechanism

Language: Английский

Citations

118
Recent advances in our understanding of the organization of dorsal horn neuron populations and their contribution to cutaneous mechanical allodynia DOI Creative Commons
Cédric Peirs, Radhouane Dallel, Andrew J. Todd

et al.

Journal of Neural Transmission, Journal Year: 2020, Volume and Issue: 127(4), P. 505 - 525

Published: April 1, 2020

Abstract The dorsal horns of the spinal cord and trigeminal nuclei in brainstem contain neuron populations that are critical to process sensory information. Neurons these areas highly heterogeneous their morphology, molecular phenotype intrinsic properties, making it difficult identify functionally distinct cell populations, determine how engaged pathophysiological conditions. There is a growing consensus concerning classification based on transcriptomic transductomic analyses horn. These approaches have led discovery several molecularly defined types been implicated cutaneous mechanical allodynia, prevalent difficult-to-treat symptom chronic pain, which touch becomes painful. main objective this review provide contemporary view horn neuronal describe recent advances our understanding they participate allodynia.

Language: Английский

Citations

99
Differential Coding of Itch and Pain by a Subpopulation of Primary Afferent Neurons DOI Creative Commons
Behrang Sharif,

Ariel R. Ase,

Alfredo Ribeiro‐da‐Silva

et al.

Neuron, Journal Year: 2020, Volume and Issue: 106(6), P. 940 - 951.e4

Published: April 15, 2020

Language: Английский

Citations

89
Neural Mechanisms of Itch DOI Open Access
Mark C. Lay, Xinzhong Dong

Annual Review of Neuroscience, Journal Year: 2020, Volume and Issue: 43(1), P. 187 - 205

Published: Feb. 20, 2020

Itch is a unique sensation that helps organisms scratch away external threats; scratching itself induces an immune response can contribute to more itchiness. induced chemically in the peripheral nervous system via wide array of receptors. Given superficial localization itch neuron terminals, cells dwell close skin significantly itch. Certain mechanical stimuli mediated by recently discovered circuits also sensation. Ultimately, spinal cord, and likely brain, mediate touch, pain, engage cross modulation. Much perception still mystery, but we present this review known ligands receptors associated with We describe experiments findings from investigations into supraspinal circuitry responsible for

Language: Английский

Citations

75
Exploration of sensory and spinal neurons expressing gastrin-releasing peptide in itch and pain related behaviors DOI Creative Commons
Devin M. Barry, Xueting Liu, Benlong Liu

et al.

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: March 13, 2020

Abstract Gastrin-releasing peptide (GRP) functions as a neurotransmitter for non-histaminergic itch, but its site of action (sensory neurons vs spinal cord) remains controversial. To determine the role GRP in sensory neurons, we generated floxed Grp mouse line. We found that conditional knockout results attenuated without impairing histamine-induced itch. Using -Cre knock-in line, show upper epidermis skin is exclusively innervated by fibers, whose activation via optogeneics and chemogenetics evokes itch- not pain-related scratching or wiping behaviors. In contrast, intersectional genetic ablation does affect itch nor pain transmission, demonstrating are dispensable transmission. These data indicate neuropeptide dedicated to

Language: Английский

Citations

71
A neuropeptide code for itch DOI

Zhou‐Feng Chen

Nature reviews. Neuroscience, Journal Year: 2021, Volume and Issue: 22(12), P. 758 - 776

Published: Oct. 18, 2021

Language: Английский

Citations

58
A gut-secreted peptide suppresses arousability from sleep DOI Creative Commons
Iris Titos, Alen Juginović, Alexandra Vaccaro

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(7), P. 1382 - 1397.e21

Published: March 1, 2023

Language: Английский

Citations

37
Pain persists in mice lacking both Substance P and CGRPα signaling DOI Creative Commons
Donald Iain MacDonald, Monessha Jayabalan,

Jonathan Seaman

et al.

eLife, Journal Year: 2025, Volume and Issue: 13

Published: March 18, 2025

The neuropeptides Substance P and CGRPα have long been thought important for pain sensation. Both peptides their receptors are expressed at high levels in pain-responsive neurons from the periphery to brain making them attractive therapeutic targets. However, drugs targeting these pathways individually did not relieve clinical trials. Since extensively co-expressed, we hypothesized that simultaneous inhibition would be required effective analgesia. We therefore generated Tac1 Calca double knockout (DKO) mice assessed behavior using a wide range of pain-relevant assays. As expected, were undetectable throughout nervous system DKO mice. To our surprise, animals displayed largely intact responses mechanical, thermal, chemical, visceral stimuli, as well itch. Moreover, chronic inflammatory neurogenic inflammation unaffected by loss two peptides. Finally, neuropathic evoked nerve injury or chemotherapy treatment was also preserved peptide-deficient Thus, results demonstrate even combination, transmission acute pain.

Language: Английский

Citations

1
Resolvin D3 controls mouse and human TRPV1-positive neurons and preclinical progression of psoriasis DOI Creative Commons
Sang Hoon Lee, Raquel Tonello, Sang-Taek Im

et al.

Theranostics, Journal Year: 2020, Volume and Issue: 10(26), P. 12111 - 12126

Published: Jan. 1, 2020

Psoriasis is a chronic inflammatory disease caused by complex interplay between the immune and nervous systems with recurrent scaly skin plaques, thickened stratum corneum, infiltration activation of cells, itch. Despite an increasing availability therapies, they often have adverse effects, high costs, dissociated effects on inflammation Activation sensory neurons innervating TRPV1 (transient receptor potential vanilloid 1) are emerging as critical components in pathogenesis psoriasis, but little known about their endogenous inhibitors. Recent studies demonstrated that resolvins, lipid mediators derived from omega-3 fatty acids, potent inhibitors TRP channels may offer new therapies for psoriasis without effects.

Language: Английский

Citations

58