ArticleNeuron2014
Descending control of itch transmission by the serotonergic system via 5-HT1A-facilitated GRP-GRPR signaling.
Article in Neuron, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed.
- Mechanisms of pruritus and advances in traditional Chinese medicine therapy (Review).Molecular medicine reports · 2026Review
- Aging Enhances Serotonergic Signaling via 5-HTAging cell · 2026Article
- From neuroimmune circuits to targeted therapy of chronic pruritus.Pharmacological reviews · 2026Review
- Central neural circuits underlying itch sensation.Nature reviews. Neuroscience · 2025Review
- Modulatory effects of bioactive natural compounds on pruritic pathways: mechanistic basis and therapeutic prospects.Inflammopharmacology · 2025Review
- Prevalence and Mechanisms of Itch in Chronic Wounds: A Narrative Review.Journal of clinical medicine · 2025Review
- AGS3-based optogenetic GDI induces GPCR-independent Gβγ signalling and macrophage migration.Open biology · 2025Article
- Cell Type-Specific Modulation of Acute Itch Processing in the Anterior Cingulate Cortex.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- AGS3-based optogenetic GDI induces GPCR-independent Gβγ signaling and macrophage migration.bioRxiv : the preprint server for biology · 2024Article
- Model of Chronic Itch in Aged Mice: Beneficial Effects of Drugs Affecting Descending Modulatory Systems.Acta dermato-venereologica · 2024Article
- Site-Specific Transient Receptor Potential Channel Mechanisms and Their Characteristics for Targeted Chronic Itch Treatment.Biomolecules · 2024Review
- Mechanism of medical hemorrhoid gel in relieving pruritus ani via inhibiting the activation of JAK2/STAT3 pathway.Frontiers in medicine · 2024Article
- Neural pathways that compel us to scratch an itch.Journal of biosciences · 2024Review
- Descending dopaminergic pathway facilitates itch signal processing via activating spinal GRPREMBO reports · 2023Article
- A review of psychocutaneous disorders from a psychotherapeutic perspective-Toolkit for the dermatologist.Skin health and disease · 2023Review
- Article
- Structures of human gastrin-releasing peptide receptors bound to antagonist and agonist for cancer and itch therapy.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Role of GRPR in Acupuncture Intervention in the "Itch-scratch Vicious Cycle" Spinal Circuit of Chronic Pruritus.Chinese medicine · 2023Review
- Critical Players and Therapeutic Targets in Chronic Itch.International journal of molecular sciences · 2022Review
- Identification and characterization of rostral ventromedial medulla neurons synaptically connected to the urinary bladder afferents in female rats with or without neonatal cystitis.The Journal of comparative neurology · 2022Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors.
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Abstract
Central serotonin (5-hydroxytryptophan, 5-HT) modulates somatosensory transduction, but how it achieves sensory modality-specific modulation remains unclear. Here we report that enhancing serotonergic tone via administration of 5-HT potentiates itch sensation, whereas mice lacking 5-HT or serotonergic neurons in the brainstem exhibit markedly reduced scratching behavior. Through pharmacological and behavioral screening, we identified 5-HT1A as a key receptor in facilitating gastrin-releasing peptide (GRP)-dependent scratching behavior. Coactivation of 5-HT1A and GRP receptors (GRPR) greatly potentiates subthreshold, GRP-induced Ca(2+) transients, and action potential firing of GRPR(+) neurons. Immunostaining, biochemical, and biophysical studies suggest that 5-HT1A and GRPR may function as receptor heteromeric complexes. Furthermore, 5-HT1A blockade significantly attenuates, whereas its activation contributes to, long-lasting itch transmission. Thus, our studies demonstrate that the descending 5-HT system facilitates GRP-GRPR signaling via 5-HT1A to augment itch-specific outputs, and a disruption of crosstalk between 5-HT1A and GRPR may be a useful antipruritic strategy. VIDEO ABSTRACT:
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