Neuron (Cambridge, Mass.), 2014-11, Vol.84 (4), p.821-834
2014
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- Autor(en) / Beteiligte
- Titel
- Descending Control of Itch Transmission by the Serotonergic System via 5-HT1A-Facilitated GRP-GRPR Signaling
- Ist Teil von
- Neuron (Cambridge, Mass.), 2014-11, Vol.84 (4), p.821-834
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2014
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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 Ca2+ 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. [Display omitted] •Central 5-HT signaling facilitates itch transmission•5-HT1A potentiates GRPR-mediated itch signaling•5-HT1A and GRPR are present in close proximity•Blockade of 5-HT1A function reduces chronic itch How does the itch-scratch cycle occur? Zhao et al. show that scratching of mice produces serotonin to inhibit pain; paradoxically, serotonin also enhances itch through a crosstalk between its receptor 5-HT1A and GRPR, an itch receptor in the spinal cord.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0896-6273eISSN: 1097-4199DOI: 10.1016/j.neuron.2014.10.003Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4254557
- Format
- –
- Schlagworte
- Action Potentials - drug effects, Action Potentials - physiology, Animals, Behavior, Calcium Signaling - physiology, Experiments, Gastrin-Releasing Peptide - metabolism, Male, Mice, Neurons, Neurons - drug effects, Neurons - metabolism, Pain, Physiology, Proteins, Pruritus - metabolism, Pruritus - physiopathology, Receptor, Serotonin, 5-HT1A - metabolism, Receptors, Bombesin - metabolism, Rodents, Signal Transduction - physiology, Spinal cord, Spinal Cord - drug effects, Spinal Cord - metabolism, Studies