Intrinsic braking role of descending locus coeruleus noradrenergic neurons in acute and chronic itch in mice
Abstract Itch is defined as an unpleasant sensation that provokes a desire to scratch. Our understanding of neuronal circuits for itch information transmission and processing in the spinal dorsal horn (SDH) has progressively advanced following the identification of SDH neuron subsets that are crucia...
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| Format: | Article |
| Language: | English |
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BMC
2020-10-01
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| Series: | Molecular Brain |
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| Online Access: | http://link.springer.com/article/10.1186/s13041-020-00688-0 |
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| author | Keisuke Koga Yuto Shiraishi Ryo Yamagata Hidetoshi Tozaki-Saitoh Miho Shiratori-Hayashi Makoto Tsuda |
| author_facet | Keisuke Koga Yuto Shiraishi Ryo Yamagata Hidetoshi Tozaki-Saitoh Miho Shiratori-Hayashi Makoto Tsuda |
| author_sort | Keisuke Koga |
| collection | DOAJ |
| description | Abstract Itch is defined as an unpleasant sensation that provokes a desire to scratch. Our understanding of neuronal circuits for itch information transmission and processing in the spinal dorsal horn (SDH) has progressively advanced following the identification of SDH neuron subsets that are crucial for scratching behavior in models of itch. However, little is known about the control of acute and chronic itch by descending signals from the brain to the SDH. In this study, using genetic approaches that enable cell-type and circuit-specific functional manipulation, we reveal an intrinsic potential of locus coeruleus (LC)-noradrenergic (NAergic) neurons that project to the SDH to control acute and chronic itch. Activation and silencing of SDH-projecting LC-NAergic neurons reduced and enhanced scratching behavior, respectively, in models of histamine-dependent and -independent acute itch. Furthermore, in a model of chronic itch associated with contact dermatitis, repetitive scratching behavior was suppressed by the activation of the descending LC-NAergic pathway and by knocking out NA transporters specific to descending LC-NAergic neurons using a CRISPR-Cas9 system. Moreover, patch-clamp recording using spinal slices showed that noradrenaline facilitated inhibitory synaptic inputs onto gastrin-releasing peptide receptor-expressing SDH neurons, a neuronal subset known to be essential for itch transmission. Our findings suggest that descending LC-NAergic signaling intrinsically controls acute and chronic itch and provide potential therapeutic strategies for the treatment of acute and chronic itch. |
| first_indexed | 2024-12-23T05:17:55Z |
| format | Article |
| id | doaj.art-c7e706e7a38e415ebc08eddcec947222 |
| institution | Directory Open Access Journal |
| issn | 1756-6606 |
| language | English |
| last_indexed | 2024-12-23T05:17:55Z |
| publishDate | 2020-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Brain |
| spelling | doaj.art-c7e706e7a38e415ebc08eddcec9472222022-12-21T17:58:47ZengBMCMolecular Brain1756-66062020-10-0113111110.1186/s13041-020-00688-0Intrinsic braking role of descending locus coeruleus noradrenergic neurons in acute and chronic itch in miceKeisuke Koga0Yuto Shiraishi1Ryo Yamagata2Hidetoshi Tozaki-Saitoh3Miho Shiratori-Hayashi4Makoto Tsuda5Department of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu UniversityDepartment of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu UniversityDepartment of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu UniversityDepartment of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu UniversityDepartment of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu UniversityDepartment of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu UniversityAbstract Itch is defined as an unpleasant sensation that provokes a desire to scratch. Our understanding of neuronal circuits for itch information transmission and processing in the spinal dorsal horn (SDH) has progressively advanced following the identification of SDH neuron subsets that are crucial for scratching behavior in models of itch. However, little is known about the control of acute and chronic itch by descending signals from the brain to the SDH. In this study, using genetic approaches that enable cell-type and circuit-specific functional manipulation, we reveal an intrinsic potential of locus coeruleus (LC)-noradrenergic (NAergic) neurons that project to the SDH to control acute and chronic itch. Activation and silencing of SDH-projecting LC-NAergic neurons reduced and enhanced scratching behavior, respectively, in models of histamine-dependent and -independent acute itch. Furthermore, in a model of chronic itch associated with contact dermatitis, repetitive scratching behavior was suppressed by the activation of the descending LC-NAergic pathway and by knocking out NA transporters specific to descending LC-NAergic neurons using a CRISPR-Cas9 system. Moreover, patch-clamp recording using spinal slices showed that noradrenaline facilitated inhibitory synaptic inputs onto gastrin-releasing peptide receptor-expressing SDH neurons, a neuronal subset known to be essential for itch transmission. Our findings suggest that descending LC-NAergic signaling intrinsically controls acute and chronic itch and provide potential therapeutic strategies for the treatment of acute and chronic itch.http://link.springer.com/article/10.1186/s13041-020-00688-0Descending noradrenaline neuronsLocus coeruleusSpinal dorsal hornGastrin-releasing peptide receptor-expressing neuronsItchMouse |
| spellingShingle | Keisuke Koga Yuto Shiraishi Ryo Yamagata Hidetoshi Tozaki-Saitoh Miho Shiratori-Hayashi Makoto Tsuda Intrinsic braking role of descending locus coeruleus noradrenergic neurons in acute and chronic itch in mice Molecular Brain Descending noradrenaline neurons Locus coeruleus Spinal dorsal horn Gastrin-releasing peptide receptor-expressing neurons Itch Mouse |
| title | Intrinsic braking role of descending locus coeruleus noradrenergic neurons in acute and chronic itch in mice |
| title_full | Intrinsic braking role of descending locus coeruleus noradrenergic neurons in acute and chronic itch in mice |
| title_fullStr | Intrinsic braking role of descending locus coeruleus noradrenergic neurons in acute and chronic itch in mice |
| title_full_unstemmed | Intrinsic braking role of descending locus coeruleus noradrenergic neurons in acute and chronic itch in mice |
| title_short | Intrinsic braking role of descending locus coeruleus noradrenergic neurons in acute and chronic itch in mice |
| title_sort | intrinsic braking role of descending locus coeruleus noradrenergic neurons in acute and chronic itch in mice |
| topic | Descending noradrenaline neurons Locus coeruleus Spinal dorsal horn Gastrin-releasing peptide receptor-expressing neurons Itch Mouse |
| url | http://link.springer.com/article/10.1186/s13041-020-00688-0 |
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