Brainstem serotonin amplifies nociceptive transmission in a mouse model of Parkinson’s disease
Abstract Parkinson’s disease arises from the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to motor symptoms such as akinesia, rigidity, and tremor at rest. The non-motor component of Parkinson’s disease includes increased neuropathic pain, the prevalence of whi...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | npj Parkinson's Disease |
| Online Access: | https://doi.org/10.1038/s41531-024-00857-1 |
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| author | Zoé Grivet Franck Aby Aude Verboven Rabia Bouali-Benazzouz Benjamin Sueur François Maingret Frédéric Naudet Thibault Dhellemmes Philippe De Deurwaerdere Abdelhamid Benazzouz Pascal Fossat |
| author_facet | Zoé Grivet Franck Aby Aude Verboven Rabia Bouali-Benazzouz Benjamin Sueur François Maingret Frédéric Naudet Thibault Dhellemmes Philippe De Deurwaerdere Abdelhamid Benazzouz Pascal Fossat |
| author_sort | Zoé Grivet |
| collection | DOAJ |
| description | Abstract Parkinson’s disease arises from the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to motor symptoms such as akinesia, rigidity, and tremor at rest. The non-motor component of Parkinson’s disease includes increased neuropathic pain, the prevalence of which is 4 to 5 times higher than the general rate. By studying a mouse model of Parkinson’s disease induced by 6-hydroxydopamine, we assessed the impact of dopamine depletion on pain modulation. Mice exhibited mechanical hypersensitivity associated with hyperexcitability of neurons in the dorsal horn of the spinal cord (DHSC). Serotonin (5-HT) levels increased in the spinal cord, correlating with reduced tyrosine hydroxylase (TH) immunoreactivity in the nucleus raphe magnus (NRM) and increased excitability of 5-HT neurons. Selective optogenetic inhibition of 5-HT neurons attenuated mechanical hypersensitivity and reduced DHSC hyperexcitability. In addition, the blockade of 5-HT2A and 5-HT3 receptors reduced mechanical hypersensitivity. These results reveal, for the first time, that PD-like dopamine depletion triggers spinal-mediated mechanical hypersensitivity, associated with serotonergic hyperactivity in the NRM, opening up new therapeutic avenues for Parkinson’s disease-associated pain targeting the serotonergic systems. |
| format | Article |
| id | doaj-art-30028cfe99bd42989878299675419e71 |
| institution | Kabale University |
| issn | 2373-8057 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Parkinson's Disease |
| spelling | doaj-art-30028cfe99bd42989878299675419e712025-01-12T12:12:36ZengNature Portfolionpj Parkinson's Disease2373-80572025-01-0111111310.1038/s41531-024-00857-1Brainstem serotonin amplifies nociceptive transmission in a mouse model of Parkinson’s diseaseZoé Grivet0Franck Aby1Aude Verboven2Rabia Bouali-Benazzouz3Benjamin Sueur4François Maingret5Frédéric Naudet6Thibault Dhellemmes7Philippe De Deurwaerdere8Abdelhamid Benazzouz9Pascal Fossat10Université de Bordeaux, Institut des Maladies NeurodégénérativesUniversité de Bordeaux, Institut des Maladies NeurodégénérativesUniversité de Bordeaux, Institut des Maladies NeurodégénérativesUniversité de Bordeaux, Institut des Maladies NeurodégénérativesUniversité de Bordeaux, Institut des Maladies NeurodégénérativesUniversité de Bordeaux, Institut des Maladies NeurodégénérativesUniversité de Bordeaux, Institut des Maladies NeurodégénérativesUniversité de Bordeaux, Institut des Maladies NeurodégénérativesUniversité de Bordeaux, Institut des neurosciences cognitives et intégratives d’aquitaineUniversité de Bordeaux, Institut des Maladies NeurodégénérativesUniversité de Bordeaux, Institut des Maladies NeurodégénérativesAbstract Parkinson’s disease arises from the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to motor symptoms such as akinesia, rigidity, and tremor at rest. The non-motor component of Parkinson’s disease includes increased neuropathic pain, the prevalence of which is 4 to 5 times higher than the general rate. By studying a mouse model of Parkinson’s disease induced by 6-hydroxydopamine, we assessed the impact of dopamine depletion on pain modulation. Mice exhibited mechanical hypersensitivity associated with hyperexcitability of neurons in the dorsal horn of the spinal cord (DHSC). Serotonin (5-HT) levels increased in the spinal cord, correlating with reduced tyrosine hydroxylase (TH) immunoreactivity in the nucleus raphe magnus (NRM) and increased excitability of 5-HT neurons. Selective optogenetic inhibition of 5-HT neurons attenuated mechanical hypersensitivity and reduced DHSC hyperexcitability. In addition, the blockade of 5-HT2A and 5-HT3 receptors reduced mechanical hypersensitivity. These results reveal, for the first time, that PD-like dopamine depletion triggers spinal-mediated mechanical hypersensitivity, associated with serotonergic hyperactivity in the NRM, opening up new therapeutic avenues for Parkinson’s disease-associated pain targeting the serotonergic systems.https://doi.org/10.1038/s41531-024-00857-1 |
| spellingShingle | Zoé Grivet Franck Aby Aude Verboven Rabia Bouali-Benazzouz Benjamin Sueur François Maingret Frédéric Naudet Thibault Dhellemmes Philippe De Deurwaerdere Abdelhamid Benazzouz Pascal Fossat Brainstem serotonin amplifies nociceptive transmission in a mouse model of Parkinson’s disease npj Parkinson's Disease |
| title | Brainstem serotonin amplifies nociceptive transmission in a mouse model of Parkinson’s disease |
| title_full | Brainstem serotonin amplifies nociceptive transmission in a mouse model of Parkinson’s disease |
| title_fullStr | Brainstem serotonin amplifies nociceptive transmission in a mouse model of Parkinson’s disease |
| title_full_unstemmed | Brainstem serotonin amplifies nociceptive transmission in a mouse model of Parkinson’s disease |
| title_short | Brainstem serotonin amplifies nociceptive transmission in a mouse model of Parkinson’s disease |
| title_sort | brainstem serotonin amplifies nociceptive transmission in a mouse model of parkinson s disease |
| url | https://doi.org/10.1038/s41531-024-00857-1 |
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