Periaqueductal grey and spinal cord pathology contribute to pain in Parkinson’s disease
Abstract Pain is a key non-motor feature of Parkinson’s disease (PD) that significantly impacts on life quality. The mechanisms underlying chronic pain in PD are poorly understood, hence the lack of effective treatments. Using the 6-hydroxydopamine (6-OHDA) lesioned rat model of PD, we identified re...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-04-01
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| Series: | npj Parkinson's Disease |
| Online Access: | https://doi.org/10.1038/s41531-023-00510-3 |
| _version_ | 1797422224511074304 |
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| author | Yazead Buhidma Carl Hobbs Marzia Malcangio Susan Duty |
| author_facet | Yazead Buhidma Carl Hobbs Marzia Malcangio Susan Duty |
| author_sort | Yazead Buhidma |
| collection | DOAJ |
| description | Abstract Pain is a key non-motor feature of Parkinson’s disease (PD) that significantly impacts on life quality. The mechanisms underlying chronic pain in PD are poorly understood, hence the lack of effective treatments. Using the 6-hydroxydopamine (6-OHDA) lesioned rat model of PD, we identified reductions in dopaminergic neurons in the periaqueductal grey (PAG) and Met-enkephalin in the dorsal horn of the spinal cord that were validated in human PD tissue samples. Pharmacological activation of D1-like receptors in the PAG, identified as the DRD5+ phenotype located on glutamatergic neurons, alleviated the mechanical hypersensitivity seen in the Parkinsonian model. Downstream activity in serotonergic neurons in the Raphé magnus (RMg) was also reduced in 6-OHDA lesioned rats, as detected by diminished c-FOS positivity. Furthermore, we identified increased pre-aggregate α-synuclein, coupled with elevated activated microglia in the dorsal horn of the spinal cord in those people that experienced PD-related pain in life. Our findings have outlined pathological pathways involved in the manifestation of pain in PD that may present targets for improved analgesia in people with PD. |
| first_indexed | 2024-03-09T07:29:08Z |
| format | Article |
| id | doaj.art-529a2b31bfa54e9697fb635b16940aa6 |
| institution | Directory Open Access Journal |
| issn | 2373-8057 |
| language | English |
| last_indexed | 2024-03-09T07:29:08Z |
| publishDate | 2023-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Parkinson's Disease |
| spelling | doaj.art-529a2b31bfa54e9697fb635b16940aa62023-12-03T06:44:59ZengNature Portfolionpj Parkinson's Disease2373-80572023-04-019111410.1038/s41531-023-00510-3Periaqueductal grey and spinal cord pathology contribute to pain in Parkinson’s diseaseYazead Buhidma0Carl Hobbs1Marzia Malcangio2Susan Duty3King’s College London, Institute of Psychiatry, Psychology & Neuroscience, Wolfson Centre for Age-Related DiseasesKing’s College London, Institute of Psychiatry, Psychology & Neuroscience, Wolfson Centre for Age-Related DiseasesKing’s College London, Institute of Psychiatry, Psychology & Neuroscience, Wolfson Centre for Age-Related DiseasesKing’s College London, Institute of Psychiatry, Psychology & Neuroscience, Wolfson Centre for Age-Related DiseasesAbstract Pain is a key non-motor feature of Parkinson’s disease (PD) that significantly impacts on life quality. The mechanisms underlying chronic pain in PD are poorly understood, hence the lack of effective treatments. Using the 6-hydroxydopamine (6-OHDA) lesioned rat model of PD, we identified reductions in dopaminergic neurons in the periaqueductal grey (PAG) and Met-enkephalin in the dorsal horn of the spinal cord that were validated in human PD tissue samples. Pharmacological activation of D1-like receptors in the PAG, identified as the DRD5+ phenotype located on glutamatergic neurons, alleviated the mechanical hypersensitivity seen in the Parkinsonian model. Downstream activity in serotonergic neurons in the Raphé magnus (RMg) was also reduced in 6-OHDA lesioned rats, as detected by diminished c-FOS positivity. Furthermore, we identified increased pre-aggregate α-synuclein, coupled with elevated activated microglia in the dorsal horn of the spinal cord in those people that experienced PD-related pain in life. Our findings have outlined pathological pathways involved in the manifestation of pain in PD that may present targets for improved analgesia in people with PD.https://doi.org/10.1038/s41531-023-00510-3 |
| spellingShingle | Yazead Buhidma Carl Hobbs Marzia Malcangio Susan Duty Periaqueductal grey and spinal cord pathology contribute to pain in Parkinson’s disease npj Parkinson's Disease |
| title | Periaqueductal grey and spinal cord pathology contribute to pain in Parkinson’s disease |
| title_full | Periaqueductal grey and spinal cord pathology contribute to pain in Parkinson’s disease |
| title_fullStr | Periaqueductal grey and spinal cord pathology contribute to pain in Parkinson’s disease |
| title_full_unstemmed | Periaqueductal grey and spinal cord pathology contribute to pain in Parkinson’s disease |
| title_short | Periaqueductal grey and spinal cord pathology contribute to pain in Parkinson’s disease |
| title_sort | periaqueductal grey and spinal cord pathology contribute to pain in parkinson s disease |
| url | https://doi.org/10.1038/s41531-023-00510-3 |
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