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Periaqueductal grey and spinal cord pathology contribute to pain in Parkinson’s disease by Yazead Buhidma; Carl Hobbs; Marzia Malcangio; Susan Duty is a Medicine article available to read on EtoBox.

What is Periaqueductal grey and spinal cord pathology contribute to pain in Parkinson’s disease about?

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 D~1~-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.

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Author

Yazead Buhidma; Carl Hobbs; Marzia Malcangio; Susan Duty

Publisher

Springer Science and Business Media LLC

Published

2023

Language

EN

Field

Medicine (Health Sciences)