TY - JOUR
T1 - Periaqueductal grey and spinal cord pathology contribute to pain in Parkinson’s disease
AU - Buhidma, Yazead Buhidma
AU - Hobbs, Carl
AU - Malcangio, Marzia
AU - Duty, Susan
N1 - Funding Information:
We thank Parkinson’s UK and Queen Square Brain Banks for providing human tissue samples. We also thank Professor K R Chaudhuri for his insightful discussions into the clinical aspects of pain in Parkinson’s disease and Joane Lachica, Katerina Palios, and Joana Lama for assisting with image acquisition. The authors are in receipt of funding from the MRC-UK Doctoral Training [grant number MR/N013700/1].
Funding Information:
We thank Parkinson’s UK and Queen Square Brain Banks for providing human tissue samples. We also thank Professor K R Chaudhuri for his insightful discussions into the clinical aspects of pain in Parkinson’s disease and Joane Lachica, Katerina Palios, and Joana Lama for assisting with image acquisition. The authors are in receipt of funding from the MRC-UK Doctoral Training [grant number MR/N013700/1].
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/4/26
Y1 - 2023/4/26
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85154616512&partnerID=8YFLogxK
U2 - 10.1038/s41531-023-00510-3
DO - 10.1038/s41531-023-00510-3
M3 - Article
SN - 2373-8057
VL - 9
JO - npj Parkinson's Disease
JF - npj Parkinson's Disease
IS - 1
M1 - 69
ER -
