Targeting the hypothalamic a11 nucleus to treat parkinsonian-like nociceptive impairments

Charles KA(1)(2), Bouali-Benazzouz R(1)(2), Naudet F(1)(2), Aby F(1)(2), Fossat P(#)(1)(2), Benazzouz A(#)(3)(4).

Author information:
(1)Bordeaux University, Neurodegenerative Diseases Institute, UMR 5293,
Bordeaux, France.
(2)CNRS, Neurodegenerative Diseases Institute, UMR 5293, Bordeaux, France.
(3)Bordeaux University, Neurodegenerative Diseases Institute, UMR 5293,
Bordeaux, France. .
(4)CNRS, Neurodegenerative Diseases Institute, UMR 5293, Bordeaux, France.
.
(#)Contributed equally

Pain is a common non-motor symptom in Parkinson’s disease (PD), yet treatment
options remain limited due to incomplete understanding of underlying mechanisms.
Using the 6-hydroxydopamine (6-OHDA) rat model, we combined pharmacological,
behavioural, chemogenetic, electrophysiological, and immunohistochemical
approaches to investigate dopaminergic modulation of nociception by the
hypothalamic A11 projecting to the dorsal horn of the spinal cord (DHSC). We
demonstrate that A11 dopaminergic neurons are the sole source of dopamine in the
DHSC. Activation of both D1 and D2 receptors alleviated mechanical allodynia,
while only D2 receptor stimulation improved thermal hyperalgesia and normalized
wide dynamic range (WDR) neuron hyperexcitability. Selective chemogenetic
activation of the A11-DHSC pathway reduced nociceptive hypersensitivity and
improved WDR neuronal function in 6-OHDA rats. These findings establish a
critical role of spinal dopaminergic signaling in PD-related pain and highlight
the A11 region as a potential therapeutic target for pain management in PD.

© 2025. The Author(s).

DOI: 10.1038/s41531-025-01153-2
PMCID: PMC12595050
PMID: 41203633

Conflict of interest statement: Competing interests: The authors declare no
competing interests.

Auteurs Bordeaux Neurocampus