Parabrachial Npy1r-Expressing Neurons Drive Pain in a Mouse Model of Parkinson's Disease.

BACKGROUND

Pain is a common and debilitating non-motor symptom of Parkinson's disease (PD), yet its underlying neural mechanisms remain poorly defined.

OBJECTIVES

The aim was to test whether neuropeptide Y Y1 receptor (Npy1r)-expressing parabrachial neuronsdrive PD-associated pain.

METHODS

In a unilateral 6 hydroxydopamine (6-OHDA) mouse model, pain-related behaviors, neuronal activation, and intrinsic excitability of parabrachial nucleus (PBN) neurons were assessed using behavioral assays, fluorescence in situ hybridization, and ex vivo whole-cell patch-clamp electrophysiology. Cell type-specific chemogenetic inhibition.

RESULTS

Following 6-OHDA injection, mice developed robust multimodal hypersensitivity accompanied by increased recruitment of Npy1r-expressing PBN neurons. Chemogenetic silencing of Npy1r-expressing PBN neurons abolished PD-associated hypersensitivity, whereas activation induced pain-like behaviors in naïve mice.

CONCLUSIONS

Npy1r-expressing PBNs are a discrete supraspinal population that drives pain in a preclinical model of PD. © 2026 International Parkinson and Movement Disorder Society.