Yi‑Zhi Song1,2 · Yan‑Qin Shen1,2,3

1 Laboratory of Neurodegenerative Disease, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China 

2 MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China 

3 Wuxi Central Rehabilitation Hospital, Affiliated Mental Health Centre of Jiangnan University, Wuxi 214000, China

Abstract

Pain affects up to 85% of Parkinson’s disease (PD) patients, but treatment options remain limited. The brainstem serotonergic raphe nuclei, as the main source of central serotonin, dysfunction early in PD. Serotonin mediates descending pain inhibition to the spinal cord, and disruption of this pathway likely increases pain susceptibility. Concurrently, serotonergic projections to supraspinal regions shape the emotional-affective dimension of pain, which may explain why mood disturbances and pain often co-occur in PD. Clinically, selective serotonin reuptake inhibitors (SSRIs) and other serotonin-targeting drugs show efficacy in both PD depression and chronic pain conditions. This review synthesizes current evidence on serotonergic mechanisms in PD pain and identifies potential therapeutic targets, thereby providing a foundation for mechanism-based treatment strategies.

Keywords

Serotonin; Parkinson’s disease; Chronic pain; Neurodegenerative disease; Gut-brain axis

[SpringerLink]