The Role of Serotonergic System in Parkinson’s Disease-Related Pain

AI Summary

Early dysfunction of brainstem serotonergic raphe nuclei disrupts descending spinal inhibition, increasing pain susceptibility in Parkinson's disease.
Serotonergic projections to supraspinal regions modulate the emotional and affective dimensions of pain, explaining co-occurrence of mood disturbances and pain in PD.
Clinical efficacy of SSRIs and other serotonin-targeting drugs supports therapeutic targeting of serotonergic mechanisms for mechanism-based PD pain treatments.

Neurosci Bull. 2026 Jun 11. doi: 10.1007/s12264-026-01649-8. Online ahead of print.

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.

PMID:42274907 | DOI:10.1007/s12264-026-01649-8

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