Early Pain and Sensory Dysfunction in Drug-Naïve Parkinson's Disease: Evidence From Quantitative Sensory Testing

Pain and sensory disturbances are common non-motor symptoms in Parkinson's disease (PD) and can occur early in the disease course, even before starting dopaminergic treatment. However, somatosensory abnormalities in drug-naïve PD remain insufficiently characterized, particularly in the absence of dopaminergic medication effects.

In this cross-sectional study, 35 people with drug-naïve PD (PwP) and 35 individually age- and sex-matched healthy controls underwent quantitative sensory testing (QST). Testing included brush stimulation to assess dynamic mechanical allodynia (DMA), pinprick stimulation to assess mechanical pain sensitivity-both rated using a numeric rating scale (NRS)-and pressure pain threshold (PPT) measurements. PwP were stratified by daily pain status. Data were analysed using linear mixed-effects models (LMEMs) that accounted for matching and repeated measures.

Pinprick stimulation revealed statistically significant mechanical hyperalgesia across all tested body regions in PwP, regardless of pain status, compared with healthy controls. PPT testing demonstrated significantly lower thresholds in PwP across most body regions, indicating early pressure hyperalgesia. In contrast, brush testing did not reveal significant group differences, and only a small proportion of PwP showed signs of DMA. No significant differences were observed between PwP with and without pain, nor between the disease-onset side and the contralateral side.

Drug-naïve PD is characterized by early nociceptive sensory abnormalities, with consistent evidence of mechanical hyperalgesia even in patients without chronic pain. The absence of DMA suggests that nociceptive hypersensitivity may precede alterations in non-nociceptive processing. Nociceptive QST measures may therefore represent indicators of altered sensory processing in early-stage PwP.

This study adds to existing evidence that sensory disturbances, including pain, may be present already in the early, drug-naïve stages of Parkinson's disease. Clinically, these findings highlight the importance of recognizing pain and sensory abnormalities as potential early non-motor features of PD, including before dopaminergic treatment is initiated.