This study explores the sensory profile of the PINK1 knockout (KO) rat model to understand better non-dopaminergic contributions to PD-related pain and guide future therapeutic strategies.

Parkinson disease (PD) is a prevalent neurodegenerative disorder worldwide, yet no treatment prevents or cures PD, and many symptoms, including pain, remain undertreated. Pain is common and debilitating in PD, with limited relief from dopaminergic treatments, suggesting the involvement of non-dopaminergic neurotransmission systems.  In individuals with monogenic PD carrying a PTEN-induced putative kinase 1 (PINK1) mutation, abnormal sensorimotor profiles and pain manifestation have been observed, underscoring the need for preclinical models to investigate these mechanisms.

Mechanical sensitivity in PINK1 KO rats was compared wild-type (WT) controls. Using a presymptomatic age group (12±1 weeks) to assess pain independently of motor symptoms, male Long-Evans rats (N = 20) underwent behavioral testing including Von Frey test to measure mechanical allodynia (paw withdrawal thresholds: average, left, and right hind paw) and the open field and treadmill tests to assess motor behavior (locomotion, activity bouts, duration, distance, and velocity).

PINK1 KO rats exhibited significantly lower paw withdrawal thresholds, indicating increased mechanical sensitivity compared to WT controls. No significant differences in motor behavior were observed, and no correlation between mechanical sensitivity and motor outcomes was found.

These findings suggest that the PINK1 KO rat is a valuable tool for studying PD-related pain, particularly in the early stages. The model supports the hypothesis that changes in sensitivity to pain can be an onset symptom in PD and highlights the relevance of potentially exploring non-dopaminergic mechanisms of PD-related pain.