The characterization of Parkinson's disease related pain based on the classification system: The severity of neuropathic pain and the clinical profile of nociplastic pain.

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IntroductionPain significantly impairs quality of life in Parkinson's disease (PD). While the PD Pain Classification System (PD-PCS) categorizes PD-related pain into nociceptive, neuropathic, and nociplastic pain, the clinical and structural correlates of these subtypes, particularly nociplastic pain, remain poorly characterized. The objective of this study was to elucidate the distinct features of each PD-related pain subtype.MethodsThis single-center cross-sectional study involved a two-stage PD-PCS-based evaluation. First, 192 PD patients were assessed for the prevalence of pain subtypes and their associations with demographic and clinical variables. Second, 40 PD patients with pain underwent detailed physician-led assessments using validated motor and non-motor scales, including MDS-UPDRS, KPPS, KPPQ, NMSS, HADS, PDSS-2, PDQ-8, WOQ-9, and VAS. Structural and diffusion MRI analyses, including free-water imaging and neurite orientation dispersion and density imaging, were performed in a subset of participants to explore pain-related neural correlates.ResultsAmong 192 PD patients in the first survey, 107 (55.7%) reported pain, classified as nociceptive (37.4%), neuropathic (18.7%), nociplastic (23.4%), or PD-unrelated pain (20.6%). Compared with nociplastic pain, neuropathic pain showed higher PD-PCS scores (39.8 ± 29.2 vs 14.3 ± 16.9; p = 0.0014) and higher King's Parkinson's Pain Questionnaire scores (5.8 ± 2.7 vs 2.9 ± 1.5; p = 0.00014). Compared with nociceptive pain, neuropathic pain also showed higher questionnaire scores (5.8 ± 2.7 vs 3.8 ± 2.1; p = 0.013). In the second survey, neuropathic pain was associated with greater motor complications than nociplastic pain (MDS-UPDRS Part IV: 10.2 ± 2.9 vs 3.9 ± 3.4; p = 0.029). In the supplementary MRI analysis, neuropathic pain showed distinct microstructural abnormalities in pain-processing neural networks. Conversely, nociplastic pain showed no distinctive motor/non-motor features or detectable MRI abnormalities, despite a comparable negative impact on quality of life.ConclusionNeuropathic pain in PD represents a severe phenotype linked to both motor fluctuations and structural brain changes, underscoring the need for mechanism-specific management strategies. By contrast, the absence of defining clinical or structural markers in nociplastic pain highlights it diagnostic challenge and suggests that current assessment tools may insufficiently capture this pain mechanism. These findings emphasize the need for multidimensional and mechanism-oriented approaches to PD-related pain in clinical practice.

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