Dor na Doença de Parkinson: neurobiologia translacional e fenotipagem mecanística

Parkinson's disease (PD) is a progressive neurodegenerative disorder in which pain is a frequent, heterogeneous, and potentially disabling non-motor manifestation. This article examines pain in PD through an interdisciplinary Medicine–Nursing–Neuroscience perspective and proposes an integrative conceptual model linking molecular vulnerability to clinical phenotype: GBA1–glucocerebrosidase (GCase)–lysosomal homeostasis–alpha-synuclein neurotransmitter-system dysfunction adaptive or maladaptive neuroplasticity pain processing clinical phenotyping through MIADOR-DP. An integrative theoretical review was conducted, incorporating evidence on pain mechanisms, dopaminergic and non-dopaminergic systems, neuroplasticity, BDNF, GBA1, Gaucher disease, lysosomal function, and PD-specific pain assessment tools. Evidence strongly supports links among GBA1 variants, reduced GCase activity, lysosomal dysfunction, and alpha-synuclein accumulation in PD pathogenesis, but does not establish this pathway as a sole cause of pain. Studies of monogenic PD suggest that GBA1 carriers may exhibit distinctive pain profiles, although current data are heterogeneous. We therefore distinguish an upstream biological layer of neurodegenerative vulnerability from a downstream phenotypic layer in which dopaminergic, serotonergic, noradrenergic, glutamatergic, GABAergic, and opioid alterations interact with neuroplastic mechanisms and clinical modifiers. Within this framework, MIADOR-DP is positioned as a potential clinical pain-phenotyping tool rather than a molecular biomarker. Integrating lysosomal biology, neurotransmitter networks, neuroplasticity, and mechanism-based assessment may improve understanding of pain heterogeneity in PD and generate testable hypotheses for validation studies and precision medicine.