Objective: We investigated the hypothesis that genotypes may influence pain phenotype in Parkinson’s disease (PD) patients. The presence of pain, its subtypes, severity, and time in relationship to PD onset and their relationship with genetic mutations in PD pathogenic genes were explored and reported.

Background: PD is a highly heterogeneous disorder in which genetic factors are likely to contribute to clinical variability, including susceptibility to non-motor symptoms such as pain (1,2). Pain is one of the most bothersome symptoms reported in PD, yet its underlying pathophysiological mechanisms are not well understood (3–7). PD-causative genes and their mutations have been related to different disease symptoms (8,9). To our understanding, pain prevalence and effects on quality of life in patients with monogenic forms of PD have not been systematically explored, and the data regarding that is scarce.

Method: This systematic literature review (PRISMA methodology) explored the association between monogenic forms of PD and pain, including SNCA, PRKN, PINK1, LRRK2, and DJ1 as monogenic PD genes and GBA1, ATP13A2, VPS35 gene as risk factors.

Results: We included sixty-five articles. Patients with PD monogenic mutations show overall high prevalence of pain with clear differences in terms of pain subtypes. Pain in general is most reported in PINK1 mutation carriers followed by patients with LRRK2 mutations, which is in several body parts for PINK1 PD patients and painful dystonia and higher pain threshold among LRRK2 ones. Painful dystonia, lower extremity pain, painful dystonic flexion on walking, and dorsal and upper back pain are frequently reported in SNCA carriers, while painful dystonia, and low back pain was reported as the most remarkable pain symptoms among PRKN carriers. Pain as an initial and severe symptom is also well described in GBA1-PD patients. There is limited and insufficient evidence to report on pain and ATP13A2, DJ1, and VPS35 mutations.

Conclusion: The current evidence suggests widespread prevalence of pain in patients with monogenic forms of PD including SNCA, PRKN, PINK1, LRRK2, and GBA1 genes. Pain may be a clinical marker of PD, preceding the onset of other motor symptoms in patients with PRKN and GBA1 mutations. Linking genetic profiles with pain in PD may have a meaningful clinical impact by orienting diagnostic test and ultimately, individualize treatment.

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