Somatosensory processing in a German family with PINK1 mutations: its potential role in Parkinson disease

Abstract

Background: It is unclear whether sensory symptoms in Parkinson disease (PD) are of primary or of secondary origin attributable to motor symptoms such as rigidity and bradykinesia.Objective: The aim of this study was to elucidate whether sensory abnormalities are present and may precede motor symptoms in familial parkinsonism by characterizing sensory function in symptomatic and asymptomatic PINK1 mutation carriers. Methods: Fourteen family members with PINK1 mutation and 14 healthy controls were examined clinically, with nerve conduction studies and quantitative sensory testing (QST). Results: Thresholds for mechanical detection, mechanical pain and pressure pain were higher in PINK1 mutation carriers compared to controls. Higher thresholds for mechanical detection, mechanical pain and pressure pain were even found in asymptomatic, clinically not or only mildly affected PINK1 mutation carriers. Conclusions: Data suggest that PINK1-associated PD is associated with a primary hypofunction of nociceptive and non-nociceptive afferent systems that can already be found at the time when motor signs of PD are only subtle. As nerve conduction studies did not reveal differences between PINK1 mutation carriers and controls, we propose that the somatosensory impairment is related to abnormal central somatosensory processing.

Somatosensory function in asymptomatic Parkin‐mutation carriers

“…However, normal neurography favours the view that neuropathy is probably not a feature preceding motor symptoms in Parkin ‐associated PD but rather a secondary phenomenon. In line with other studies, our data rather support the view of a central origin of somatosensory disturbances in PD [3, 12, 13].…”

Decreased and increased cerebral regional homogeneity in early Parkinson's disease

“…Early stage PD patients also showed severely depressed responses to sensory stimuli (Rossini et al, 1998). Even in genetically controlled familial PD cases, somatosensory hypofunction was detectable at the time with subtle motor-symptoms (Gierthmuhlen et al, 2009). Sensory disturbance in early Parkinson's disease patients is caused by cutaneous denervation (Nolano et al, 2008).…”

Potential of animal models for advancing the understanding and treatment of pain in Parkinson’s disease

“…19 More clarification is therefore awaited on the potential link between GBA mutations and pain. Abnormalities of nociceptive processing reportedly also occur in PINK1 (gene encoding a mitochondrial serine/threonine-protein kinase) mutation carriers, although in this instance the mutation appears to lead to hypoalgesia when compared to non-PD controls, 20 rather than the hyperalgesia noted in sporadic PD cases. Future investigation into the reason behind this switch in phenotype may be informative in relation to the pathophysiology of pain in PD.…”