Format

Send to

Choose Destination
Dis Model Mech. 2019 Jun 27;12(6). pii: dmm039396. doi: 10.1242/dmm.039396.

Sensory neuropathy and nociception in rodent models of Parkinson's disease.

Author information

1
Institute of Clinical Pharmacology, Goethe-University Hospital, 60590 Frankfurt, Germany.
2
Experimental Neurology, Goethe-University Hospital, 60590 Frankfurt, Germany.
3
Institute of Clinical Pharmacology, Goethe-University Hospital, 60590 Frankfurt, Germany tegeder@em.uni-frankfurt.de.

Abstract

Parkinson's disease (PD) often manifests with prodromal pain and sensory losses whose etiologies are not well understood. Multiple genetic and toxicity-based rodent models of PD partly recapitulate the histopathology and motor function deficits. Although far less studied, there is some evidence that rodents, similar to humans, develop sensory manifestations of the disease, which may precede motor disturbances and help to elucidate the underlying mechanisms of PD-associated pain at the molecular and neuron circuit levels. The present Review summarizes nociception and other sensory functions in frequently used rodent PD models within the context of the complex phenotypes. In terms of mechanisms, it appears that the acute loss of dopaminergic neurons in systemic toxicity models (MPTP, rotenone) primarily causes nociceptive hyperexcitability, presumably owing to a loss of inhibitory control, whereas genetic models primarily result in a progressive loss of heat perception, reflecting sensory fiber neuropathies. At the molecular level, neither α-synuclein deposits alone nor failure of mitophagy alone appear to be strong enough to result in axonal or synaptic pathology of nociceptive neurons that manifest at the behavioral level, and peripheral sensory loss may mask central 'pain' in behavioral tests. Hence, allostatic combinations or additional challenges and novel behavioral assessments are needed to better evaluate PD-associated sensory neuropathies and pain in rodents.

KEYWORDS:

Mitogenesis; Mitophagy; Non-motor Parkinson's disease; Pain; Protein aggregate; Sensory neuropathy; Synuclein

Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

Publication type

Publication type

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center