| First Author | Ferreira N | Year | 2021 |
| Journal | Acta Neuropathol Commun | Volume | 9 |
| Issue | 1 | Pages | 31 |
| PubMed ID | 33632316 | Mgi Jnum | J:327681 |
| Mgi Id | MGI:6805833 | Doi | 10.1186/s40478-021-01131-8 |
| Citation | Ferreira N, et al. (2021) Trans-synaptic spreading of alpha-synuclein pathology through sensory afferents leads to sensory nerve degeneration and neuropathic pain. Acta Neuropathol Commun 9(1):31 |
| abstractText | Pain is a common non-motor symptom of Parkinson's disease (PD), with current limited knowledge of its pathophysiology. Here, we show that peripheral inoculation of mouse alpha-synuclein (alpha-Syn) pre-formed fibrils, in a transgenic mouse model of PD, elicited retrograde trans-synaptic spreading of alpha-Syn pathology (pSer129) across sensory neurons and dorsal nerve roots, reaching central pain processing regions, including the spinal dorsal horn and the projections of the anterolateral system in the central nervous system (CNS). Pathological peripheral to CNS propagation of alpha-Syn aggregates along interconnected neuronal populations within sensory afferents, was concomitant with impaired nociceptive response, reflected by mechanical allodynia, reduced nerve conduction velocities (sensory and motor) and degeneration of small- and medium-sized myelinated fibers. Our findings show a link between the transneuronal propagation of alpha-Syn pathology with sensory neuron dysfunction and neuropathic impairment, suggesting promising avenues of investigation into the mechanisms underlying pain in PD. |
