TOBeATPAIN Project 2: Neuroinflammation and pain in Parkinson’s disease

Health

TOBeATPAIN Project 2: Neuroinflammation and pain in Parkinson’s disease

Pain is one of the non-motor signs of Parkinson’s disease (PD), poorly understood and inadequately treated by current analgesics in patients. Neuropathology certainly extends from brain into the spinal cord; alpha-synuclein immunoreactive inclusions are found in nociceptive neurons of the dorsal horn in confirmed cases of PD. Whilst neuroinflammation is implicated in the neurodegenerative side of PD, its involvement in PD pain is unexplored. This project proposes that micro(glia) activity in descending pathways from the brain modulates pain signalling at spinal cord level contributing to pain in PD.

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No 764860.

Aims

ESR 2 will:

Apply mouse models of PD (toxin, proteasome inhibitor and alpha-synuclein transgenic models) to assess pain sensitivity and(micro)glial and neuronal activation in pain pathways by microPET imaging, autoradiography and immunohistochemistry (IHC), and quantify cyto(chemo)kines tissue levels by ELISA;
Examine the extent of (micro)glia activation in post-mortem brain and spinal cord tissue (IHC) from PD patients with confirmed pain and mouse spinal cord slice electrophysiology;
Examine the efficacy of established anti-inflammatory agents and (micro)glia inhibitors on relieving pain in PD mice; and
Examine pain response to different stimuli: fMRI response to pain and acute amelioration with single dose of different analgesics in PD patients.

Expected results

Definition of the impact of cyto(chemo)kines onto key pain pathways in the brain and spinal cord of PD mouse models and autopsy samples from PD patients.
Analgesic efficacy of anti-inflammatory/(micro)glia inhibitor agents in PD mouse models expressing pain. Efficacy of analgesics on acute pain response in PD patients.

Secondment(s): Eli Lilly (4 months). Examine the extent of (micro)glia activation in mouse PD models using biochemical and IHC methods and measurements on spinal cord excitability in spinal cord slices from PD models. Training on product development strategy, product launch & management and public relations. UKW (2 months). Analysis of PD skin biopsies for inflammatory mediators detected in mouse models.