TOBeATPAIN Project 1: Neuroinflammation and pain in Alzheimer’s disease

Health

TOBeATPAIN Project 1: Neuroinflammation and pain in Alzheimer’s disease

The perception of pain is altered in AD patients and poor management of pain in conditions such as chronic inflammation may trigger distress and aggressiveness. Systemic inflammation is a major risk factor for the development of AD and the response of brain-resident microglia to systemic inflammation can exacerbate neuroinflammation. This project proposes that systemic inflammation affects (micro)glial activity in AD brain/cord pain pathways and alters pain perception.

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 1 will:

Assess acute and inflammatory pain (K/BxN model of human inflammatory arthritis) in AD mice: combine pain-like and cognitive behaviour;
Examine (micro)glial activity and effect of glial inhibitors (e.g. P2X7 or CX3CR1 antagonists) on pain pathways activation in brain and spinal cord by combining: 24 hours continued EEG and power spectrum analysis, (TSPO)microPET imaging, autoradiography and immunohistochemistry (IHC), and cyto(chemo)kine tissue levels (ELISA);
Examine (micro)glial activity in post-mortem brain and spinal cord tissue from AD patients with and without systemic inflammation (IHC); and 4) examine pain response to different stimuli: fMRI response to pain and amelioration with single dose of analgesics in early AD patients.

Expected results

Definition of the impact of (micro)glia and cyto(chemo)kine inhibitors on the activity of key pain regions.
Definition of (micro)glial phenotype under peripheral inflammation and AD pathology.
Development of a translational mouse model for the effect of pain control on cognition deficits in AD.

Secondment(s): Eli Lilly (6 months). Examine CNS parameters by EEG in AD mice during systemic inflammation, and training on product development strategy, product launch & management and public relations.