Pain in Parkinson's Disease: Exploration of the Serotonin System in Positron Emission Tomography (PET [18F]-MPPF)

The prevalence of chronic pain in PD can be estimated at 60-80% from several epidemiological studies. Both semiological and pathophysiological classification proposes specific and non-specific pain in PD. While non-specific pain is not directly related to PD but may be aggravated by the disease, specific pain is a direct result of the disease with dystonic pain characterized by painful cramps in relation to motor symptoms and non-systematic central pain such as burning, paresthesia, compression (central parkinsonian pain). A case-control study reported that cramp-like pain and central pain were three times more frequent in parkinsonian patients than in the general population. Pathophysiologically, several studies suggest an abnormal nociceptive integration process in PD patients. Previous studies have indicated that the nociceptive signal is amplified along the pain transmission pathways. This could be related to increased facilitation through central sensitization of pain pathways or decreased inhibition (reduced activity of descending inhibitory control systems). Several recent studies suggest that the noradrenergic and/or serotonergic systems may be involved in the pathophysiology of PD-related pain. Therefore, this project will explore the involvement of the serotonergic system in the pathophysiology of pain using brain neuroimaging in PD patients with central pain.

The present study hypothesize that the binding of the radiotracer [18F]-MPPF, allowing in vivo imaging of 5HT1A receptors, will be reduced in PD patients with central pain compared to non-painful PD patients at the level of the median raphe, but also at the level of several brain structures involved in the pain matrix such as the insula, the anterior and posterior cingulate cortex, the orbitofrontal cortex, etc. A correlation between the clinical parameters of pain and the brain structures in which MRP binding is decreased should make it possible to confirm the link between these serotonin binding anomalies and pain. Finally, the morphological and functional MRI study should make it possible to identify structural and functional abnormalities within the pain networks in painful Parkinson's patients.

Inclusion criteria

• Patients with PD defined according to United Kingdom Parkinson's Disease Brain Bank (UKPDSBB) criteria
• Patients with stable anti-parkinsonian treatment for at least 4 weeks prior to inclusion
• Patients with a Montreal Cognitive Assessment (MoCA) score > 25
• Patients with a Hospital Anxiety and Depression Scale (HADS)-D score ≥ 11
• Person affiliated or benefiting from a social security scheme.
• Free, informed and written consent signed by the participant and the investigator (at the latest on the day of inclusion and before any examination required by the research).

• For patients with pain
• Patients with PD-related central pain defined according to the criteria of Marques et al, 2019
• Patients with chronic central pain (i.e. present for at least 3 months)
• Patients who have average pain over the previous month according to a VAS ≥ 4.

• For patients without pain
• Patients who do not have pain defined as VAS ≤ 4, meaning that it does not interfere with daily activity.

Exclusion criteria

• Patients treated with second line therapy
• Patients with a history of significant psychiatric pathology according to the investigator
• Patients treated with drugs interacting with 5HT1A receptors in the previous 4 weeks
• Patients with contraindication to MRI
• Patients refusing to be informed of an abnormality discovered during brain imaging
• Patients with dyskinesias judged by the investigator to be disabling for imaging.
• Patients under guardianship or other legal protection, deprived of their liberty by judicial or administrative decision
• Pregnant woman, breastfeeding woman