Apomorphine Effect on Nociceptive Perception in Parkinson's: a Clinical and Imaging Study

Patients suffering from Parkinson's disease (PD) frequently experienced painful sensations. Painful complaints with various description (muscle cramps, painful dystonia, aching, numbness, tingling, burning, vibrating, lancinating) are described and can or cannot be related to motor symptoms. Physiopathology of pain in PD is discussed. It has been suggested that the occurrence of painful symptoms could be in part due to central modification of nociception and basal ganglia damage and the dopaminergic deficit would be expected to eliminate the inhibitory influence on thalamic nociceptive activity. Recently, data have shown that PD patient had a lower nociceptive threshold than healthy volunteers. Our team has reported that levodopa administration normalised this nociceptive threshold and decreased cerebral activity measured with positrons emission tomography (PET- H215O during experimental nociceptive stimulation) in several nociceptive cortical areas which were overactive in PD. These findings suggest that central dopamine system plays an important part in the control of the nociceptive pathways in PD. Nevertheless, in the central nervous system, levodopa could be converted in dopamine but also in noradrenaline modulating noradrenergic system. In order to confirm the involvement of dopaminergic system in nociceptive processing in PD, we would like to assess a specific drug of dopamine system (a dopamine agonist, apomorphine) in PD patients.

The primary objective of this study is to assess the effect of dopamine agonist acute administration versus placebo on the nociceptive subjective threshold in two groups of PD patients (painful PD patients, n =16 and pain free PD patients, n = 16). This is a controlled cross over, double blind, randomised study.

The secondary objectives are to assess and to compare the apomorphine effect on the objective nociceptive threshold (nociceptive flexion reflex) and on the activation of cerebral areas using functional imaging (TEP- H215O) during experimental nociceptive stimulation in the two groups of PD patients.

Inclusion criteria

• Patients suffering from Parkinson's disease
• PD patients with a Hoehn et Yahr < à 3 (Hoehn et Yahr 1967)
• PD patients treated by dopaminergic drugs (levodopa, dopamine agonist, IMAO-B, ICOMT…)
• Painful PD patients : PD patients suffering from chronic pain (> 3 months) which is related to PD and suggests neuropathic pain
• Pain free PD patients : PD patients without any pain related to PD.

Exclusion criteria

• Patients with chronic disease resulting in chronic pain (severe arthosis….)
• PD patients with a Hoehn et Yahr stage > 3 (Hoehn et Yahr 1967)
• Patients with cancer
• Patients who underwent a PET scan in the last three months
• Pregnancy
• Patients with a contra indication of use of apomorphine or domperidone.