Nociceptive brain activation in patients with neuropathic pain related to Parkinson's disease

Patients suffering from Parkinson's disease (PD) frequently experience painful sensations that may be due to central modification of nociception in PD. We compared pain thresholds and cerebral activity in nociceptive areas using Positron Emission Tomography (PET) during nociceptive stimulation before (OFF condition) and after (ON condition) levodopa challenge between nine PD patients with and nine PD patients without neuropathic pain.

Pain thresholds were determined using a cold pressor test in the two conditions. We used H2(15)O PET to study the regional cerebral blood flow changes in subjects while they received alternate randomized noxious and innocuous cold stimuli during OFF and ON periods.

Pain thresholds were not significantly different between PD patients with and without pain in either condition (OFF and ON). In both groups of PD patients, levodopa significantly raised pain threshold (F1,16 = 26.71; p < 0.0001) with a mean variation of -2.7 (±2.3 °C). In the OFF condition, PD patients with pain had a lower pain activation in the right prefrontal cortex and posterior insula and a higher pain activation in the right anterior cingulate cortex (BA32/8) than pain-free patients. Levodopa significantly reduced pain-induced-activation in the right insula and in the anterior cingulate cortex in both groups.

Levodopa decreased nociceptive perception in both PD patients with and without pain. In PD patients with neuropathic pain the medial affective pathway was preferentially recruited whereas pain-free PD patients exhibited a greater activation in lateral discriminative nociceptive areas.