اثر تحریک مغز عمیق تالاموس فرعی بر درد در بیماری پارکینسون

Painful sensations are common in Parkinson’s disease. In many patients, such sensations correspond to neuropathic pain and could be related to central alterations of pain processing. Subthalamic nuclei deep brain stimulation improves motor function in Parkinson’s disease. Several structures of the basal ganglia are involved in nociceptive function, and deep brain stimulation could thus also modify pain perception in Parkinson’s disease. To test this hypothesis, we compared subjective heat pain thresholds, in deep brain stimulation OFF and ON conditions in 2 groups of Parkinson’s disease patients with or without neuropathic pain. We also compared pain-induced cerebral activations during experimental nociceptive stimulations using H215O positron emission tomography in both deep brain stimulation OFF and ON conditions. Correlation analyses were performed between clinical and neuroimaging results. Deep brain stimulation significantly increased subjective heat pain threshold (from 40.3 ± 4.2 to 41.6 ± 4.3, P = .03) and reduced pain-induced cerebral activity in the somatosensory cortex (BA 40) in patients with pain, whereas it had no effect in pain-free patients. There was a significant negative correlation in the deep brain stimulation OFF condition between pain threshold and pain-induced activity in the insula of patients who were pain free but not in those who had pain. There was a significant positive correlation between deep brain stimulation-induced changes in pain threshold and in pain-induced cerebral activations in the primary somatosensory cortex and insula of painful patients only. These results suggest that subthalamic nuclei deep brain stimulation raised pain thresholds in Parkinson’s disease patients with pain and restored better functioning of the lateral discriminative pain system.

Patients with Parkinson’s disease (PD) often suffer from non-motor symptoms. Several recent epidemiological studies have shown that 70% to 80% of PD patients experienced painful sensations [13] and [38]. Moreover, the prevalence of pain in PD is higher than in the general population [1] and [6]. Patients can experience different types of painful symptoms in PD, and several classifications have been proposed [18] with no definite consensus yet. Based on a physiopathological approach, 2 main different types of PD pains can be considered: nociceptive pain related to motor symptoms (dystonias, painful dyskinesias) as opposed to neuropathic pain (classically described as burning, numbness, tingling) [4]. According to the International Association for the Study of Pain (IASP), neuropathic pain is caused by a lesion or a dysfunction of the somatosensory nervous system, and this is supported in PD by several studies showing abnormal pain thresholds [7], [15], [20] and [43], abnormal neuroimaging activations of nociceptive areas [7], and abnormal amplitude of nociceptive laser-evoked potentials [42] and [46]. High-frequency chronic deep brain stimulation (DBS) of the subthalamic nuclei (STN) is an efficient treatment for motor symptoms of advanced PD [30], [32] and [33] modulating basal ganglia circuitry. As some structures of basal ganglia functional loops, such as striatum and thalamus, are also involved in pain processing, we hypothesized that STN-DBS could also modulate pain perception [9]. The effect of STN-DBS on pain in PD has only been partially evaluated. Few reports mentioned some clinical effect on pain [28], [29] and [36]. Only 2 studies have explored the effect of STN-DBS on pain threshold in PD patients, and both had methodological limitations (ie, lack of double-blind and randomized assessments) [22] and [44]. Thus, the aim of the present study was to evaluate and compare the effect of high-frequency STN-DBS on subjective pain threshold in 2 groups of PD patients with or without central neuropathic pain. We also investigated the effect of STN-DBS on pain-induced cerebral activity using positron emission tomography (PET) because our previous study showed an overactivation of nociceptive areas in PD patients during an experimental pain stimulation that might be modulated by STN-DBS [7].