Expanding the clinical spectrum of STIP1 homology and U-box containing protein 1-associated ataxia

Journal of Neurology - STUB1 has been first associated with autosomal recessive (SCAR16, MIM# 615768) and later with dominant forms of ataxia (SCA48, MIM# 618093). Pathogenic variations in STUB1...     

Levodopa raises objective pain threshold in Parkinson's disease: a RIII reflex study

Background

Patients suffering from Parkinson''s disease (PD) describe painful sensations that could be related to neuropathic pain. Experimental data have indicated the involvement of basal ganglia and dopaminergic pathways in central nociceptive processing.

Aim

The objective of this study was to assess and compare the effect of levodopa on the objective pain threshold in patients with PD and healthy subjects.

Methods

The objective pain threshold was assessed by the nociceptive flexion reflex (RIII) in 13 PD patients and 10 healthy subjects. Patients and healthy subjects were evaluated under two randomised conditions: with levodopa (ON) and without (OFF).

Results

Levodopa significantly increased the RIII threshold of PD patients (6.9 (1.2) mA in the OFF condition vs 8 (1.1) mA in the ON position; p = 0.02). RIII threshold was significantly lower in PD patients than in healthy subjects in the OFF condition (6.9 (1.2) mA vs 9.7 (3.4) mA; p = 0.02). RIII threshold did not change after levodopa administration in healthy subjects.

Conclusion

These results provide evidence of a dopaminergic modulation of objective pain threshold in PD patients. In addition, the decrease in RIII threshold in PD patients, in the OFF condition, compared with controls, confirms the existence of an objective pain perception disturbance in PD.Pain is recognised as a feature of Parkinson''s disease (PD) and is reported by 40–75% of patients with PD.¹ Painful sensations are various (musculoskeletal, neuropathic pain) and may be present at any stage of the disease.^2,3Several anatomical, electrophysiological and pharmacological arguments are in favour of the involvement of the basal ganglia and dopaminergic pathways in central nociceptive processing.⁴There are only a few controversial studies on pain perception in PD. The pain threshold of patients with PD has been found to be lower than, higher than or equal to that of healthy subjects.^5,6,7 Recently, Djaldetti et al have shown that patients with PD have a lower subjective heat pain threshold than healthy subjects.⁸ To our knowledge, the effect of levodopa has only been assessed on the subjective pain threshold. Using two different experimental thermal stimulations (cold pressor test and thermotest with Peltier effect), we have previously shown that acute administration of levodopa significantly raised the subjective pain threshold of patients with PD.^9,10The nociceptive flexion reflex (RIII), a polysynaptic reflex, has been described as a useful tool for objectively investigating the pain threshold and its pharmacological modulation by analgesic drugs in normal subjects.^11,12The primary aim of the present study was to compare the effects of levodopa on objective pain threshold (RIII reflex) in pain free patients with PD and in healthy subjects. A secondary objective was to compare such parameters between these two groups.     

Levodopa modifies pain thresholds in Parkinson's disease patients

OBJECTIVE: To assess levodopa dose effect on pain thresholds in Parkinson's disease (PD) patients using an experimental nociceptive thermal stimulation. PATIENTS AND METHODS: We evaluated pain thresholds in 20 PD patients treated by dopaminergic drugs. We assessed heat and cold pain thresholds by using 2 different methods (method of limits and method of levels), intensity-response curve and tolerance threshold. Each PD patient was evaluated in two conditions: ON (after administration of leovdopa and OFF (after acute levodopa withdrawal). The order was randomized. RESULTS: The mean age of patients was 652+/-9.9 years and the mean duration was 9.3+/-3.3 years. Heat pain thresholds were statistically higher in ON versus OFF condition using both methods (44.1+/-3,6 degrees C versus 42.3+/-3,1 degrees C, method of levels, p=0.02). Cold pain thresholds were statistically higher in ON versus OFF condition only using method of levels (17.9+/-4,4 degrees C versus 19.6+/-4,2 degrees C, p=0.02). Heat pain tolerance was statistically higher in ON versus OFF condition (21.4+/-21.6 seconds versus 14.7+/-20.3 seconds, p=0.02). CONCLUSION: This study showed that levodopa increased heat and cold pain thresholds and heat pain tolrance in PD patients. This suggests that dopaminergic drugs could have an analgesic effects on PD related pain.     

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

BackgroundPatients 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.MethodsPain thresholds were determined using a cold pressor test in the two conditions. We used H₂¹⁵O 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.ResultsPain 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 (F _1,16 = 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.ConclusionLevodopa 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.