Central pain modulation after subthalamic nucleus stimulation A crossover randomized trial

Objective: To investigate the acute effect of subthalamic nuclei deep brain stimulation (STN-DBS) and levodopa on pain and tolerance thresholds in patients with Parkinson disease. We hypothesized that a modification of pain threshold after STN-DBS would suggest a central modification of pain perception, whereas the absence of pain threshold change after STN-DBS would correspond to a peripheral mechanism via a decrease of painful stimuli. Methods: Nineteen patients with Parkinson disease were included in this double-blind, randomized, crossover study. Postoperatively, we evaluated pain thresholds (thermal and mechanical) and motor symptoms under 3 acute conditions: stimulation on/medication off; stimulation off/medication on; and stimulation off/medication off. We also conducted a retrospective analysis of the data prospectively recorded during the follow-up of the cohort pre- and postoperatively (Unified Parkinson's Disease Rating Scale [UPDRS] score, Hoehn and Yahr stage, equivalent levodopa daily dose, and tapping test score). Results: We found a significant increase of pain and tolerance mechanical thresholds not only after acute STN-DBS but also after acute levodopa administration. We did not find any significant correlation between postoperative clinical pain improvement and UPDRS-III improvement after acute levodopa or STN-DBS, nor with motor complications improvement assessed with UPDRS-IV after chronic STN-DBS. No correlation was found between postoperative clinical pain improvement and mechanical pain threshold modification. Conclusion: Clinical pain alleviation after STN-DBS cannot be considered merely as a consequence of motor complications improvement and could be attributable to a direct central modulation of pain perception, via increased mechanical pain and tolerance thresholds.